Polygonatum odoratum (Mill.) Druce: A Review of Traditional Uses, Phytochemistry, Mass Spectrometric Fragmentation, Pharmacology, Toxicology, and Q-Marker Prediction.

Polygonatum odoratum (Mill.) Druce (Angular Solomon’s seal), known as “Yuzhu” in Chinese, is an ornamental plant and herbal drug belonging to the genus Polygonatum (Solomon’s seal) in the family Asparagaceae. Morphologically, the plant features a single stem, often inclined to one side, with a smooth hairless surface with ridges. The leaves were somewhat leathery and elliptical in shape. The rhizome bears waxy scars left after the old stems die back, which resemble ancient royal seals–hence the English common name “Angular Solomon’s seal”. This feature can also serve as a basis for morphological identification. P. odoratum typically grows in mountainous forests, wilderness areas, or rock crevices, preferring shady and moist environments. It is usually harvested in the spring and autumn. The plant morphology is shown in Figure 1 . This species is widely distributed in China in various provinces and regions, including Shandong, Jilin, Shanxi, Ningxia, Hubei, Hunan, Sichuan, Zhejiang, and Anhui. It is included in the list of genuine regional medicinal materials in Shandong Province. 1 Figure 1 ( A ) Flowers, ( B ) rhizomes, ( C ) rhizome slices of Polygonatum odoratum (Mill.) Druce and ( D ) books arranged in chronological order. (( A and B ) are cited from iplant: https://www.iplant.cn ). The image A shows Polygonatum odoratum plant with leaves and flowers. The image B shows the rhizomes of the plant. The image C shows slices of the rhizome. The image D presents a timeline of historical uses of Polygonatum odoratum in traditional medicine. It includes: ′Shen Nong Ben Cao Jing′ from Eastern Han for relieving wasting-thirst, ′Rihuazi Bencao′ from Five Dynasties for alleviating vexation and quenching thirst, ′Bencao Shiyi′ from Tang Dynasty to enhance intelligence and regulate qi and blood, ′Bencao Gangmu′ from Ming Dynasty to treat consumptive diseases with alternating chills and fever, ′Bencao Xinbian′ from Qing Dynasty to nourish yin, moisten the lungs and tonify the stomach and ′Bencao Zhengyi′ from Qing Dynasty to improve lung-stomach dryness-heat. Images of Polygonatum odoratum plant, rhizomes, slices and historical uses timeline. ( A ) Flowers, ( B ) rhizomes, ( C ) rhizome slices of Polygonatum odoratum (Mill.) Druce and ( D ) books arranged in chronological order. (( A and B ) are cited from iplant: https://www.iplant.cn ). P. odoratum is a yin-nourishing medicinal herb that provides tonic effects without causing greasiness and has a history of use as both a medicine and food source. The “medicine and food homology” concept, a fundamental principle in traditional Chinese medicine (TCM), has garnered increasing attention in research focused on its applications in the food and nutraceutical sectors. Its medicinal use was first documented under the name “Wei Rui” in Shen Nong Ben Cao Jing , where it was classified as a superior grade herb. 2 P. odoratum has a sweet, neutral taste. It is slightly cold and nontoxic, and acts on the lung and stomach meridians. It nourishes yin, moistens the lungs, benefits the stomach, and promotes fluid production. It is used to treat conditions, such as dryness, heat, yin impairment, heat damage, and stomach yin deficiency. P. odoratum enhances immunity, strengthens the heart, lowers blood sugar, and reduces blood lipids, and has a history of thousands of years as a treatment for diseases in China. 3 Phytochemical investigations have revealed that P. odoratum is abundant in bioactive constituents, with steroidal saponins, homoisoflavonoids, and polysaccharides being the most representative. 4–8 Accumulating evidence has demonstrated that both crude extracts and isolated compounds from this plant exhibit promising hypoglycemic, immunomodulatory, antioxidant, anti-inflammatory, and antitumor activities. 9–12 These findings provide a reference for the traditional applications of P. odoratum and suggest its promising prospects in new drug development. Although the pharmacological activities of P. odoratum have attracted extensive interest, its complete medicinal profile remains unclear. A systematic review integrating traditional uses, phytochemistry, fragmentation behavior, pharmacology, safety assessment, and Q-marker prediction is still unavailable. Through a comprehensive synthesis of these dimensions, this review seeks to address this deficiency and offer theoretical support for the rational utilization and improved quality control of P. odoratum .

Based on the established fragmentation behavior observed in both the positive- and negative-ion modes, steroidal saponins can be categorized into six distinct aglycone core types based on reference standards, as illustrated in Figure 7A . The core type was primarily identified using the fragment ion information obtained in the positive-ion mode. Key diagnostic fragment ions included m/z 429, 415, 413, and 411. The detection of m/z 413 was an initial indicator that the compound was type I or type III. The presence of m/z 411 suggests potential structures corresponding to type II compounds, and that of m/z 415 and 429 may preliminarily point to type IV and V compounds, respectively. In the negative-ion mode, compounds bearing sugar moieties at both C-3 and C-26 were preferentially cleaved at the C-3 glycosidic bond. When combined with the summarized fragmentation rules, this analytical framework can be effectively applied to identify unknown constituents in samples. 21 Figure 7 ( A ) Core types of steroidal saponins and fragmentation pathways of ( B ) polygodoraside G ( 21 ), ( C ) polygodoraside F ( 33 ), ( D ) typaspidoside H ( 37 ). B 1 : β -D-Glucopyranosyl. Image A depicts six 2D skeletal steroid-like fused ring cores labeled I-VI, with substituents R1 and R2 and OH groups. Stereochemistry is shown with wedge and dashed bonds. One core has an oxygen atom in a five-membered ring. A red sugar-like substituent, B1, is at the lower right with OH labels. Image B presents a grid of 2D skeletal steroidal saponin structures connected by arrows for stepwise fragmentation. Each structure has the same fused ring core and sugar chains with O and OH labels. Text near structures shows m/z values for ions. Image C displays fragmentation sequences in rows with arrows between products. The fused ring core repeats with varying sugar chains and OH labels, annotated with m/z numbers. Image D shows additional fragmentation pathways in rows with arrows. The drawings repeat the fused ring core with sugar chains, OH labels and m/z annotations near intermediates and final products. Four 2D skeletal formula panels of steroidal saponin cores I to VI and fragmentation