Integrating Biology and Phytochemistry to Identify Antiparasitic Natural Products from Gardenia imperialis K. Schum (Rubiaceae)

Integrating Biology and Phytochemistry to Identify Antiparasitic Natural Products from Gardenia imperialis K. 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Schum (Rubiaceae) Christelle Wayoue Kom, Sylvester Osei Bobbie, Darline Dize, Mariscal Brice Tchatat Tali, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8460808/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Gardenia imperialis is used in Cameroonian traditional medicine to treat malaria and related symptoms. This study aimed to conduct a phytochemical investigation of G. imperialis extracts through bioassay-guided fractionation to identify anti-parasitic compounds. Methods Crude methanolic extracts from the leaves and stem bark were subjected to bioassay-guided fractionation using liquid chromatography–mass spectrometry (LC–MS) and preparative high-performance liquid chromatography (HPLC). The structures of isolated natural products were elucidated by spectroscopic analysis, including NMR and MS. All extracts, fractions, subfractions, and pure compounds were evaluated for cytotoxicity against Vero and Raw264.7 cell lines and for anti-parasitic activity against Plasmodium falciparum (Dd2 and 3D7 strains), Trypanosoma brucei brucei , and Leishmania donovani . Results The leaf methanolic extract (GIlMeOH) exhibited broad-spectrum anti-parasitic activity (IC₅₀ < 11 µg/mL) without cytotoxicity towards mammalian cell lines. Dereplication and isolation yielded fractions, subfractions, and compounds with improved activity (IC₅₀ values ranging from 0.67 to 37.2 µg/mL). Among the isolated compounds, gradenin A, salvigenin, hispidulin, and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone showed potent antitrypanosomal activity with IC₅₀ values of 2.8, 2.5, 16.6, and 9.7 µg/mL, respectively. The anti-parasitic activities of gradenin A, salvigenin, and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone are reported here for the first time. Conclusion The promising anti-parasitic profile of the G. imperialis leaf extract and its isolated constituents, particularly and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone, gradenin A, and salvigenin, supports further investigation into their potential as novel and selective agents against parasitic diseases. Parasitology Gardenia imperialis Antiparasitic activity Plasmodium falciparum Leishmania donovani Trypanosoma brucei brucei Natural roducts Figures Figure 1 Figure 2 1. Background Malaria, Human African Trypanosomiasis (HAT), and leishmaniasis remain infectious diseases of significant public health concern, with a cumulative estimate of hundreds of millions of cases annually [ 1 – 3 ]. Malaria is a complex disease caused by protozoan parasites of the Plasmodium genus, which progress through multiple life stages, evading host immune responses and complicating treatment. Similarly, leishmaniasis (visceral and cutaneous) and trypanosomiasis are caused by various species of the Leishmania and Trypanosoma genera, respectively. Current therapies for these parasitic diseases are often inadequate, plagued by issues such as toxicity, complex administration regimens, and the increasing spread of drug resistance [ 4 – 6 ]. Consequently, there is an urgent need for new drug leads with novel mechanisms of action. Natural products, informed by ethnopharmacological knowledge, represent a vital source for such new chemical entities [ 7 ]. The structural diversity of plant-derived metabolites can help renew the therapeutic arsenal in the continuous fight against resistance. The rich biodiversity of medicinal plants, combined with traditional use, continues to offer promising avenues for drug discovery, as exemplified by the historical success of quinine from Cinchona species and artemisinin from Artemisia annua [ 8 ]. Gardenia imperialis K. Schum (Rubiaceae) is a plant used in the traditional Cameroonian pharmacopoeia for the treatment of malaria and related symptoms. The genus Gardenia is known to produce a wide array of biologically active and structurally diverse secondary metabolites [ 9 ]. Therefore, this study was undertaken to perform a bioactivity-guided phytochemical investigation of G. imperialis using chromatographic and spectroscopic techniques, evaluating the extracts and isolated compounds against Plasmodium falciparum , Leishmania donovani , and Trypanosoma brucei brucei . 2. Methods 2.1 Plant Material Leaves and stem bark of Gardenia imperialis K. Schum were collected in Sangmelima, Cameroon (2.9333° N, 11.9833° E), in August 2021. A voucher specimen (ID 58234/HNC) was deposited at the National Herbarium of Cameroon for identification. 2.2 Extraction The plant materials were washed, air-dried in the shade, and pulverized. Powdered leaves and stem bark (500 g each) were macerated in 5 L of methanol for 72 h at room temperature. The extracts were filtered, and the filtrates were concentrated under reduced pressure at 50°C using a rotary evaporator. The resulting crude methanolic extracts from the leaves (GIlMeOH) and stem bark (GIsbMeOH) were stored at 4°C for subsequent bioactivity assays. 2.3 Bioassay-Guided Fractionation and Isolation Preliminary antiparasitic screening identified the leaf extract (GIlMeOH) as the most active. Consequently, 78.6 g of GIlMeOH was subjected to flash chromatography [ 10 ] on silica gel (0.063–0.2 mm) eluted with a stepwise gradient of n -hexane-EtOAc (100:0 to 50:50, v/v), followed by methanol, to yield six major fractions (GI1–GI6). Fractions GI3, GI5, and GI6, which showed significant antiparasitic activity, were selected for further investigation. These were analyzed by LC–MS-Q-TOF, and the data were processed using the Global Natural Products Social (GNPS) molecular networking platform for dereplication. The fractions were subsequently purified by Medium/High Pressure Liquid Chromatography (M/HPLC). Fraction GI3 yielded four known flavonoids, while GI5 afforded one flavonoid. The structures of all isolated compounds were elucidated by extensive 1 H and 13 C NMR spectroscopy (Supplementary Information 1). 2.4 Antiparasitic Assays 2.4.1 Parasite Cultures Plasmodium falciparum strains 3D7 (chloroquine-sensitive) and Dd2 (multidrug-resistant) were maintained in human O + erythrocytes at 4% hematocrit in complete RPMI 1640 medium (supplemented with 0.5% Albumax II, 25 mM HEPES, and 0.04% gentamicin) at 37°C under a 5% CO₂ atmosphere [ 5 ]. Leishmania donovani (strain 1S) promastigotes were cultured at 28°C in M199 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 1% penicillin/streptomycin. Trypanosoma brucei brucei (bloodstream form, strain Lister 427) was cultivated at 37°C under 5% CO₂ in HMI-9 medium supplemented with 10% FBS. 2.4.2 Sample Preparation Stock solutions of extracts, fractions, and isolated compounds (100 mg/mL) and reference drugs were prepared in DMSO. Working concentrations were prepared by serial dilution in the respective culture media, ensuring the final DMSO concentration did not exceed 0.1%. 2.4.3 Antiplasmodial Assay Anti- Plasmodium activity was evaluated against synchronized ring-stage cultures [ 11 ] of P. falciparum (3D7 and Dd2) using the SYBR Green I fluorescence method [ 12 ]. Parasites (1% parasitemia, 2% hematocrit) were incubated with test samples for 72 h. Artemisinin and chloroquine (10 µM) served as positive controls, while 0.1% DMSO was the negative control. After lysis with SYBR Green I buffer, fluorescence was measured (excitation/emission: 485/530 nm). The half-maximal inhibitory concentration (IC₅₀) was determined from dose-response curves. 2.4.4 Antileishmanial and Antitrypanosomal Assays Activity against L. donovani promastigotes and T. b. brucei trypomastigotes was assessed using a resazurin-based assay [ 13 , 14 ]. Parasites were incubated with test samples for 24 h ( L. donovani ) or 68 h ( T. b. brucei ), after which resazurin solution was added. Following further incubation, fluorescence was measured (excitation/emission: 530/590 nm). Amphotericin B and pentamidine were used as positive controls for Leishmania and Trypanosoma , respectively. 2.5 Cytotoxicity Assay Cytotoxicity against mammalian Vero (ATCC® CRL-1586) and Raw264.7 (ATCC® TIB-71) cell lines was determined using a resazurin assay [ 14 ]. Cells were seeded at 1 × 10⁴ cells/well, allowed to adhere, and then treated with samples for 48 h. Resazurin was added, and after 4 h, fluorescence was measured. The half-maximal cytotoxic concentration (CC₅₀) was calculated. The selectivity index (SI) was defined as SI = CC₅₀ (mammalian cells) / IC₅₀ (parasites). 2.6 Data Analysis All experiments were performed in duplicate and independently repeated twice. Dose-response curves were plotted using GraphPad Prism 8.0, and IC₅₀/CC₅₀ values were derived by nonlinear regression. Data processing was performed using Microsoft Excel. 3. Results 3.1 Bioassay-Guided Fractionation and Identification of Compounds Initial screening of the methanolic extracts from Gardenia imperialis revealed that the leaf extract (GIlMeOH) exhibited potent and broad-spectrum antiparasitic activity with IC 50 values ranging from 5.5 to 10.7 µg/mL and good selectivity (SI > 9) (Table 3 ). It was consequently selected for bioassay-guided fractionation. Fractionation of GIlMeOH by flash chromatography yielded several fractions, of which GI3, GI5, and GI6 showed significant activity. The GI3 fraction (eluted with n -hexane-EtOAc, 80:20) was particularly active against P. falciparum Dd2 (IC₅₀ = 6.9 µg/mL) and T. b. brucei (IC₅₀ = 4.8 µg/mL) and was therefore subjected to further purification. Subsequent HPLC separation and spectroscopic analysis of fraction GI3 (Fig. 1 ) led to the isolation and identification of four flavonoids (Fig. 2 , Tables 1 & 2 ). The structures of these compounds were established as hispidulin ( 1 ), 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone ( 2 ), gradenin A ( 3 ), and salvigenin ( 4 ) based on 1 H and 13 C NMR and MS data (Supplementary Information). The 1 \(\:H\) and 13 \(\:C\) NMR data for these compounds are summarized in Tables 1 & 2 . Compound 5,7,3’,trihydroxy-6-4’5’-trimethoxyflavone along with 6 subfractions (GI3.2f, GI3.2 g, GI3.2 h, GI3.2i, GI3.3a, and GI3.3g) exhibited a broad-spectrum antiparasitic activity with IC 50 values ranging from 0.6 µg/mL to 23.9 µg/mL and good selectivity. Salvogenin, gradenin A, and hispidulin potently inhibited T. b. brucei with IC 50 values of 2.5 µg/mL, 2.8 µg/mL, and 15.6 µg/mL, respectively. Fractionation of fraction GI5 led to one inactive flavonoid, cirsimaritin ( 5 ) (Fig. 2 ). Table 1 1 H NMR data for compounds (1–5) compared with literature data. Hispidulin 1 Flavone 2 Gradenin A 3 Savigenin 4 Cirsimaritin 5 6.61 6.59 12.99 12.98 7.09 7.09 12.76 12.77 12.76 12.76 6.79 6.77 10.70 10.76 6.61 6.63 7.84 7.85 7.86 7.86 7.93 7.93 9.60 9.63 6.56 6.57 7.02 7.02 6.92 6.92 6.93 6.93 7.17 7.16 3.94 3.93 6.54 6.56 6.60 6.61 3.76 3.75 6.92 6.91 3.97 3.97 6.58 6.60 6.52 6.52 13.09 13.07 6.60 6.59 3.99 3.99 3.97 3.98 3.92 3.91 10.5 10.5 3.80 3.88 3.92 3.93 3.87 3.87 3.70 3.75 3.89 3.90 Table 2 13 C NMR data for compounds (1–5) compared with literature data. Hispidulin 1 Flavone 2 Gradenin A 3 Salvigenin 4 Cirsimaritin 5 182.1 182.1 182.2 182.3 182.6 182.6 182.5 182.7 182.1 182.2 163.7 163.8 165.3 163.3 163.8 163.9 163.8 164.1 163.8 163.7 161.2 161.2 153.6 153.6 158.9 158.9 162.4 162.6 161.2 161.1 157.7 157.3 152.8 152.5 153.7 153.6 158.6 158.7 158.9 158.9 152.7 152.8 150.9 150.9 153.2 153.2 152.9 153.7 152.7 152.7 152.4 152.4 139.6 139.7 153.1 153.0 127.9 128.0 152.4 152.5 131.3 131.4 125.9 125.9 141.6 141.4 123.5 123.5 131.3 131.1 121.1 121.2 107.7 107.7 132.9 132.7 114.4 114.5 128.4 128.4 103.9 104.0 104.2 104.2 126.5 126.5 104.1 104.1 121.2 121.2 128.4 128.5 102.1 102.2 106.3 106.2 90.5 90.5 115.9 115.8 115.9 115.9 60.1 60.1 105.4 105.4 60.5 60.9 104.1 104.0 94.2 94.2 59.9 59.9 103.9 103.7 56.3 56.3 102.4 102.4 102.3 102.3 56.2 56.2 90.7 90.7 55.6 55.5 94.3 94.2 59.7 59.9 157.5 157.5 61.0 61.1 59.9 59.9 152.5 152.5 60.8 60.9 56.4 56.4 56.5 56.4 56.4 56.4 3.2. Experimental Section Hispidulin ( 1 ): Yellow compound. 1 H and 13 C NMR spectra (DMSO- d 6 ), see Tables 2 and 3 ; (+)-HRESIMS: m/z [M + H] + calc. for C 16 H 12 O 6 301.0700 (calcd for C 16 H 12 O 6, 301.0634; Δ3.47ppm) calc. [M + Na] 323.0516, 5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone ( 2 ): Yellow powder, 1 H and 13 C NMR spectra (DMSO- d 6 ), see Tables 2 and 3 ; (+)-HRESIMS: m/z [M + H] + calc. for C 18 H 16 O 8 361.0895 (calcd for C 18 H 16 O 8, 361.0923; Δ1.36ppm), calc. [M + Na] 383.0703. Gradenin A ( 3 ): White powder, 1 H and 13 C NMR spectra (DMSO- d 6 ), see Tables 2 and 3 ; (+)-HRESIMS: m/z [M + H] + calc. for C 20 H 20 O 8 389.1215 (calcd for C 20 H 20 O 8, 389.1236; Δ2.40ppm), calc. [M + Na] 411.1034. Salvigenin ( 4 ): White powder, 1 H and 13 C NMR spectra (CDCl 3 ), see Tables 2 and 3 ; (+)-HRESIMS: m/z [M + H] + calc. for C 18 H 16 O 6 329.1028 (calcd for C 18 H 16 O 6, 329.1025; Δ0.91ppm), calc. [M + Na] 351.0849. Cirsimaritin ( 5 ): White powder, 1 H and 13 C NMR spectra (CDCl 3 ), see Tables 2 and 3 ; (+)-HRESIMS: m/z [M + H] + calc. for C 17 H 14 O 6 315.0872 (calcd for C 17 H 14 O 6, 315.0868; Δ1.27ppm), calc. [M + Na] 337.0689. Table 3 Antiparasitic activity and selectivity of Gardenia imperialis extracts, fractions, and compounds Codes Vero/Raw264.7 Cells P. falciparum IC50 (µg/mL) ± SD Kinetoplastids IC50 (µg/mL) ± SD Crude extracts CC50 (µg/mL) ± SD Pf Dd2 SIVero/Dd2 Pf 3D7 SIVero/3D7 RI L. donovani SIRaw264.7 T. b. brucei SIVero GIsbMeOH > 100 18.9 ± 4.4 > 5.3 32.1 ± 4.5 > 3.1 0.6 > 50 > 50 GIlMeOH > 100 5.5 ± 0.0 > 18.2 8.1 ± 1.2 > 12.3 0.7 10.7 ± 0.2 > 9.3 9.4 ± 0.4 > 10.6 Fractions GI3:Hex- EtOAc (80:20) > 100 6.9 ± 0.4 > 14.5 > 50 ND > 50 4.8 ± 0.3 > 20.8 Subfractions/compounds GI3.2a (Gradenin A) > 100 > 50 > 50 ND > 50 2.8 ± 0.3 > 35.7 GI3.2b (Salvigenin) > 100 > 50 > 50 ND > 50 2.5 ± 0.2 > 40 GI3.2c (Hispidulin) > 100 23.8 ± 2.7 > 4.2 > 50 23.2 15.6 ± 1.2 > 6.4 GI3.2d (5,7,3’-Trihydroxy-6-4’,5’-trimethoxyflavone) > 100 20.2 ± 3.4 > 4.9 20.4 ± 3.2 > 4.9 1 9.7 ± 0.05 > 10.3 9.7 ± 0.4 > 10.4 G31.2e > 100 22.9 ± 0.6 > 4.4 > 50 16.1 8.2 ± 0.3 > 12.2 GI3.2f > 100 9.2 ± 0.6 > 10.9 18.4 ± 2.2 > 5.4 0.5 2.8 ± 0.10 > 35.7 9.9 ± 0.05 > 10.1 GI3.2 g > 100 4.9 ± 0.4 > 20.4 6.8 ± 0.1 0.7 8.0 ± 0.12 > 12.5 1.5 ± 0.5 > 66.7 GI3.2 h > 100 4.7 ± 0.1 > 21.3 9.0 ± 0.6 > 11.1 0.5 11.5 ± 0.23 > 8.7 1.3 ± 0.2 > 76.9 GI3.2i > 100 10.7 ± 0.9 > 9.3 23.9 ± 0.0 > 4.2 0.4 3.0 ± 0.10 > 33.3 12.0 ± 2.3 > 8.3 GI3.2j > 100 14.1 ± 0.8 > 7.1 > 50 50 21.2 ± 0.4 > 4.7 GI3.2k > 100 7.0 ± 0.1 > 14.3 24.9 ± 0.0 > 4 0.3 > 50 13.7 ± 2.0 > 7.3 GI3.2 l > 100 16.4 ± 0.3 > 6.1 > 50 50 23.4 ± 1.2 > 4.3 GI3.3a > 100 11.4 ± 0.4 > 8.8 14.5 ± 0.3 > 6.9 0.8 6.7 > 14.9 8.4 ± 0.18 > 11.9 GI3.3b > 100 24.0 ± 0.0 > 4.2 > 50 50 5.3 ± 07 > 18.9 GI3.3c > 100 23.4 ± 0.3 > 4.3 > 50 50 5.5 ± 7 > 18.2 GI3.3d > 100 14.6 ± 0.9 > 6.8 12.0 ± 0.6 > 8.3 1.2 > 50 4.8 ± 0.67 > 20.8 GI3.3e > 100 11.9 ± 0.1 > 8.4 17.0 ± 1.8 > 5.9 0.7 > 50 2.2 ± 0.4 > 45.4 GI3.3 f > 100 17.8 ± 0.7 > 5.6 > 50 50 1.1 ± 0.17 > 90.9 GI3.3 g > 100 13.0 ± 0.1 > 7.7 21.4 ± 0.3 > 4.7 0.6 9.1 ± 0.03 > 11 0.6 ± 0.0 > 166.7 GI3.3h > 100 14.7 ± 0.0 > 6.8 13.7 ± 0.8 > 7.3 1.1 > 50 3.0 ± 0.9 > 33.3 GI5: Hex- EtOAc (1:1) > 100 18.1 ± 0.1 > 5.5 > 50 ND > 50 > 50 GI5.1 > 100 > 50 > 50 ND > 50 > 50 GI5.2 > 100 11.4 ± 2.2 > 8.8 > 50 ND > 50 5.8 ± 0.1 > 17.2 GI5.3 > 100 > 50 > 50 ND > 50 4.8 ± 0.6 > 20.8 GI5.4 (Cirsimaritin) > 100 > 50 > 50 ND > 50 > 50 GI5.5 > 100 9.1 ± 0.8 > 11 > 50 > 15.9 > 50 > 50 GI6: Residue (MeOH) > 100 37.2 ± 1.5 > 2.7 > 50 ND > 50 > 50 Reference drugs Artemisinin (µM) ND 0.03 ± 0.0 0.04 ± 0.0 0.7 ND ND Chloroquine (µM) ND 0.70 ± 0.2 0.03 ± 0.0 22.6 ND ND Amphotericin B (µM) ND ND ND ND 0.02 ± 0.0 ND Pentamidine (µM) ND ND ND ND ND 0.006 ± 0.0 Podophyllotoxin (µM) 0.19 ± 0.01 ND ND ND ND ND IC 50 : 50% inhibitory concentration; CC 50 : 50% cytotoxic concentration; Activity values were derived for sigmoidal dose-response curves fitted by non-linear regression using GraphPad Prism 8.0 software; SD: standard deviation; Plant samples were tested in triplicate experiments against parasites in normal culture conditions; GIsbMeOH: Methanolic extract from stem bark of G. imperialis ; GIlMeOH: Methanolic extract from leaves of G. imperialis ; RI: Resistance index = IC 50 Pf Dd2/IC 50 Pf 3D7; SIVero: Selectivity index when tested on Vero cells; SIRaw264.7: Selectivity index when tested on Raw264.7 cells. 4. Discussion This study provides the first comprehensive report on the antiparasitic properties of Gardenia imperialis . While the fractionation process successfully concentrated the antitrypanosomal activity, it did not significantly enhance the potency against Plasmodium or Leishmania compared to the crude leaf extract (GIlMeOH). A key finding was that all active samples, including the crude extract, fractions, and isolated compounds, demonstrated an antiplasmodial resistance index (RI) of less than 1. This indicates a consistent and promising preferential inhibition of the multidrug-resistant P. falciparum Dd2 strain over the sensitive 3D7 strain. The observed antiplasmodial activity aligns with previous studies on other Gardenia species. Extracts from G. sokotensis , G. lutea , G. ternifolia , and G. saxatilis have all shown activity against various Plasmodium strains [ 15 – 17 ], supporting the genus as a source of anti-malarial compounds. Previous phytochemical investigations of these species have identified flavonoids and triterpenoids [ 17 ], compound classes consistent with our findings. Our bioassay-guided approach led to the isolation of several flavonoids. Among them, hispidulin confirmed its known broad-spectrum antiprotozoal potential, showing activity against all three parasites tested [ 18 , 19 ]. The most significant contributions of this work, however, are the first reports of antiparasitic activity for three compounds: gradenin A, salvigenin, and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone. Notably, gradenin A and salvigenin exhibited potent antitrypanosomal activity (IC₅₀ = 2.8 and 2.5 µg/mL, respectively). While salvigenin is known for its anti-inflammatory, analgesic, and anticancer properties [ 20 , 21 ], its activity against T. b. brucei is described here for the first time. In contrast, gradenin A appears to be a largely unexplored natural product. It is listed in the ChEMBL database (CHEMBL485823) but, to the best of our knowledge, no biological activity has been previously reported. Its potent antitrypanosomal activity identified in this study positions it as a promising novel scaffold for future investigation. Similarly, the broad-spectrum antiparasitic activity of 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone against P. falciparum , L. donovani , and T. b. brucei is reported here for the first time. Its structural similarity to other bioactive trimethoxyflavones [ 22 ] suggests a potential mechanism of action worthy of further exploration. 