arrows with m over z labels. ( A ) Core types of steroidal saponins and fragmentation pathways of ( B ) polygodoraside G ( 21 ), ( C ) polygodoraside F ( 33 ), ( D ) typaspidoside H ( 37 ). B 1 : β -D-Glucopyranosyl. The core structural feature of furostanol saponins is the presence of a Δ5 double bond and C22 hydroxyl group, as exemplified by polygodoraside G ( 21 ). In some compounds, an additional double bond is observed at either Δ20 or Δ22, such as polygodoraside F ( 33 ) and typaspidoside H ( 37 ). A general fragmentation pattern of furostanol saponins involves sequential cleavage of the sugar chain at the C-3 position from the outermost to the innermost residue. Notably, the C-26-linked sugar moiety remained stable during fragmentation in negative-ion mode. In negative-ion mode, fragmentation followed a sequential pattern of deglycosylation followed by dehydration. Polygodoraside G ( 21 ), for example, generated m/z 609 [M-H-Glc-2Glc-Glc] − and m/z 591 [M-H-Glc-2Glc-Glc-H 2 O] − fragments, indicating a pathway involving the loss of all four glycosyl moieties followed by a single dehydration step. Polygodoraside F ( 33 ) and typaspidoside H ( 37 ) were shown to exhibit similar patterns, producing characteristic fragments at m/z 751 [M-H-Xyl-Glc-Glc-H 2 O] − and m/z 573 [M-H-Xyl-Glc-Glc-Gal-H 2 O] − , respectively. In positive-ion mode, there are key differences in the fragmentation pathways. The characteristic glycosyl moiety at the C-26 position may be lost, and the hydroxyl groups at both the C-3 and C-14 positions may participate in the dehydration reactions. This process yielded characteristic aglycone ions at m/z 413 and m/z 411. For example, polygodoraside G ( 21 ) produced m/z 413 [M+H-2Glc-Glc-Gal-H 2 O-Glc] + , 395 [M+H-2Glc-Glc-Gal-H 2 O-Glc-H 2 O] + , and 281 [M+H-2Glc-Glc-Gal-H 2 O-Glc-H 2 O-C 6 H 10 O 2 ] + fragments. Polygodoraside F ( 33 ) produced m/z 411 [M+H-H 2 O-H 2 O-Glc-Xyl-Glc-Gal-Glc] + and m/z 393 [M+H-H 2 O-H 2 O-Glc-Xyl-Glc-Gal-Glc-H 2 O] + fragments. Typaspidoside H ( 37 ) generated m/z 413 [M+H-H 2 O-Glc-Xyl-Glc-Gal-Glc] + and 395 [M+H-H 2 O-Glc-Xyl-Glc-Gal-Glc-H 2 O] + . The fragmentation pathways of compounds 21, 33 , and 37 are shown in Figure 7B–D . For the identification of steroidal saponins based on their established fragmentation pathways, the results for compounds 21, 33 , and 37 were confirmed by the characteristic ions observed in the positive-ion mode ( m/z 413 and 411). Key mass spectrometric features indicated that the core types of compounds 21, 33 , and 37 could be further classified as types I, II, and III, respectively ( Figure 7B–D ). The mass spectrometric fragmentation patterns of spirostanol saponins resemble those of furostanol saponins, as both typically undergo initial cleavage of the C3 glycosidic bond in the negative-ion mode. However, in positive-ion mode, spirostanol saponins undergo distinct sequential losses: first, the C3-linked sugar chain and then the hydroxyl groups. This pattern was exemplified by compounds such as (25 S )-POD-I ( 56 ) and polygodoraside A ( 72 ) ( Figure 8A and B ). Figure 8 Fragmentation pathways of ( A ) (25 S ) POD-I ( 56 ), ( B ) polygodoraside A ( 72 ). Image A depicts a pathway diagram with 2D skeletal line bond structures featuring a steroid-like core of four fused rings and a five-membered ring. Stereochemistry is indicated by wedge and dashed bonds, with sugar rings attached via O linkages. Arrows show stepwise losses: Xyl, Glc, Gal and a neutral loss of C6H10O2. Mass-to-charge ratios are 1031, 869, 737, 575 on the top row and 1033, 871, 739, 577 on the bottom row, with further losses to 415 and 271. Image B presents a similar diagram with the same core and sugar attachments. Losses are labeled Xyl, Glc, Gal and Xyl Glc, with additional arrows indicating minus H2O. Mass-to-charge ratios are 1225, 1093, 931, 769 on the top row and 1209, 1047, 885, 691 on the bottom row, with further losses to 429, 411 and 393. Two pathway diagrams A and B of 2D skeletal spirostanol saponins losing Xyl, Glc, Gal and water. Fragmentation pathways of ( A ) (25 S ) POD-I ( 56 ), ( B ) polygodoraside A ( 72 ). In the negative-ion mode, compound 56 was shown to undergo sequential loss of Xyl and Glc from the C-3 position in an outward to an inward manner. In the positive-ion mode, a base peak ion at m/z 1033 [M+H] + was generated along with a series of deglycosylated fragment ions, such as m/z 871 [M+H-Glc] + , 739 [M+H-Glc-Xyl] + , 577 [M+H-Glc-Xyl-Glc] + , and 415 [M+H-Glc-Xyl-Glc-Gal] + . Polygodoraside A ( 72 ) was found to undergo sequential outward to inward loss of Xyl and Glc from the C-3 position in the negative-ion mode. In the positive-ion mode, 72 yielded a base peak ion at m/z 1209 [M+H-H 2 O] + , accompanied by successive deglycosylation fragments, including m/z 1047 [M+H-H 2 O-Glc] + , 885 [M+H-H 2 O-Glc-Glc] + , 591 [M+H-H 2 O-Glc-Glc-Xyl-Glc] + , and 429 [M+H-H 2 O-Glc-Glc-Xyl-Glc-Gal] + . Based on these observations, it has been proposed that a glucose moiety is first eliminated from C-26, followed by cleavage of the sugar chain at C-3 in the positive-ion mode. This process ultimately generates the key aglycone ions at m/z 411 and 393, corresponding to [M+H-H 2 O-Glc-Glc-Xyl-Glc-Gal-H 2 O] + and [M+H-H 2 O-Glc-Glc-Xyl-Glc-Gal-H 2 O-H 2 O] + , respectively. With the key mass spectral fingerprints at m/z 415 and m/z 411 observed in positive-ion mode, compounds 56 and 72 were identified as types IV and V, respectively, according to the fragmentation pattern of steroidal saponins. The flavonoids of P. odoratum are predominantly homoisoflavonoids, with mass spectrometric fragmentation in the negative-ion mode combining classic flavonoid features with unique patterns. These compounds consistently generate the [M-H] − quasi-molecular ion, with fragmentation resulting from a Retro-Diels-Alder (RDA) reaction of the C-ring and cleavage at both sides of the methylene bridge connecting the B- and C-rings. 70 As an example, fragmentation of the representative disporopsin ( 96 ) ( Figure 9A ) begins with the RDA reaction in the C-ring, yielding conventional flavonoid fragments. A distinctive feature of homoisoflavonoids is the specific cleavage that occurs on both sides of the methylene bridge connecting the B- and C-rings; α -cleavage at the f-bond produces fragments such as m/z 179 [M-H-C 7 H 6 O 2 ] − (loss of p -hydroxycinnamoyl) and m/z 121 [M-H-C 9 H 8 O 4 ] − , whereas α-cleavage at the g-bond yields the m/z 191 [M-H-C 6 H 6 O 2 ] − fragment. The presence of both characteristic ion pairs, m/z 179 and 191, provides key evidence for the identification of P. odoratum homoisoflavonoids. 