5. Conclusion This bioactivity-guided investigation of Gardenia imperialis validates its traditional use and identifies its leaves as a source of potent antiparasitic compounds. The study successfully isolated several flavonoids, with the antitrypanosomal activities of gradenin A and salvigenin being particularly notable. Furthermore, the broad-spectrum activity of 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone against Plasmodium falciparum , Leishmania donovani , and Trypanosoma brucei brucei is reported here for the first time. The consistent preference for inhibiting the multidrug-resistant P. falciparum Dd2 strain is another promising finding. These results warrant further investigation into these natural products as novel and selective lead compounds for the development of new treatments for malaria and neglected tropical diseases. Abbreviations ACT : Artemisinin-based Combination Therapy; ATCC : American Type Culture Collection; BEI Resources : Biodefense and Emerging Infections Research Resources Repository; CC 50 : 50% Cytotoxic Concentration; DMEM : Dulbecco’s Modified Eagle’s Medium; DMSO : DiMethylSulfOxyde; EDTA : Tetracyclic Ethylene Diamine; FBS : Fœtal Bovin Serum; HEPES : 4-(2-hydroxyethyl) -1-piperazineethanesulfonic acid; Hex : hexane; IC 50 : 50% Inhibitory Concentration; MeOH : Methanol; NMR : Nuclear Magnetic Resonance Spectrometer; P. falciparum : Plasmodium falciparum ; Pf 3D7 : Plasmodium falciparum 3D7 Pf Dd2 : Plasmodium falciparum Dd2; RPMI 1640 : Roswell Park Memorial Institute 1640; SD : Standard Deviation; SI : Selectivity index (CC 50 /IC 50 ); SIRaw264.7 : Selective Index for Raw264.7 cells; SIVero : Selective Index for Vero cells; GIsbMeOH: Methanolic extract from stem bark of G. imperialis ; GIlMeOH: Methanolic extract from leaves of G. imperialis ; RI: Resistance index = IC 50 Pf Dd2/IC 50 Pf 3D7. Declarations Data Availability All data generated or analysed during this study are included in this published article and its supplementary information file. Funding and/or Competing interests Funding The authors did not receive support from any organization for the submitted work. Competing interest The authors have no competing interests to declare that are relevant to the content of this article. Authors’ contributions Christelle Wayoue Kom: Investigation, Methodology, Software, Visualization, Validation, Writing – original draft, Writing – review & editing; Sylvester Osei Bobbie: Investigation, Methodology, Writing – review & editing; Darline Dize: Investigation, Methodology, Writing – review & editing; Mariscal Brice Tchatat Tali: Investigation, Methodology, Validation, review & editing; Cyrille A.N. Ngansop: Investigation, Methodology, Software; Lauve R.T. Yamthe: Methodology, Writing – review & editing; Bill Baker: Validation, Supervision, Writing – review & editing; Fabrice Fekam Boyom: Conceptualization, Funding acquisition, Validation, Supervision, Writing – review & Editing. All the authors approved the final version of the manuscript Acknowledgments The authors would like to express their gratitude to BEI Resources (https://www.beiresources.org/) for providing the parasitic strains and to the Department of Chemistry at the University of South Florida, Tampa, USA, for their assistance with compound identification. They also acknowledge the valuable contribution of the Cameroon National Herbarium, Yaounde, for plant identification. References Priya V. WHO world malaria report 2024. Lancet Microbe . 2024;6(4):101073. Roy S, Chancey R, Cantey P, Straily A. Trypanosomiasis, African. CDC Yellow Book . 2024. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2024/infectious-diseases/trypanosomiasis-african. World Health Organization. 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Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob Agents Chemother . 2004;48:1803–1806. https://doi.org/10.1128/AAC.48.5.1803. Siqueira-Neto JL, Song OR, Oh H, Sohn JH, Yang G, et al. Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds. PLoS Negl Trop Dis . 2010;4(5):e675. doi:10.1371/journal.pntd.0000675. Bowling T, Mercer L, Don R, Jacobs R, Nare B. Application of a resazurin-based high-throughput screening assay for the identification and progression of new treatments for human African trypanosomiasis. Int J Parasitol Drugs Drug Resist . 2012;2:262–270. Jansen O, Angenot L, Tits M, Nicolas JP, De Mol P, Nikiema JB, Frederich M. Evaluation of 13 selected medicinal plants from Burkina Faso for their antiplasmodial properties. J Ethnopharmacol . 2010;130(1):143–150. El Tahir A, Satti GMH, Khalid SA. Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on Maytenus senegalensis (Lam.) Exell. J Ethnopharmacol . 1999;64:227–233. Suksamrarn A, Tanachatchairatana T, Kanokmedhakul S. Antiplasmodial triterpenes from twigs of Gardenia saxatilis . J Ethnopharmacol . 2003;88:275–277. Sülsen VP, Cazorla SI, Frank FM, Redko FC, Anesini CA, Coussio JD, Malchiodi EL, Martino VS, Mischietti LV. Trypanocidal and leishmanicidal activities of flavonoids from Argentine medicinal plants. Am J Trop Med Hyg . 2007;77:654–659. Grecco Sdos S, Felix MJ, Lago JH, Pinto GE, Tempone AG, Romoff P, Ferreira JMP, Sartorelli P. Anti-trypanosomal phenolic derivatives from Baccharis uncinella . Nat Prod Commun . 2014;9:171–173. Mansourabadi AM, Sadeghi HM, Razavi N, Rezvani E. Anti-inflammatory and analgesic properties of salvigenin, a Salvia officinalis flavonoid extract. Adv Herbal Med . 2015;1:31–41. Mansourizadeh F, Houri Sepehri, Khoee S, Farimani MM, Delphi L, Tousi MS. Designing salvigenin-loaded mPEG-b-PLGA@Fe₃O₄ nanoparticles for enhanced anti-cancer effects on breast cancer cells: an in vitro study. J Drug Deliv Sci Technol . 2020;57:101619. https://doi.org/10.1016/j.jddst.2020.101619. Tang J, Wang W, Luan F, Chen X. Binding of the bioactive compound 5,7,4′-trihydroxy-6,3′,5′-trimethoxyflavone to human serum albumin. Int J Biol Macromol . 2005;37(1–2):85–91. doi:10.1016/j.ijbiomac.2005.08.010. Additional Declarations The authors declare no competing interests. Supplementary Files SupplementaryinformationGardeniams.docx Supplementary data The supplementary information (Suppl. 1) includes chromatographic and spectroscopic data for all compounds identified in this study. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8460808","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":566155696,"identity":"2fbfcbd3-fc09-4533-a3e0-02dc3951b8c9","order_by":0,"name":"Christelle Wayoue Kom","email":"","orcid":"","institution":"University of Yaounde 1","correspondingAuthor":false,"prefix":"","firstName":"Christelle","middleName":"Wayoue","lastName":"Kom","suffix":""},{"id":566155697,"identity":"016d9495-0455-4fc6-99e1-9da3b188a8e5","order_by":1,"name":"Sylvester Osei Bobbie","email":"","orcid":"","institution":"University of South Florida, 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13:45:28","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":139464,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8460808/v1/349e16ba12d1a444071f2d91.html"},{"id":99796274,"identity":"95d141a7-564d-4c9d-bbde-70c8cca14b80","added_by":"auto","created_at":"2026-01-08 13:40:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":374020,"visible":true,"origin":"","legend":"\u003cp\u003eHigh Pressure Liquid Chromatography (HPLC) of GI3. HPLC conditions: Solvent water (A) Acetonitrile (B). Gradient: 0 to 4 mins 10%B; 32mins 100%B; 36mins 100%B; 40mins 10%B; Wavelength: 254 and 280 nm; Flow rate: 4ml/min, Column: Luna 5u C18(2) 100A 250 x 10.00mm, 5 micron. Numbers shown indicate the pooling of fractions into 15 sub fractions.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8460808/v1/7ced436233ea53f9163f164b.png"},{"id":99716695,"identity":"ff5810a0-9055-403a-8065-77953889c7f8","added_by":"auto","created_at":"2026-01-07 14:43:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49957,"visible":true,"origin":"","legend":"\u003cp\u003eFlavonoids found in \u003cem\u003eGardenia imperialis\u003c/em\u003e from Cameroon, Africa.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8460808/v1/e76a121aaa7ad07942680736.png"},{"id":99805147,"identity":"0e93e128-9d04-45c5-873c-9a6d14409722","added_by":"auto","created_at":"2026-01-08 14:15:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1747975,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8460808/v1/74f7633d-09d7-4317-8762-7e5649b666f8.pdf"},{"id":99716706,"identity":"ac8ea4ae-b54b-465d-ac73-0d5cc7b92e52","added_by":"auto","created_at":"2026-01-07 14:43:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3713957,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe supplementary information (Suppl. 1) includes chromatographic and spectroscopic data for all compounds identified in this study.\u003c/p\u003e","description":"","filename":"SupplementaryinformationGardeniams.docx","url":"https://assets-eu.researchsquare.com/files/rs-8460808/v1/342c6ebe4ccde62f26670403.docx"},{"id":99796632,"identity":"d82ccb3b-e5b7-4206-b249-ccf5041efd96","added_by":"auto","created_at":"2026-01-08 13:43:01","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":211828,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"GraphicalAbstractGI.tif","url":"https://assets-eu.researchsquare.com/files/rs-8460808/v1/68b5dfd4a14901e9e0872d92.tif"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eIntegrating Biology and Phytochemistry to Identify Antiparasitic Natural Products from \u003cem\u003eGardenia imperialis\u003c/em\u003e K. Schum (Rubiaceae)\u003c/p\u003e","fulltext":[{"header":"1. Background","content":"\u003cp\u003eMalaria, Human African Trypanosomiasis (HAT), and leishmaniasis remain infectious diseases of significant public health concern, with a cumulative estimate of hundreds of millions of cases annually [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Malaria is a complex disease caused by protozoan parasites of the \u003cem\u003ePlasmodium\u003c/em\u003e genus, which progress through multiple life stages, evading host immune responses and complicating treatment. Similarly, leishmaniasis (visceral and cutaneous) and trypanosomiasis are caused by various species of the \u003cem\u003eLeishmania\u003c/em\u003e and \u003cem\u003eTrypanosoma\u003c/em\u003e genera, respectively. Current therapies for these parasitic diseases are often inadequate, plagued by issues such as toxicity, complex administration regimens, and the increasing spread of drug resistance [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Consequently, there is an urgent need for new drug leads with novel mechanisms of action.\u003c/p\u003e \u003cp\u003eNatural products, informed by ethnopharmacological knowledge, represent a vital source for such new chemical entities [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The structural diversity of plant-derived metabolites can help renew the therapeutic arsenal in the continuous fight against resistance. The rich biodiversity of medicinal plants, combined with traditional use, continues to offer promising avenues for drug discovery, as exemplified by the historical success of quinine from \u003cem\u003eCinchona\u003c/em\u003e species and artemisinin from \u003cem\u003eArtemisia annua\u003c/em\u003e [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eGardenia imperialis\u003c/em\u003e K. Schum (Rubiaceae) is a plant used in the traditional Cameroonian pharmacopoeia for the treatment of malaria and related symptoms. The genus \u003cem\u003eGardenia\u003c/em\u003e is known to produce a wide array of biologically active and structurally diverse secondary metabolites [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, this study was undertaken to perform a bioactivity-guided phytochemical investigation of \u003cem\u003eG. imperialis\u003c/em\u003e using chromatographic and spectroscopic techniques, evaluating the extracts and isolated compounds against \u003cem\u003ePlasmodium falciparum\u003c/em\u003e, \u003cem\u003eLeishmania donovani\u003c/em\u003e, and \u003cem\u003eTrypanosoma brucei brucei\u003c/em\u003e.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Plant Material\u003c/h2\u003e \u003cp\u003eLeaves and stem bark of \u003cem\u003eGardenia imperialis\u003c/em\u003e K. Schum were collected in Sangmelima, Cameroon (2.9333\u0026deg; N, 11.9833\u0026deg; E), in August 2021. A voucher specimen (ID 58234/HNC) was deposited at the National Herbarium of Cameroon for identification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Extraction\u003c/h2\u003e \u003cp\u003eThe plant materials were washed, air-dried in the shade, and pulverized. Powdered leaves and stem bark (500 g each) were macerated in 5 L of methanol for 72 h at room temperature. The extracts were filtered, and the filtrates were concentrated under reduced pressure at 50\u0026deg;C using a rotary evaporator. The resulting crude methanolic extracts from the leaves (GIlMeOH) and stem bark (GIsbMeOH) were stored at 4\u0026deg;C for subsequent bioactivity assays.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Bioassay-Guided Fractionation and Isolation\u003c/h2\u003e \u003cp\u003ePreliminary antiparasitic screening identified the leaf extract (GIlMeOH) as the most active. Consequently, 78.6 g of GIlMeOH was subjected to flash chromatography [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] on silica gel (0.063\u0026ndash;0.2 mm) eluted with a stepwise gradient of \u003cem\u003en\u003c/em\u003e-hexane-EtOAc (100:0 to 50:50, v/v), followed by methanol, to yield six major fractions (GI1\u0026ndash;GI6).\u003c/p\u003e \u003cp\u003eFractions GI3, GI5, and GI6, which showed significant antiparasitic activity, were selected for further investigation. These were analyzed by LC\u0026ndash;MS-Q-TOF, and the data were processed using the Global Natural Products Social (GNPS) molecular networking platform for dereplication. The fractions were subsequently purified by Medium/High Pressure Liquid Chromatography (M/HPLC). Fraction GI3 yielded four known flavonoids, while GI5 afforded one flavonoid. The structures of all isolated compounds were elucidated by extensive \u003csup\u003e1\u003c/sup\u003e\u003cem\u003eH\u003c/em\u003e and \u003csup\u003e13\u003c/sup\u003e\u003cem\u003eC\u003c/em\u003e NMR spectroscopy (Supplementary Information 1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Antiparasitic Assays\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 Parasite Cultures\u003c/h2\u003e \u003cp\u003e \u003cem\u003ePlasmodium falciparum\u003c/em\u003e strains 3D7 (chloroquine-sensitive) and Dd2 (multidrug-resistant) were maintained in human O\u0026thinsp;+\u0026thinsp;erythrocytes at 4% hematocrit in complete RPMI 1640 medium (supplemented with 0.5% Albumax II, 25 mM HEPES, and 0.04% gentamicin) at 37\u0026deg;C under a 5% CO₂ atmosphere [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eLeishmania donovani\u003c/em\u003e (strain 1S) promastigotes were cultured at 28\u0026deg;C in M199 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 1% penicillin/streptomycin.\u003c/p\u003e \u003cp\u003e \u003cem\u003eTrypanosoma brucei brucei\u003c/em\u003e (bloodstream form, strain Lister 427) was cultivated at 37\u0026deg;C under 5% CO₂ in HMI-9 medium supplemented with 10% FBS.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Sample Preparation\u003c/h2\u003e \u003cp\u003eStock solutions of extracts, fractions, and isolated compounds (100 mg/mL) and reference drugs were prepared in DMSO. Working concentrations were prepared by serial dilution in the respective culture media, ensuring the final DMSO concentration did not exceed 0.1%.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.4.3 Antiplasmodial Assay\u003c/h2\u003e \u003cp\u003eAnti-\u003cem\u003ePlasmodium\u003c/em\u003e activity was evaluated against synchronized ring-stage cultures [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] of \u003cem\u003eP. falciparum\u003c/em\u003e (3D7 and Dd2) using the SYBR Green I fluorescence method [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Parasites (1% parasitemia, 2% hematocrit) were incubated with test samples for 72 h. Artemisinin and chloroquine (10 \u0026micro;M) served as positive controls, while 0.1% DMSO was the negative control. After lysis with SYBR Green I buffer, fluorescence was measured (excitation/emission: 485/530 nm). The half-maximal inhibitory concentration (IC₅₀) was determined from dose-response curves.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.4.4 Antileishmanial and Antitrypanosomal Assays\u003c/h2\u003e \u003cp\u003eActivity against \u003cem\u003eL. donovani\u003c/em\u003e promastigotes and \u003cem\u003eT. b. brucei\u003c/em\u003e trypomastigotes was assessed using a resazurin-based assay [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Parasites were incubated with test samples for 24 h (\u003cem\u003eL. donovani\u003c/em\u003e) or 68 h (\u003cem\u003eT. b. brucei\u003c/em\u003e), after which resazurin solution was added. Following further incubation, fluorescence was measured (excitation/emission: 530/590 nm). Amphotericin B and pentamidine were used as positive controls for \u003cem\u003eLeishmania\u003c/em\u003e and \u003cem\u003eTrypanosoma\u003c/em\u003e, respectively.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Cytotoxicity Assay\u003c/h2\u003e \u003cp\u003eCytotoxicity against mammalian Vero (ATCC\u0026reg; CRL-1586) and Raw264.7 (ATCC\u0026reg; TIB-71) cell lines was determined using a resazurin assay [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Cells were seeded at 1 \u0026times; 10⁴ cells/well, allowed to adhere, and then treated with samples for 48 h. Resazurin was added, and after 4 h, fluorescence was measured. The half-maximal cytotoxic concentration (CC₅₀) was calculated. The selectivity index (SI) was defined as SI\u0026thinsp;=\u0026thinsp;CC₅₀ (mammalian cells) / IC₅₀ (parasites).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Data Analysis\u003c/h2\u003e \u003cp\u003eAll experiments were performed in duplicate and independently repeated twice. Dose-response curves were plotted using GraphPad Prism 8.0, and IC₅₀/CC₅₀ values were derived by nonlinear regression. Data processing was performed using Microsoft Excel.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Bioassay-Guided Fractionation and Identification of Compounds\u003c/h2\u003e \u003cp\u003eInitial screening of the methanolic extracts from \u003cem\u003eGardenia imperialis\u003c/em\u003e revealed that the leaf extract (GIlMeOH) exhibited potent and broad-spectrum antiparasitic activity with IC\u003csub\u003e50\u003c/sub\u003e values ranging from 5.5 to 10.7 \u0026micro;g/mL and good selectivity (SI\u0026thinsp;\u0026gt;\u0026thinsp;9) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). It was consequently selected for bioassay-guided fractionation.\u003c/p\u003e \u003cp\u003eFractionation of GIlMeOH by flash chromatography yielded several fractions, of which GI3, GI5, and GI6 showed significant activity. The GI3 fraction (eluted with \u003cem\u003en\u003c/em\u003e-hexane-EtOAc, 80:20) was particularly active against \u003cem\u003eP. falciparum\u003c/em\u003e Dd2 (IC₅₀ = 6.9 \u0026micro;g/mL) and \u003cem\u003eT. b. brucei\u003c/em\u003e (IC₅₀ = 4.8 \u0026micro;g/mL) and was therefore subjected to further purification.