21 Figure 9 Fragmentation pathways of ( A ) disporopsin ( 96 ) and ( B ) N-trans -feruloyloctopamine ( 138 ). The red f and g represent the two α-cleavage sites of the methylene bridge connecting the B- and C-rings. The image A shows the fragmentation pathway of disporopsin. It begins with a structure having three six-membered rings with hydroxyl groups and a methylene bridge. The fragmentation occurs at two alpha-cleavage sites labeled f and g, resulting in fragments with m/z values of 179, 191 and 121. The image B shows the fragmentation pathway of feruloyloctopamine. It starts with a structure containing a six-membered ring and a side chain with methoxy and hydroxyl groups. The pathway involves the loss of water and other fragments, resulting in m/z values of 328, 310, 190, 161 and 132. Fragmentation pathways of disporopsin and feruloyloctopamine. Fragmentation pathways of ( A ) disporopsin ( 96 ) and ( B ) N-trans -feruloyloctopamine ( 138 ). The red f and g represent the two α-cleavage sites of the methylene bridge connecting the B- and C-rings. The alkaloids in P. odoratum are mainly amide alkaloids, such as p -coumaroyloctopamine and feruloyloctopamine, which exhibit clear fragmentation patterns in the negative-ion mode. These compounds initially form an [M-H] − quasi-molecular ion, which readily undergoes dehydration to yield an [M-H-H 2 O] − fragment. The core fragmentation mechanism is mediated by a McLafferty rearrangement adjacent to the α, β -unsaturated double bond of the amide group, causing the amide bond to cleave and generate characteristic acyl and amine moiety fragments, respectively. Using N-trans -feruloyloctopamine ( 138 ) as an example ( Figure 9B ), fragmentation initially produced an intermediate ion at m/z 190 [M-H-C 8 H 10 O 2 ] − , which further lost CHO to form the characteristic feruloyl ion at m/z 161, [M-H-C 8 H 10 O 2 -CHO] − . The concurrent rearrangement and cleavage of the acyl-N (amide) moiety of the dehydrated ion yielded the characteristic octopamine ion at m/z 132 [M-H-H 2 O-C 10 H 10 O 3 ] − . 21

Quality control of TCMs aims to ensure the consistency of medicinal material quality, efficacy, and safety. Given the complexity of TCM constituents, identifying their material basis is essential for establishing a scientific quality evaluation system. However, the current evaluation of P. odoratum in the Pharmacopoeia of the People’s Republic of China (2025 edition) mainly on polysaccharide content, which cannot fully represent its characteristic constituents and bioactive basis. Therefore, we predicted and evaluated the potential Q-markers of P. odoratum on the basis of specificity, traditional efficacy relevance, and measurability. P. odoratum exhibits distinct chemical characteristics compared with other medicinal species within the genus Polygonatum , including P. sibiricum, P. cyrtonema , and P. kingianum . Species-specific constituents are valuable candidates for Q-markers identification. LC-MS/MS analysis revealed that odoratumone A ( 86 ), 5,7-dihydroxy-6-methyl-8-methoxy-3-(4′-hydroxybenzyl)chroman-4-one ( 89 ), 5,7-dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)chroman-4-one ( 90 ), N-trans- feruloyloctopamine ( 138 ), and N-trans-p -coumaroyltyramine ( 139 ) were detected in P. odoratum but not in P. sibiricum . In addition, systematic interrogation of the fragmentation pathway of compound 138 was conducted in the MS section, lending support to its structural assignment and quality assessment. These results suggest that homoisoflavonoids and phenolic amides contribute to the chemical specificity of P. odoratum and may serve as potential Q-markers candidates, although further validation across multiple Polygonatum species is required. 136 Further comparative analysis of 60 batches from 11 Polygonatum species revealed that the 3-hydroxy homoisoflavonoid polygonatone B ( 111 ) and several dihydro-homoisoflavonoids with A-ring methoxyl substitutions were predominantly detected in P. odoratum , while they were not identified in other Polygonatum species. Moreover, approximately 83% of the reported homoisoflavonoids from the genus Polygonatum were derived from P. odoratum . These findings indicate that homoisoflavonoids possess high chemotaxonomic value and may serve as important chemical indicators for distinguishing P. odoratum from related Polygonatum species. 137 POPs also exhibit species-specific characteristics. HPGPC analysis showed that P. sibiricum, P. cyrtonema , and P. kingianum contained both a high-molecular-weight pectin fraction (P1, >4.1 × 10 5 Da) and a low-molecular-weight fructan fraction (P2, 2.8–5.4 × 10 3 Da), whereas only P2 was detected in P. odoratum . This distinct molecular weight distribution indicates that the polysaccharide profile of P. odoratum may serve as a characteristic feature for species discrimination. Therefore, homoisoflavonoids, phenolic amides, and characteristic polysaccharides all have potential as candidate Q-markers for P. odoratum . 138 From the perspective of pharmacological relevance, the traditional therapeutic effects of P. odoratum , including “promoting fluid production to relieve thirst” and “alleviating internal heat-induced thirst”, are closely associated with its modern pharmacological effects on glucose metabolism regulation. Among the identified constituents, homoisoflavonoids have been supported by relatively substantial pharmacological evidence. Compounds 91 and 92 were reported to enhance insulin-stimulated glucose uptake in 3T3-L1 adipocytes, suggesting their potential insulin-sensitizing activity. 34 In addition, sappanin-type homoisoflavonoids ( 89, 90 , and 98 ) were shown to inhibit GLUT2-mediated glucose transport. 77 Furthermore, compounds 99, 100, 101 , and 116 promoted AMPK activation, 43 further supporting the potential of homoisoflavonoids as candidate Q-markers for P. odoratum . The association between POPs and its traditional functions, such as nourishing yin, promoting fluid production, and relieving thirst, has also been supported by animal studies. YZ-2 isolated from P. odoratum , significantly reduced FBG, serum levels of TC, TG, LDL-C, and FINS levels in HFD/STZ-induced type 2 diabetes mellitus mouse model. 67 Beyond glucose metabolism-related activities, several characteristic phenolic amides from P. odoratum have also demonstrated biological effects associated with its traditional therapeutic properties. Integrated analysis based on weighted gene co-expression network analysis (WGCNA) and network pharmacology suggested that N-trans-p -coumaroyltyramine ( 139 ) may attenuate pulmonary fibrosis through the regulation of key targets, indicating a potential relationship between this compound and the traditional “nourishing yin and moistening dryness” function of P. odoratum . 