\u003c/p\u003e \u003cp\u003eSubsequent HPLC separation and spectroscopic analysis of fraction GI3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) led to the isolation and identification of four flavonoids (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026amp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The structures of these compounds were established as hispidulin (\u003cb\u003e1\u003c/b\u003e), 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone (\u003cb\u003e2\u003c/b\u003e), gradenin A (\u003cb\u003e3\u003c/b\u003e), and salvigenin (\u003cb\u003e4\u003c/b\u003e) based on \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR and MS data (Supplementary Information). The \u003csup\u003e1\u003c/sup\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:H\\)\u003c/span\u003e\u003c/span\u003e and \u003csup\u003e13\u003c/sup\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:C\\)\u003c/span\u003e\u003c/span\u003e NMR data for these compounds are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026amp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Compound 5,7,3\u0026rsquo;,trihydroxy-6-4\u0026rsquo;5\u0026rsquo;-trimethoxyflavone along with 6 subfractions (GI3.2f, GI3.2 g, GI3.2 h, GI3.2i, GI3.3a, and GI3.3g) exhibited a broad-spectrum antiparasitic activity with IC\u003csub\u003e50\u003c/sub\u003e values ranging from 0.6 \u0026micro;g/mL to 23.9 \u0026micro;g/mL and good selectivity. Salvogenin, gradenin A, and hispidulin potently inhibited \u003cem\u003eT. b. brucei\u003c/em\u003e with IC\u003csub\u003e50\u003c/sub\u003e values of 2.5 \u0026micro;g/mL, 2.8 \u0026micro;g/mL, and 15.6 \u0026micro;g/mL, respectively. Fractionation of fraction GI5 led to one inactive flavonoid, cirsimaritin (\u003cb\u003e5\u003c/b\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003csup\u003e1\u003c/sup\u003e\u003cem\u003eH\u003c/em\u003e NMR data for compounds (1\u0026ndash;5) compared with literature data.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispidulin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFlavone\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGradenin A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSavigenin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCirsimaritin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e12.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e12.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e7.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e7.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e7.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e7.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e6.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e6.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e6.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e6.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e3.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e3.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003csup\u003e13\u003c/sup\u003e\u003cem\u003eC\u003c/em\u003e NMR data for compounds (1\u0026ndash;5) compared with literature data.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispidulin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFlavone\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGradenin A\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSalvigenin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCirsimaritin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e182.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e182.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e182.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e182.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e182.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e182.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e182.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e182.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e182.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e182.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e163.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e163.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e165.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e163.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e163.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e163.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e163.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e164.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e163.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e163.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e161.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e161.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e153.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e153.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e158.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e158.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e162.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e162.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e161.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e161.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e157.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e157.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e152.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e152.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e153.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e153.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e158.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e158.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e158.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e158.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e152.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e152.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e150.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e150.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e153.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e153.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e152.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e153.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e152.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e152.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e152.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e152.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e139.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e139.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e153.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e153.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e127.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e128.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e152.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e152.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e131.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e125.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e125.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e141.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e141.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e123.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e123.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e131.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e131.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e121.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e107.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e107.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e132.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e132.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e114.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e114.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e128.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e128.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e103.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e104.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e104.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e126.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e126.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e121.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e121.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e128.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e128.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e102.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e102.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e106.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e106.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e90.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e90.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e115.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e115.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e115.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e105.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e105.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e60.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e60.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e104.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e94.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e94.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e59.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e103.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e103.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e56.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e56.