122 Collectively, the pharmacological studies provide evidence supporting the potential of homoisoflavonoids, polysaccharides, and phenolic amides as candidate Q-markers of P. odoratum based on their association with the traditional therapeutic effects and related biological activities. Reliable quantitative methods are also essential for candidate Q-markers evaluation. Quantitative analysis of steroidal saponins was established based on systematic chemical profiling of P. odoratum using UHPLC-Q-TOF/MS. An UHPLC-CAD method was further developed for the absolute quantification of polygonatumoside F ( 19 ), timosaponin H1 ( 20 ), polygodoraside G ( 21 ), with contents ranging from 13.33–236.24, 50.55–545.04, and 13.34–407.83 μg/g, respectively. Notably, the content ratio of timosaponin H1 ( 20 ) to polygodoraside G ( 21 ) enabled discrimination between different commercial grades, with ratios generally 5 for Guanyuzhu , indicating its potential value for quality evaluation. 139 Early LC-MS studies also compared the composition and abundance of steroidal saponins in P. odoratum samples collected from different regions and harvesting periods. The results revealed variations in steroidal glycoside profiles and contents among samples. Notably, polygonatumoside F ( 19 ) and several other steroidal glycosides were present at relatively high levels, further supporting the feasibility of steroidal glycosides as chemical markers for P. odoratum . 27 Recent standard-assisted UHPLC-Q-Orbitrap-MS/MS analysis further identified 1-kestose in the medicinal underground parts of P. odoratum , with a content of 29.97 ± 0.06 μg/g. Quantitative validation across six samples from different geographical origins confirmed its detectability and medicinal-part specificity, supporting 1-kestose as a potential Q-markers candidate for P. odoratum . 140 In summary, Q-markers selection for P. odoratum should integrate plant-source specificity, traditional efficacy relevance, and chemical measurability. Current evidence suggests that homoisoflavonoids, steroidal saponins, polysaccharides, and certain phenolic amides possess potential as candidate Q-markers. Among them, polygonatumoside F ( 19 ), timosaponin H1 ( 20 ), polygodoraside G ( 21 ), and homoisoflavonoids are prioritized candidates, whereas 1-kestose shows promise due to its medicinal-part specificity and analytical feasibility. N-trans- feruloyloctopamine ( 138 ) and N-trans-p -coumaroyltyramine ( 139 ) may also serve as potential candidates. Although polysaccharides exhibit pharmacological relevance, their structural complexity limits their suitability as Q-markers. Further validation using multi-origin and multi-batch samples, together with spectrum–effect relationships, in vivo exposure characteristics, and dynamic changes during processing, is required to systematically evaluate candidate markers and establish a more robust Q-marker evaluation system for P. odoratum .

This review systematically summarizes the traditional applications, chemical constituents, mass spectrometric fragmentation patterns, pharmacological activities, Q-Marker prediction, and safety profile of P. odoratum , based on literature up to 2026 and encompassing over 170 small-molecule compounds and 18 polysaccharides. The fragmentation behaviors of representative compounds can be summarized as follows: steroidal saponins, classified into six types according to their aglycone skeletons, exhibit regular deglycosylation patterns; homoisoflavonoids display characteristic RDA cleavages and methylene bridge α-cleavage under negative-ion mode; and alkaloids predominantly undergo McLafferty rearrangement at amide bonds. These summarized fragmentation rules provide a reference for the rapid identification of related constituents in P. odoratum . Various P. odoratum extracts and monomers show hypoglycemic, immunomodulatory, anti-inflammatory, antioxidant, and antitumor activities. However, studies on structure–activity relationships are still weak, and most evidence comes from preclinical experiments, requiring further validation through well-designed clinical trials. Future work could combine LC-MS, network pharmacology, molecular docking, and functional validation to systematically investigate the mechanisms and structure–activity relationships, though predictions need experimental confirmation. In addition, the in vivo behavior of P. odoratum components and its relationship with efficacy is understudied and should be strengthened to solidify the material basis and improve quality evaluation. Based on Q-Marker prediction, homoisoflavonoids, polygonatumoside F ( 19 ), timosaponin H1 ( 20 ), polygodoraside G ( 21 ), N-trans-p -coumaroyltyramine ( 139 ), and 1-kestose are proposed as potential Q-Markers for P. odoratum , providing a theoretical basis for establishing a scientific quality evaluation method. Regarding safety, current data indicate no obvious toxicity at conventional doses, though heavy metal residues in certain samples and the potential risks of newly formed components during processing still warrant attention. In conclusion, future research should focus on the following aspects: first, conducting well-designed clinical studies to accumulate efficacy and safety data; second, strengthening structure–activity relationship investigations, as this area remains relatively weak; third, identifying characteristic chemical markers of P. odoratum through systematic multi-batch and multi-species comparisons to improve quality standards; and fourth, examining the impact of processing techniques on compositional transformation and safety. Progressive efforts in these directions will provide a more robust basis for the quality control and rational application of P. odoratum .

To ensure that the relevant literature was comprehensively retrieved, multiple key subject terms were systematically combined, including “traditional efficacy”, “chemical composition”, “steroidal saponins”, “flavonoids”, “alkaloids”, “polysaccharides”, “mass spectrometry fragmentation pathways”, “pharmacological activity”, “antidiabetic”, “antioxidant”, “immunomodulatory”, “antitumor”, “antibacterial and antiviral”, and “anti-obesity”, etc. These terms were paired with the target plant names “ Polygonatum odoratum (Mill). Druce”, without author citation “ Polygonatum odoratum ” and “Yuzhu”, covering both Chinese and English publications. The search was conducted across the following databases and resources: PubMed, Web of Science, SciFinder, CNKI, Wanfang Data, Google Scholar, and Pharmacopoeia of the People’s Republic of China (2025 edition). A total of 140 references published between 1984 and 2026 were included, covering journal articles, book chapters, online resources, and doctoral/master’s dissertations, with the content comprising both original research and review articles. We excluded unpublished papers and conference communications.

P. odoratum is an edible medicinal plant. According to the Pharmacopoeia of the People′s Republic of China (2025 edition), the recommended daily oral dose of P. odoratum is 6–12 g. It was classified as a superior-grade medicinal herb in Shen Nong Ben Cao Jing and no obvious toxicity has been documented in medica records. Modern studies have further supported its favorable safety profile. In vitro, the IC 50 of P. odoratum extract against NIH/3T3 fibroblasts was 26.6 mg/mL, indicating low cytotoxicity. Both the chick embryo chorioallantoic membrane assay and rabbit skin irritation test were negative, with no evident ocular irritation or skin corrosion/irritation. 126 POL showed no obvious cytotoxicity toward HELF and did not significantly induce apoptosis or autophagy. 105 Animal studies have likewise indicated low toxicity. The LD 50 of P. odoratum extract following intraperitoneal administration in mice was 14.5124 g/kg, corresponding to 14.5- and 2.9-fold the experimental effective and markedly effective doses, indicating a relatively wide safety margin. 127 Oral administration of P. odoratum aqueous extract to mice caused no obvious abnormalities or mortality, with an LD 50 >20 g/kg. In rats, 6-month administration produced no notable abnormalities in the examined parameters, except for transient soft stools in the high-dose group, which resolved after withdrawal. Moreover, the Ames test, bone marrow micronucleus and mouse sperm abnormality test showed no evident genotoxicity. 128 For the Huangqi – Sangye – Yuzhu granules, the maximum tolerated dose in mice following acute oral administration was >30.0 g/kg·BW, with no obvious acute toxicity; no adverse effects were observed in the 28-day repeated-dose study, and the no-observed-adverse-effect level (NOAEL) was 10.0 g/kg·BW. Collectively, these findings indicate that P. odoratum showed no evident cytotoxicity, acute toxicity, long-term toxicity, or genotoxicity at the doses investigated. 129 In addition to intrinsic toxicity, heavy metal and pesticide residues are important considerations in the safety evaluation of P. odoratum . The levels of Pb, Cd, As, Hg, and Cu in P. odoratum samples from different production areas were generally below the limits specified in the Pharmacopoeia of the People′s Republic of China (2025 edition), and residues of 33 prohibited pesticides were also within the prescribed limits. 130 However, combined exposure assessment of Pb, Cd, and as identified Cd exceedances in a small number of samples, while some samples had hazard index (HI) values >1. Using the target-organ toxicity dose (TTD) approach, HI values >1 were also observed for neurological and renal endpoints in some samples, indicating a potential risk from cumulative heavy metal exposure. Processing may also affect the safety profile of P. odoratum . 131 , 132 During processing, polysaccharide content decreased, whereas DDMP, 5-hydroxymethylfurfural (5-HMF), and Huangjing alkaloid A gradually formed, 133 with 5-HMF increasing with the degree of processing. High-dose exposure to 5-HMF may exert cytotoxic and genotoxic effects, therefore changes in its content should be considered in the safety evaluation of processed P. odoratum . 134 , 135 Overall, current toxicological evidence indicates that P. odoratum has relatively low overall toxicity. Nevertheless, cumulative heavy metal exposure and the formation of potentially harmful compounds during processing warrant further attention. As the available evidence is derived mainly from in vitro and animal studies, the long-term safety of high-dose human consumption remains to be established.

P. odoratum is used to nourish yin, counteract dryness, promote fluid production, and quench thirst. It is used clinically for conditions such as lung and stomach yin injury, dry-heat cough, throat dryness, thirst, consumptive fever, polyphagia with rapid hungering, frequent urination, and internal heat-induced thirst wasting. Classified as a superior grade herb in Shen Nong Ben Cao Jing, P. odoratum is commonly used as a medicinal substance in TCM formulations to treat wasting thirst. 13 It is effective for treating dry cough with scanty sputum and dry throat and tongue due to lung yin deficiency as well as symptoms that appear in the late stage of warm-heat diseases or after a high fever that consumes body fluids, including inadequate fluids, thirst, poor appetite, and gastric discomfort. It has also been reported to have therapeutic potential for treating conditions such as tuberculosis and cough. 14 Bencao Shiyi stated that P. odoratum primarily enhances intelligence, regulates qi and blood, strengthens the body, and is frequently used in formulas for treating menopause. 15 Rihuazi Bencao stated that P. odoratum alleviates vexation and fullness, quenches thirst, moistens the heart and lungs, and tonifies the five strains, seven injuries, and vacuity detriment. It primarily addresses qi stagnation in the heart and abdomen, vacuity heat, damp toxin lumbar pain, cold sensation in the stem center, eye pain, canthus erosion, and lacrimation. Long-term administration is believed to eliminate facial dark spots and pigmentation, improve complexion, enhance skin moisture and luster, and prevent aging. P. odoratum is a dual purpose medicinal and dietary tonic. Li Shizhen of the Ming Dynasty described his experience with its therapeutic effects in his Bencao Gangmu , “I have frequently employed it to treat consumptive diseases with alternating chills and fever, as well as all manner of ailments. Used as a substitute for ginseng and astragalus, it neither causes coldness nor dryness, and yields remarkable efficacy”. 2 Bencao Xinbian recorded P. odoratum as having a sweet taste and a slightly cold nature and stated that it entered the lung and stomach meridians. P. odoratum nourishes yin, moistens the lungs, tonifies the stomach, and promotes fluid production. It is primarily used for conditions such as the yin-deficient common cold, dry cough, consumptive cough, fluid injury in febrile diseases, and internal heat-induced wasting thirst. P. odoratum supplements yin; when combined with the root and rhizome of ginseng, which supplements yang, a complementary and synergistic balance is achieved. 15 Bencao Zhengyi noted that P. odoratum has demonstrated particularly rapid and effective results when treating conditions marked by blazing heat pathogens, excessive fire-generating wind, lung–stomach dryness, heat, exhaustion of body fluids, thirst and dry throat, and polyphagia with frequent hunger, and is thus applicable for treating symptoms arising. Additionally, P. odoratum has been used to improve myocardial hypoxia, enhance myocardial contractility, regulate heart rhythm, and dilate blood vessels; therefore, it can be used as an adjunctive treatment for tachycardia, premature beats, and heart failure management, 2 as illustrated in Figure 1 . P. odoratum is commonly used as a compatible herb in Mongolian medicine. Its effects include tonifying and strengthening the body, drying dampness, removing moisture, treating kidney-yang deficiency and cold syndrome, and fortifying the stomach. P. odoratum is used to regulate conditions that include general disability and kidney deficiency, spermatorrhea, lumbago and leg pain, kidney-yang deficiency and cold syndrome, gastric disorders, diarrhea with undigested food, frequent belching, and reduced stomach fire. P. odoratum also contributes to the alleviation of lower body coldness associated with Xie Ruwusu disease (a disorder of body fluid metabolism in Mongolian medicine), Heyi disease (a condition related to nervous system and mental functions in Mongolian medicine), and nutritional deficiency disorders. 16 Furthermore, it constitutes a significant compatible component in traditional Mongolian formulations such as yang-restoring pills. Based on the above, P. odoratum possesses the traditional therapeutic actions of nourishing yin, countering dryness, promoting fluid production, quenching thirst, supplementing deficiency, strengthening the body, and delaying aging. It is indicated for yin deficiency dry cough, thirst due to fluid depletion, wasting thirst, consumptive diseases, and yin deficiency disability. These traditional applications provide a clear direction for modern pharmacological research.