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e102.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e102.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e102.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e90.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e90.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e55.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e55.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e94.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e94.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e59.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e157.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e157.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e61.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e61.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e59.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e59.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e152.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e152.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e60.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e56.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e56.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e56.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e56.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Experimental Section\u003c/h2\u003e \u003cp\u003e \u003cem\u003eHispidulin\u003c/em\u003e (\u003cb\u003e1\u003c/b\u003e): Yellow compound. \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra (DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sub\u003e), see Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; (+)-HRESIMS: \u003cem\u003em/z\u003c/em\u003e [M\u0026thinsp;+\u0026thinsp;H] \u003csup\u003e+\u003c/sup\u003e calc. for C\u003csub\u003e16\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e 301.0700 (calcd for C\u003csub\u003e16\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6,\u003c/sub\u003e 301.0634; Δ3.47ppm) calc. [M\u0026thinsp;+\u0026thinsp;Na] 323.0516,\u003c/p\u003e \u003cp\u003e \u003cem\u003e5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone\u003c/em\u003e (\u003cb\u003e2\u003c/b\u003e): Yellow powder, \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra (DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sub\u003e), see Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; (+)-HRESIMS: \u003cem\u003em/z\u003c/em\u003e [M\u0026thinsp;+\u0026thinsp;H] \u003csup\u003e+\u003c/sup\u003e calc. for C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003e 361.0895 (calcd for C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e8,\u003c/sub\u003e 361.0923; Δ1.36ppm), calc. [M\u0026thinsp;+\u0026thinsp;Na] 383.0703.\u003c/p\u003e \u003cp\u003e \u003cem\u003eGradenin A\u003c/em\u003e (\u003cb\u003e3\u003c/b\u003e): White powder, \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra (DMSO-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e\u003cem\u003e6\u003c/em\u003e\u003c/sub\u003e), see Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; (+)-HRESIMS: \u003cem\u003em/z\u003c/em\u003e [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e calc. for C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e20\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003e 389.1215 (calcd for C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e20\u003c/sub\u003eO\u003csub\u003e8,\u003c/sub\u003e 389.1236; Δ2.40ppm), calc. [M\u0026thinsp;+\u0026thinsp;Na] 411.1034.\u003c/p\u003e \u003cp\u003e \u003cem\u003eSalvigenin\u003c/em\u003e (\u003cb\u003e4\u003c/b\u003e): White powder, \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra (CDCl\u003csub\u003e3\u003c/sub\u003e), see Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; (+)-HRESIMS: \u003cem\u003em/z\u003c/em\u003e [M\u0026thinsp;+\u0026thinsp;H] \u003csup\u003e+\u003c/sup\u003e calc. for C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e 329.1028 (calcd for C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e6,\u003c/sub\u003e 329.1025; Δ0.91ppm), calc. [M\u0026thinsp;+\u0026thinsp;Na] 351.0849.\u003c/p\u003e \u003cp\u003e \u003cem\u003eCirsimaritin\u003c/em\u003e (\u003cb\u003e5\u003c/b\u003e): White powder, \u003csup\u003e1\u003c/sup\u003eH and \u003csup\u003e13\u003c/sup\u003eC NMR spectra (CDCl\u003csub\u003e3\u003c/sub\u003e), see Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; (+)-HRESIMS: \u003cem\u003em/z\u003c/em\u003e [M\u0026thinsp;+\u0026thinsp;H] \u003csup\u003e+\u003c/sup\u003e calc. for C\u003csub\u003e17\u003c/sub\u003eH\u003csub\u003e14\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e 315.0872 (calcd for C\u003csub\u003e17\u003c/sub\u003eH\u003csub\u003e14\u003c/sub\u003eO\u003csub\u003e6,\u003c/sub\u003e 315.0868; Δ1.27ppm), calc. [M\u0026thinsp;+\u0026thinsp;Na] 337.0689.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntiparasitic activity and selectivity of \u003cem\u003eGardenia imperialis\u003c/em\u003e extracts, fractions, and compounds\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCodes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVero/Raw264.7 Cells\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c8\" namest=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP. falciparum IC50 (\u0026micro;g/mL)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c12\" namest=\"c9\"\u003e \u003cp\u003e\u003cem\u003eKinetoplastids IC50 (\u0026micro;g/mL)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrude extracts\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCC50 (\u0026micro;g/mL)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ePf\u003c/em\u003eDd2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eSIVero/Dd2\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ePf\u003c/em\u003e3D7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eSIVero/3D7\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eL. donovani\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eSIRaw264.7\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eT. b. brucei\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cem\u003eSIVero\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGIsbMeOH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGIlMeOH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;18.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e9.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFractions\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGI3:Hex- EtOAc (80:20)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSubfractions/compounds\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2a (Gradenin A)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;35.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2b (Salvigenin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2c (Hispidulin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;6.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2d (5,7,3\u0026rsquo;-Trihydroxy-6-4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e 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\u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e8.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;12.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;35.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e9.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2 g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;66.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2 h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;21.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;76.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e12.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2j\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2k\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;14.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e13.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;7.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.2 l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.3a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;11.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.3b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;18.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.3c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e 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align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;45.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.3 f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;90.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.3 g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;166.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI3.3h\u003c/p\u003e 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align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;17.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI5.4 (Cirsimaritin)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;15.