Understanding the phytochemical composition of medicinal plants is crucial for investigating their therapeutic potential. P. odoratum has been the subject of extensive research on its bioactive substances. Numerous compounds have been isolated from P. odoratum , including steroidal saponins, flavonoids, alkaloids, volatile oil constituents, polysaccharides, and others ( Figure 2 ). Figure 2 Chemical constituent classification of P. odoratum . The diagram illustrates the chemical constituents of P. odoratum, organized in a circular format. The central image shows plant roots. Surrounding sections include: Furostanol saponins, Cholestane saponins, Homoisoflavanones, Isoflavones, Flavonoids and Alkaloids. Each section contains chemical structures. The outer ring lists categories: Spirostanol saponins, Steroidal saponins, Volatile oil constituents, Polysaccharides, Acidic polysaccharides, Neutral polysaccharides and Others. The diagram highlights the diverse bioactive compounds found in P. odoratum. A diagram of chemical constituents in P. odoratum, including saponins, flavonoids, alkaloids and polysaccharides. Chemical constituent classification of P. odoratum . Steroidal saponins are considered one of the primary active constituents of P. odoratum and are commonly found in the Asparagaceae family. The steroidal saponin content in P. odoratum varies according to geographical origin, ranging from 0.094% to 0.278% among samples from 10 producing regions examined in study. 17 The highest content (0.2780%) was found in samples from Liaoning Province, whereas the lowest (0.0944%) was detected in samples from Heilongjiang Province. Steroidal saponins consist of six rings, with rings A, B, C, and D forming the steroidal core structure of cyclopentanoperhydrophenanthrene. This core generally contained four methyl groups. A double bond is often observed between C-5 and C-6. The C-12 position is generally unsubstituted or substituted with a carbonyl or hydroxyl group. The C-14 position is usually unsubstituted or substituted with a hydroxyl group and occasionally with a double bond. Based on the opening or closing of the F-ring, these saponins can be classified as either furostanol or spirostanol. 1 Furostanol saponins are formed when the F-ring of spirostanol saponins opens, and the 26-OH group is glycosylated. Depending on the absolute configuration of C-25, saponins can be further divided into 25 R and 25 S . Some steroidal saponins are mixtures of the 25 R and 25 S epimers. Spirostanol saponins feature a spiroketal structure at C-22, whereas the C-22 position in furostanol saponins is always substituted, typically with a hydroxyl group, methoxy group, or double bond. The sugar chains of steroidal saponins include glucose (Glc), galactose (Gal), xylose (Xyl), rhamnose (Rha), and arabinose (Ara). Furostanol saponins are typically glycosylated at C-3 and C-26. In spirostanol saponins, glycosylation typically occurs at C-3, and rarely at C-1 and C-24. 18 In this review, 83 steroidal saponins were isolated from P. odoratum , including cholestane ( 1 ‒ 10 ), furostanol ( 11 ‒ 38 ), and spirostanol ( 39 ‒ 83 ) saponins ( Table 1 ). Table 1 Chemical Compounds Isolated from Polygonatum odoratum (Mill.) Druce No. Compounds Type References Steroidal sapogenins and saponins 1 (22 S )-Cholest-5-ene-1 β ,3 β ,16 β ,22-tetraol 16- O-β -D-glucopyranoside Cholestane saponins [ 4 ] 2 (22 S )-Cholest-5-ene-1 β ,3 β ,16 β ,22-tetrol 1,16-di- O-β -D-glucopyranoside Cholestane saponins [ 4 ] 3 (22 S )-Cholest-5-ene-1 β ,3 β ,16 β ,22-tetrol-1- O-α -L-rhamnopyranosyl-16- O-β -D-glucopyranoside Cholestane saponins [ 18 ] 4 Polygodoside H Cholestane saponins [ 4 ] 5 (22 S )-16 β -[( α -L-rhamnopyranosyl)oxy]-3 β ,22-Dihydroxycholest-5-ene-1 β -yl α -L-rhamnopyranoside Cholestane saponins [ 4 ] 6 Polygoside C Cholestane saponins [ 18 , 19 ] 7 Polygoside D Cholestane saponins [ 18 , 19 ] 8 Polygoside E Cholestane saponins [ 18 , 19 ] 9 Polygonatumosides O Cholestane saponins [ 20 ] 10 Polygodoraside C Cholestane saponins [ 21 ] 11 26- O-β-D -glucopyranosyl-22- O -methyl-(25 S )-Furost-5-ene-3 β ,26-diol-3- O-β -D-glucopyranosyl(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl(1→4) β -D galactopyranoside Furostanol saponins [ 22 , 23 ] 12 26- O-β- D-glucopyranosyl-(25 S )-Furost-5-ene-3 β ,22,26-triol-3- O-β- D-glucopyranosyl(1→2)-[ β -D-xylopyranosyl-(1→3)]- β-D -glucopyranosyl(1→4) β -D-galactopyranoside Furostanol saponins [ 22 ] 13 3- O-β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)- β -D-galactopyranosyl 22-methoxy(25 R,S )-Furost-5-en-3 β ,14 α ,26-triol 26- O-β -D-glucopyranoside Furostanol saponins [ 24 ] 14 3- O-β -D-glucopyranosyl-(1→2)-[ β- D-glucopyranosyl-(1→3)]- β- D-glucopyranosyl-(1→4)- β -D-galactopyranosyl 22-methoxy-(25 R,S )-Furost-5-en-3 β ,14 α ,26-triol 26- O-β -D-glucopyranoside Furostanol saponins [ 24 ] 15 26- O-β -D-glucopyranosyl-(25 