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGI6: Residue (MeOH)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReference drugs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArtemisinin (\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChloroquine (\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmphotericin B (\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePentamidine (\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.006\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePodophyllotoxin (\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIC\u003csub\u003e50\u003c/sub\u003e: 50% inhibitory concentration; CC\u003csub\u003e50\u003c/sub\u003e: 50% cytotoxic concentration; Activity values were derived for sigmoidal dose-response curves fitted by non-linear regression using GraphPad Prism 8.0 software; SD: standard deviation; Plant samples were tested in triplicate experiments against parasites in normal culture conditions; GIsbMeOH: Methanolic extract from stem bark of \u003cem\u003eG. imperialis\u003c/em\u003e; GIlMeOH: Methanolic extract from leaves of \u003cem\u003eG. imperialis\u003c/em\u003e; RI: Resistance index\u0026thinsp;=\u0026thinsp;IC\u003csub\u003e50\u003c/sub\u003e\u003cem\u003ePf\u003c/em\u003eDd2/IC\u003csub\u003e50\u003c/sub\u003e\u003cem\u003ePf\u003c/em\u003e3D7; SIVero: Selectivity index when tested on Vero cells; SIRaw264.7: Selectivity index when tested on Raw264.7 cells.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study provides the first comprehensive report on the antiparasitic properties of \u003cem\u003eGardenia imperialis\u003c/em\u003e. While the fractionation process successfully concentrated the antitrypanosomal activity, it did not significantly enhance the potency against \u003cem\u003ePlasmodium\u003c/em\u003e or \u003cem\u003eLeishmania\u003c/em\u003e compared to the crude leaf extract (GIlMeOH). A key finding was that all active samples, including the crude extract, fractions, and isolated compounds, demonstrated an antiplasmodial resistance index (RI) of less than 1. This indicates a consistent and promising preferential inhibition of the multidrug-resistant \u003cem\u003eP. falciparum\u003c/em\u003e Dd2 strain over the sensitive 3D7 strain.\u003c/p\u003e \u003cp\u003eThe observed antiplasmodial activity aligns with previous studies on other \u003cem\u003eGardenia\u003c/em\u003e species. Extracts from \u003cem\u003eG. sokotensis\u003c/em\u003e, \u003cem\u003eG. lutea\u003c/em\u003e, \u003cem\u003eG. ternifolia\u003c/em\u003e, and \u003cem\u003eG. saxatilis\u003c/em\u003e have all shown activity against various \u003cem\u003ePlasmodium\u003c/em\u003e strains [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], supporting the genus as a source of anti-malarial compounds. Previous phytochemical investigations of these species have identified flavonoids and triterpenoids [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], compound classes consistent with our findings.\u003c/p\u003e \u003cp\u003eOur bioassay-guided approach led to the isolation of several flavonoids. Among them, hispidulin confirmed its known broad-spectrum antiprotozoal potential, showing activity against all three parasites tested [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The most significant contributions of this work, however, are the first reports of antiparasitic activity for three compounds: gradenin A, salvigenin, and 5,7,3\u0026rsquo;-trihydroxy-6,4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone.\u003c/p\u003e \u003cp\u003eNotably, gradenin A and salvigenin exhibited potent antitrypanosomal activity (IC₅₀ = 2.8 and 2.5 \u0026micro;g/mL, respectively). While salvigenin is known for its anti-inflammatory, analgesic, and anticancer properties [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], its activity against \u003cem\u003eT. b. brucei\u003c/em\u003e is described here for the first time. In contrast, gradenin A appears to be a largely unexplored natural product. It is listed in the ChEMBL database (CHEMBL485823) but, to the best of our knowledge, no biological activity has been previously reported. Its potent antitrypanosomal activity identified in this study positions it as a promising novel scaffold for future investigation.\u003c/p\u003e \u003cp\u003eSimilarly, the broad-spectrum antiparasitic activity of 5,7,3\u0026rsquo;-trihydroxy-6,4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone against \u003cem\u003eP. falciparum\u003c/em\u003e, \u003cem\u003eL. donovani\u003c/em\u003e, and \u003cem\u003eT. b. brucei\u003c/em\u003e is reported here for the first time. Its structural similarity to other bioactive trimethoxyflavones [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] suggests a potential mechanism of action worthy of further exploration.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis bioactivity-guided investigation of \u003cem\u003eGardenia imperialis\u003c/em\u003e validates its traditional use and identifies its leaves as a source of potent antiparasitic compounds. The study successfully isolated several flavonoids, with the antitrypanosomal activities of gradenin A and salvigenin being particularly notable. Furthermore, the broad-spectrum activity of 5,7,3\u0026rsquo;-trihydroxy-6,4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone against \u003cem\u003ePlasmodium falciparum\u003c/em\u003e, \u003cem\u003eLeishmania donovani\u003c/em\u003e, and \u003cem\u003eTrypanosoma brucei brucei\u003c/em\u003e is reported here for the first time. The consistent preference for inhibiting the multidrug-resistant \u003cem\u003eP. falciparum\u003c/em\u003e Dd2 strain is another promising finding. These results warrant further investigation into these natural products as novel and selective lead compounds for the development of new treatments for malaria and neglected tropical diseases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eACT\u003c/strong\u003e: Artemisinin-based Combination Therapy; \u003cstrong\u003eATCC\u003c/strong\u003e: American Type Culture Collection; \u003cstrong\u003eBEI\u003c/strong\u003e \u003cstrong\u003eResources\u003c/strong\u003e: Biodefense and Emerging Infections Research Resources Repository; \u003cstrong\u003eCC\u003csub\u003e50\u003c/sub\u003e\u003c/strong\u003e : 50% Cytotoxic Concentration; \u003cstrong\u003eDMEM\u003c/strong\u003e: Dulbecco\u0026rsquo;s Modified Eagle\u0026rsquo;s Medium; \u003cstrong\u003eDMSO\u003c/strong\u003e: DiMethylSulfOxyde; \u003cstrong\u003eEDTA\u003c/strong\u003e: Tetracyclic Ethylene Diamine; \u003cstrong\u003eFBS\u003c/strong\u003e: F\u0026oelig;tal Bovin Serum; \u003cstrong\u003eHEPES\u003c/strong\u003e: 4-(2-hydroxyethyl) -1-piperazineethanesulfonic acid; \u003cstrong\u003eHex\u003c/strong\u003e: hexane; \u003cstrong\u003eIC\u003csub\u003e50\u003c/sub\u003e\u003c/strong\u003e : 50% Inhibitory Concentration; \u003cstrong\u003eMeOH\u003c/strong\u003e: Methanol; \u003cstrong\u003eNMR\u003c/strong\u003e: Nuclear Magnetic Resonance Spectrometer; \u003cstrong\u003e\u003cem\u003eP. falciparum\u003c/em\u003e\u003c/strong\u003e:\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003ePlasmodium falciparum ; \u0026nbsp;\u003cstrong\u003ePf\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e3D7\u003c/strong\u003e: \u003cem\u003ePlasmodium falciparum\u0026nbsp;\u003c/em\u003e3D7 \u003cstrong\u003e\u003cem\u003ePf\u003c/em\u003eDd2\u003c/strong\u003e : \u003cem\u003ePlasmodium falciparum\u003c/em\u003e Dd2; \u003cstrong\u003eRPMI 1640\u003c/strong\u003e: Roswell Park Memorial Institute 1640; \u003cstrong\u003eSD\u003c/strong\u003e: Standard Deviation; \u003cstrong\u003eSI\u003c/strong\u003e: Selectivity index (CC\u003csub\u003e50\u003c/sub\u003e/IC\u003csub\u003e50\u003c/sub\u003e); \u003cstrong\u003e\u003cem\u003eSIRaw264.7\u003c/em\u003e\u003c/strong\u003e: Selective Index for Raw264.7 cells;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eSIVero\u003c/em\u003e\u003c/strong\u003e: Selective Index for \u0026nbsp;Vero cells; GIsbMeOH: Methanolic extract from stem bark of \u003cem\u003eG. imperialis\u003c/em\u003e; GIlMeOH: Methanolic extract from leaves of \u003cem\u003eG. imperialis\u003c/em\u003e; RI: Resistance index = IC\u003csub\u003e50\u003c/sub\u003e\u003cem\u003ePf\u003c/em\u003eDd2/IC\u003csub\u003e50\u003c/sub\u003e\u003cem\u003ePf\u003c/em\u003e3D7.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article and its supplementary information file.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding and/or Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not receive support from any organization for the submitted work. \u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no competing interests to declare that are relevant to the content of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChristelle Wayoue Kom: Investigation, Methodology, Software, Visualization, Validation, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eSylvester Osei Bobbie: Investigation, Methodology, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eDarline Dize: Investigation, Methodology, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eMariscal Brice Tchatat Tali: Investigation, Methodology, Validation, review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eCyrille A.N. Ngansop: \u0026nbsp;Investigation, Methodology, Software;\u003c/p\u003e\n\u003cp\u003eLauve R.T. Yamthe: \u0026nbsp;Methodology, Writing \u0026ndash; review \u0026amp; editing;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBill Baker: \u0026nbsp;Validation, Supervision, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eFabrice Fekam Boyom: Conceptualization, Funding acquisition, Validation, Supervision, Writing \u0026ndash; review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eAll the authors approved the final version of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their gratitude to BEI Resources (https://www.beiresources.org/) for providing the parasitic strains and to the Department of Chemistry at the University of South Florida, Tampa, USA, for their assistance with compound identification. They also acknowledge the valuable contribution of the Cameroon National Herbarium, Yaounde, for plant identification.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePriya V. WHO world malaria report 2024. \u003cem\u003eLancet Microbe\u003c/em\u003e. 2024;6(4):101073.\u003c/li\u003e\n\u003cli\u003eRoy S, Chancey R, Cantey P, Straily A. Trypanosomiasis, African. \u003cem\u003eCDC Yellow Book\u003c/em\u003e. 2024. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2024/infectious-diseases/trypanosomiasis-african.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Leishmaniasis. 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis.\u003c/li\u003e\n\u003cli\u003eMaloueki U, Mbomba ID, Ndimbo KSP. Screening phytochimique et activit\u0026eacute;s antiplasmodiales compar\u0026eacute;es de quelques plantes consomm\u0026eacute;es par les bonobos (Pan paniscus) de la station de Lui-Kotale, R.D. Congo. \u003cem\u003eAnn Afr Med\u003c/em\u003e. 2015;6:64.\u003c/li\u003e\n\u003cli\u003eDize D, Tali MBT, Ngansop CAN, Keumoe R, Madiesse Kemgne EA, Yamthe LRT, Tsouh Fokou PV, Pone Kamdem B, Hata K, Fekam Boyom F. Target-based 6\u0026ndash;5 fused ring heterocyclic scaffolds display broad antiparasitic potency in vitro. \u003cem\u003eFuture Pharmacol\u003c/em\u003e. 2024;4(1):188\u0026ndash;198. https://doi.org/10.3390/futurepharmacol4010013.\u003c/li\u003e\n\u003cli\u003eOrtiz JE, Pi\u0026ntilde;eiro M, Kaiser M, M\u0026auml;ser P, Bastida J, Feresin GE. Anti-trypanosomatid and antiplasmodial activities of alkaloids from \u003cem\u003eHippeastrum\u003c/em\u003e species. \u003cem\u003eChem Biodivers\u003c/em\u003e. 2025;22(8):e202500015. doi:10.1002/cbdv.202500015.\u003c/li\u003e\n\u003cli\u003eBoyom FF, Tsouh FVP, Tchokouaha YRL, Mfopa NA, Kemgne ME, Mbacham FW, Tsamo ET, Zollo APH, Gut J, Rosenthal PJ. Potent antiplasmodial extracts from Cameroonian Annonaceae. \u003cem\u003eJ Ethnopharmacol\u003c/em\u003e. 2011;134:717\u0026ndash;724.\u003c/li\u003e\n\u003cli\u003eMao EY, Page SW, Sleebs BE, Gancheva MR, Wilson DW. A review of natural products as a source of next-generation drugs against apicomplexan parasites. \u003cem\u003eNPJ Antimicrob Resist\u003c/em\u003e. 2025;3(1):51. doi:10.1038/s44259-025-00119-x.\u003c/li\u003e\n\u003cli\u003eAgbodjento E, Kloto\u0026eacute; JR, Dramane G, Dougnon TV, Ategbo JM. \u003cem\u003eGardenia ternifolia\u003c/em\u003e Schumach. \u0026amp; Thonn.: revue sur les aspects ethnobotanique, ethnopharmacologique, phytochimique et toxicologique. \u003cem\u003eInt J Biol Chem Sci\u003c/em\u003e. 2018;12(6):2922\u0026ndash;2932.\u003c/li\u003e\n\u003cli\u003eOkoye TC, Akah PA, Ezike AC, Okoye MO, Onyeto CA, Ndukwu F. Evaluation of the acute and subacute toxicity of \u003cem\u003eAnnona senegalensis\u003c/em\u003e root bark extracts. \u003cem\u003eAsian Pac J Trop Med\u003c/em\u003e. 2012;5(4):277\u0026ndash;282.\u003c/li\u003e\n\u003cli\u003eLambros C, Vanderberg JP. Synchronization of \u003cem\u003ePlasmodium falciparum\u003c/em\u003e erythrocytic stages in culture. \u003cem\u003eJ Parasitol\u003c/em\u003e. 1979;65:418\u0026ndash;420.\u003c/li\u003e\n\u003cli\u003eSmilkstein M, Sriwilaijaroen N, Kelly JX, Wilairat P, Riscoe M. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. \u003cem\u003eAntimicrob Agents Chemother\u003c/em\u003e. 2004;48:1803\u0026ndash;1806. https://doi.org/10.1128/AAC.48.5.1803.\u003c/li\u003e\n\u003cli\u003eSiqueira-Neto JL, Song OR, Oh H, Sohn JH, Yang G, et al. Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds. \u003cem\u003ePLoS Negl Trop Dis\u003c/em\u003e. 2010;4(5):e675. doi:10.1371/journal.pntd.0000675.\u003c/li\u003e\n\u003cli\u003eBowling T, Mercer L, Don R, Jacobs R, Nare B. Application of a resazurin-based high-throughput screening assay for the identification and progression of new treatments for human African trypanosomiasis. \u003cem\u003eInt J Parasitol Drugs Drug Resist\u003c/em\u003e. 2012;2:262\u0026ndash;270.\u003c/li\u003e\n\u003cli\u003eJansen O, Angenot L, Tits M, Nicolas JP, De Mol P, Nikiema JB, Frederich M. Evaluation of 13 selected medicinal plants from Burkina Faso for their antiplasmodial properties. \u003cem\u003eJ Ethnopharmacol\u003c/em\u003e. 2010;130(1):143\u0026ndash;150.\u003c/li\u003e\n\u003cli\u003eEl Tahir A, Satti GMH, Khalid SA. Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on \u003cem\u003eMaytenus senegalensis\u003c/em\u003e (Lam.) Exell. \u003cem\u003eJ Ethnopharmacol\u003c/em\u003e. 1999;64:227\u0026ndash;233.\u003c/li\u003e\n\u003cli\u003eSuksamrarn A, Tanachatchairatana T, Kanokmedhakul S. Antiplasmodial triterpenes from twigs of \u003cem\u003eGardenia saxatilis\u003c/em\u003e. \u003cem\u003eJ Ethnopharmacol\u003c/em\u003e. 2003;88:275\u0026ndash;277.\u003c/li\u003e\n\u003cli\u003eS\u0026uuml;lsen VP, Cazorla SI, Frank FM, Redko FC, Anesini CA, Coussio JD, Malchiodi EL, Martino VS, Mischietti LV. Trypanocidal and leishmanicidal activities of flavonoids from Argentine medicinal plants. \u003cem\u003eAm J Trop Med Hyg\u003c/em\u003e. 2007;77:654\u0026ndash;659.\u003c/li\u003e\n\u003cli\u003eGrecco Sdos S, Felix MJ, Lago JH, Pinto GE, Tempone AG, Romoff P, Ferreira JMP, Sartorelli P. Anti-trypanosomal phenolic derivatives from \u003cem\u003eBaccharis uncinella\u003c/em\u003e. \u003cem\u003eNat Prod Commun\u003c/em\u003e. 2014;9:171\u0026ndash;173.\u003c/li\u003e\n\u003cli\u003eMansourabadi AM, Sadeghi HM, Razavi N, Rezvani E. Anti-inflammatory and analgesic properties of salvigenin, a \u003cem\u003eSalvia officinalis\u003c/em\u003e flavonoid extract. \u003cem\u003eAdv Herbal Med\u003c/em\u003e. 2015;1:31\u0026ndash;41.\u003c/li\u003e\n\u003cli\u003eMansourizadeh F, Houri Sepehri, Khoee S, Farimani MM, Delphi L, Tousi MS. Designing salvigenin-loaded mPEG-b-PLGA@Fe₃O₄ nanoparticles for enhanced anti-cancer effects on breast cancer cells: an in vitro study. \u003cem\u003eJ Drug Deliv Sci Technol\u003c/em\u003e. 2020;57:101619. https://doi.org/10.1016/j.jddst.2020.101619.\u003c/li\u003e\n\u003cli\u003eTang J, Wang W, Luan F, Chen X. Binding of the bioactive compound 5,7,4\u0026prime;-trihydroxy-6,3\u0026prime;,5\u0026prime;-trimethoxyflavone to human serum albumin. \u003cem\u003eInt J Biol Macromol\u003c/em\u003e. 2005;37(1\u0026ndash;2):85\u0026ndash;91. doi:10.1016/j.ijbiomac.2005.08.010.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Yaounde 1","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Gardenia imperialis, Antiparasitic activity, Plasmodium falciparum, Leishmania donovani, Trypanosoma brucei brucei, Natural roducts","lastPublishedDoi":"10.21203/rs.3.rs-8460808/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8460808/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e \u003cem\u003eGardenia imperialis\u003c/em\u003e is used in Cameroonian traditional medicine to treat malaria and related symptoms. This study aimed to conduct a phytochemical investigation of \u003cem\u003eG. imperialis\u003c/em\u003e extracts through bioassay-guided fractionation to identify anti-parasitic compounds.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eCrude methanolic extracts from the leaves and stem bark were subjected to bioassay-guided fractionation using liquid chromatography\u0026ndash;mass spectrometry (LC\u0026ndash;MS) and preparative high-performance liquid chromatography (HPLC). The structures of isolated natural products were elucidated by spectroscopic analysis, including NMR and MS. All extracts, fractions, subfractions, and pure compounds were evaluated for cytotoxicity against Vero and Raw264.7 cell lines and for anti-parasitic activity against \u003cem\u003ePlasmodium falciparum\u003c/em\u003e (Dd2 and 3D7 strains), \u003cem\u003eTrypanosoma brucei brucei\u003c/em\u003e, and \u003cem\u003eLeishmania donovani\u003c/em\u003e.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe leaf methanolic extract (GIlMeOH) exhibited broad-spectrum anti-parasitic activity (IC₅₀ \u0026lt; 11 \u0026micro;g/mL) without cytotoxicity towards mammalian cell lines. Dereplication and isolation yielded fractions, subfractions, and compounds with improved activity (IC₅₀ values ranging from 0.67 to 37.2 \u0026micro;g/mL). Among the isolated compounds, gradenin A, salvigenin, hispidulin, and 5,7,3\u0026rsquo;-trihydroxy-6,4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone showed potent antitrypanosomal activity with IC₅₀ values of 2.8, 2.5, 16.6, and 9.7 \u0026micro;g/mL, respectively. The anti-parasitic activities of gradenin A, salvigenin, and 5,7,3\u0026rsquo;-trihydroxy-6,4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone are reported here for the first time.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe promising anti-parasitic profile of the \u003cem\u003eG. imperialis\u003c/em\u003e leaf extract and its isolated constituents, particularly and 5,7,3\u0026rsquo;-trihydroxy-6,4\u0026rsquo;,5\u0026rsquo;-trimethoxyflavone, gradenin A, and salvigenin, supports further investigation into their potential as novel and selective agents against parasitic diseases.\u003c/p\u003e","manuscriptTitle":"Integrating Biology and Phytochemistry to Identify Antiparasitic Natural Products from Gardenia imperialis K. Schum (Rubiaceae)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-07 14:43:41","doi":"10.21203/rs.3.rs-8460808/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f9e41669-e025-4148-bef9-e1289cf20f97","owner":[],"postedDate":"January 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60270586,"name":"Parasitology"}],"tags":[],"updatedAt":"2026-01-07T14:43:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-07 14:43:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8460808","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8460808","identity":"rs-8460808","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}