R,S )-Furost-5-ene-3 β ,14 α ,22 α ,26-quarol-3- O-β -D-glucopyranosyl(1→2)-[ β- D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl(1→4) β -D galactopyranoside Furostanol saponins [ 22 , 23 ] 16 Polyfuroside Furostanol saponins [ 25 ] 17 Polygonatumosides L Furostanol saponins [ 20 ] 18 25-Epi-officinalisnin II Furostanol saponins [ 21 ] 19 Polygonatumoside F Furostanol saponins [ 21 ] 20 Timosaponin H1 Furostanol saponins [ 21 ] 21 Polygodoraside G Furostanol saponins [ 21 , 26 ] 22 Polygodoraside H Furostanol saponins [ 21 ] 23 3- O-β- D-glucopyranosyl-(1→2)- β -D-glucopyranosyl-(1→4)- β -D-glucopyranoside Furostanol saponins [ 21 ] 24 Officinalisnin II Furostanol saponins [ 21 ] 25 Polygonatumoside G Furostanol saponins [ 27 ] 26 Funkioside B Furostanol saponins [ 27 ] 27 (25 S )-26-O- β -D-glucopyranosyl-furostane-5-ene-3 β ,22 α ,14 α ,26-tetrol-3-O- β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)- β -D-fucopyranoside Furostanol saponins [ 28 ] 28 (25 S )-26-O- β -D-glucopyranosyl-furostane-5-ene-3 β ,22 α ,14 α ,26-tetrol-3-O- β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)-6-acetyl- β -D-galactopyranoside Furostanol saponins [ 28 ] 29 (25 S )-26-O- β -D-glucopyranosyl-furostane-5-ene-3 β ,22 α ,14 α ,26-tetrol-3-O- β -D-glucopyranosyl-(1→2)- β -D-glucopyranosyl-(1→4)- β -D-fucopyranoside Furostanol saponins [ 28 ] 30 Polygonatumoside M Furostanol saponins [ 20 ] 31 Polygodoside G Furostanol saponins [ 4 , 21 ] 32 Polygonatumoside N Furostanol saponins [ 20 , 21 ] 33 Polygodoraside F Furostanol saponins [ 21 ] 34 (25 R )-Furost-5-en-12-one-3 β ,22,26-triol 26- O-β -D-glucopyranoside Furostanol saponins [ 29 ] 35 (25 S )-Furost-5-en-12-one-3 β ,22,26-triol 26- O-β -D-glucopyranoside Furostanol saponins [ 29 ] 36 26- O-β -D-glucopyranosyl-3 β ,26-dihydroxy-25( R )-∆5,22(23)-diene-Furost-3 -O -[ α -L-rhamnopyranosyl(1→2)]- α -L-rhamnopy-ranosyl(1→4)- β -D-glucopyranoside Furostanol saponins [ 22 ] 37 Typaspidoside H Furostanol saponins [ 21 ] 38 Polygodoraside D Furostanol saponins [ 21 ] 39 Neoprazefigenin A Spirostanol sapogenins [ 24 ] 40 3- O-β -D-glucopyranosyl-(1→2)-[ β -Dxylopyranosy1-(1-3)] -β -p-glucopyranosyl-(1-4) -β -D-galactopyranosy-(25 R, S )-Spirost-5-en-3 β , 14 α -diol Spirostanol saponins [ 24 ] 41 (25 R,S )-POD-I Spirostanol saponins [ 30 ] 42 Polygodoside A Spirostanol saponins [ 4 ] 43 Polygodoside B Spirostanol saponins [ 4 ] 44 Polygodoside D Spirostanol saponins [ 4 ] 45 Polygodoside E Spirostanol saponins [ 4 ] 46 Polygodoside F Spirostanol saponins [ 4 ] 47 Polygodosin A Spirostanol sapogenins [ 4 ] 48 PO-b Spirostanol saponins [ 4 ] 49 (25 R,S )-POD-IV Spirostanol saponins [ 4 , 30 ] 50 Spirost-5,25-diene-3 β ,14 α -diol-3-O- β -D-glucopyranosyl-(1→2)- β -D-glucopyranosyl-(1→4)- β -D-galactopyranoside Spirostanol saponins [ 28 ] 51 Spirost-5,25-diene-12-one-3 β ,14 α -diol-3-O- β -D-glucopyranosyl-(1→2)- β -D-glucopyranosyl-(1→4)- β -D-galactopyranoside Spirostanol saponins [ 28 ] 52 (25 S )-Spirosta-5-ene-3 β ,12 β -diol 3- O -{ β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)}- β -D-galactopyranoside Spirostanol saponins [ 31 , 32 ] 53 3 -O-β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosy1-(1→3)]- β -D-glucopyranosyl-(1→4)- β- D-galactopyranosyl yamogenin Spirostanol saponins [ 24 ] 54 Diosgenin Spirostanol sapogenins [ 30 ] 55 3 β ,14 α -dihydroxy-(25 S )-Sipirost-5-en Spirostanol sapogenins [ 19 , 22 ] 56 (25 S )-POD-I Spirostanol saponins [ 4 , 18 , 21 , 33 ] 57 3- O-β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)-galactopyranosy1-25( S )-Spirost-5(6),14(15)-dien-3 β -ol Spirostanol saponins [ 33 ] 58 Polygoside A Spirostanol saponins [ 19 , 27 ] 59 3 -O-β- D-glucopyranosyl-(1→2)-[ β- D-xylopyranosyl-(1→3)[- β- D-glucopyranosyl-(1→4)-galactopyranosy-25( S )-Spirost-5(6)-en-3 β ,14 α -diol Spirostanol saponins [ 18 , 19 , 27 , 33 ] 60 Polygonatumoside D Spirostanol saponins [ 18 , 19 ] 61 3- O-β -D-glucopyranoyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)- β -D-galacopyranosyl yamogenin Spirostanol saponins [ 27 ] 62 (25 S )-Spirost-5-ene-3 β -ol β -D-galactopyranoside Spirostanol saponins [ 4 ] 63 Yamogenin Spirostanol sapogenins [ 30 ] 64 Prazerigen Spirostanol sapogenins [ 22 , 30 ] 65 (25 R )-POD-II Spirostanol saponins [ 30 ] 66 Polygoside B Spirostanol saponins [ 19 ] 67 Polygonatumoside E Spirostanol saponins [ 18 ] 68 3 β -hydroxy-(25 S )-Spiriost-3- O-β -D-glucopyranosyl(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl(1→4) β -D-galactopyranoside Spirostanol saponins [ 22 ] 69 Polygodoside C Spirostanol saponins [ 4 ] 70 (25 S )-Spirost-5-ene-12-one-3 β ,14 α -diol-3- O - β -D-glucopyranosyl-(1→2)- β -D-glucopyranosyl-(1→4)- β -D-galactopyranoside Spirostanol saponins [ 28 ] 71 (25 R )-Spirost-5-ene-12-one-3 β ,14 α -diol-3- O - β -D-glucopyranosyl-(1→2)-[ β -D-glucopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)- β -D-galactopyranoside Spirostanol saponins [ 28 ] 72 Polygodoraside A Spirostanol saponins [ 21 ] 73 Polygodoraside B Spirostanol saponins [ 21 ] 74 3 β -hydroxy-25 S -Spiriost-3- O-β- D-glucopyranosyl(1→4) β- D-galactopyranoside Spirostanol saponins [ 22 ] 75 3 β -OH-(25 S )-Spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-arabinopyranoside Spirostanol saponins [ 22 ] 76 3 β -OH-(25 R )-Spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-arabinopyranoside Spirostanol saponins [ 22 ] 77 3 β -OH-(25 S )-Spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-galactopyranoside Spirostanol saponins [ 22 ] 78 3 β -OH-(25 R )-Spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-galactopyranoside Spirostanol saponins [ 22 ] 79 (25 S )-Spirosta-5,14-dien-3 β -ol 3- O -{ β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)}- β -D-galactopyranoside Spirostanol saponins [ 31 , 32 ] 80 Polygonatumoside K Spirostanol saponins [ 20 ] 81 Polygonatumoside H Spirostanol saponins [ 20 ] 82 Polygonatumoside I Spirostanol saponins [ 20 ] 83 Polygonatumoside J Spirostanol saponins [ 20 ] Flavonoids 84 5,7-Dihydroxy-6-methoxyl-8-methyl-3-(2′,4′-dihydroxybenzyl)chroman-4-one Homoisoflavanone [ 5 ] 85 5,7-Dihydroxy-6-methoxyl-3-(4-methoxybenzyl)-8-methylchroman-4-one Homoisoflavanone [ 5 ] 86 Odoratumone A Homoisoflavanone [ 31 , 32 , 34–36 ] 87 Odoratumone B Homoisoflavanone [ 36 ] 88 Methylophiopogonanone B Homoisoflavanone [ 34 ] 89 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4′-hydroxybenzyl)chroman-4-one Homoisoflavanone [ 31 , 32 , 34 , 35 , 37–39 ] 90 5,7-Dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)chroman-4-one Homoisoflavanone [ 32 , 34 , 35 , 37 ] 91 Ophiopogonanone E Homoisoflavanone [ 34 ] 92 (±)-5,7-Dihydroxy-6,8-dimethyl-3-(2′-hydroxy-4′-methoxybenzyl)chroman-4-one Homoisoflavanone [ 32 , 34 ] 93 Polygonatone A Homoisoflavanone [ 19 ] 94 3-(2,4-Dihydroxybenzyl)-5,7-dihydroxy-6-methylchroman-4-one Homoisoflavanone [ 5 , 40 ] 95 5,7-Dihydroxy-6-methyl-3-(4′-methoxybenzyl)-chroman-4-one Homoisoflavanone [ 41 ] 96 Disporopsin Homoisoflavanone [ 5 ] 97 5,7-Dihydroxy-3-(2′-hydroxy-4′-methoxybenzyl)-chroman-4-one Homoisoflavanone [ 34 ] 98 5,7,4′-Trihydroxy-6-methyl-dihydrohomoisoflavone Homoisoflavanone [ 32 , 38 ] 99 ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-6,8-dimethylchroman-4-one Homoisoflavanone [ 19 , 40–43 ] 100 ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-8-methoxy-6-methylchroman-4-one Homoisoflavanone [ 19 , 41–43 ] 101 ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-6-methylchroman-4-one Homoisoflavanone [ 19 , 41–44 ] 102 (3 R )-5,7-Dihydroxy-8-methyl-3-(2′,4′-dihydroxybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 103 (3 R )-5,7-Dihydroxy-8-methyl-3-(4′-hydroxybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 104 (3 R )-5,7-Dihydroxy-3-(2′-hydroxy-4′-methoxybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 105 (3 R )-5,7-Dihydroxy-3-(2′,4′-dihydroxyben-zyl)-chroman-4-one Homoisoflavanone [ 42 ] 106 (3 R )-5,7-Dihydroxy-3-(4′-hydroxybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 107 (3 R )-5,7-Dihydroxy-8-methoxy-3-(2′-hydroxy-4′-methoxybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 108 (3 R )-5,7-Dihydroxy-6-methyl-8-methoxy-3-(4′-methoxybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 109 (3 R )-5,7-Dihydroxy-6-methoxy-8-methyl-3-(2′,4′-dihydro-xybenzyl)-chroman-4-one Homoisoflavanone [ 42 ] 110 5,7-Dihydroxy-6,8-dimethyl-3( R,S )-(3′-hydroxy-4′-methoxybenzyl)chroman-4-one Homoisoflavanone [ 34 ] 111 Polygonatone B Homoisoflavanone [ 19 ] 112 Polygonatone C Homoisoflavanone [ 19 ] 113 ( E )-5,7-Dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzylidene)-chroman-4-one Homoisoflavanone [ 34 ] 114 ( E )-3-(3,4-Dihydroxybenzylidene)-5,7-dihydroxy-6,8-dimethylchroman-4-one Homoisoflavanone [ 45 ] 115 ( E )-3-(3,4-Dihydroxybenzylidene)-5,7-dihydroxy-8-methoxy-6-methylchroman-4-one Homoisoflavanone [ 45 ] 116 Polygonatone D Homoisoflavanone [ 19 , 43 ] 117 4′-Demethylleucomin 7- O-β -D-glucopyranoside Homoisoflavanone [ 34 ] 118 Yuzhusu A Homoisoflavanone [ 46 ] 119 Yuzhusu B Homoisoflavanone [ 46 ] 120 Yuzhusu C Homoisoflavanone [ 46 ] 121 Yuzhusu D Homoisoflavanone [ 46 ] 122 5,7,4′-Trihydroxy isoflavone Isoflavonoid [ 40 ] 123 5,7,4′-Trihydroxy-6-methoxy isoflavone Isoflavonoid [ 40 ] 124 5,7,4′-Trihydroxy-6,3′-dimethoxy isoflavone Isoflavonoid [ 40 ] 125 Tectoridin Isoflavonoid [ 34 ] 126 5,4′-Dihydroxy-7-methoxy-6-methylflavane Flavonoid [ 19 ] 127 Naringenin Flavonoid [ 47 ] 128 Catechin Flavonoid [ 47 ] 129 Nobiletin Flavonoid [ 47 ] 130 Hesperetin 7-rutinoside Flavonoid [ 34 ] 131 Isoquercitrin Flavonoid [ 47 ] 132 Quercetin 3- O-β -D-glucuronide Flavonoid [ 47 ] 133 Astragalin Flavonoid [ 47 ] 134 Kaempferol-7- O-β -D-glucopyranoside Flavonoid [ 47 ] 135 Kaempferol 3-sambubioside Flavonoid [ 47 ] Alkaloids 136 N-cis -Feruloyloctopamine Alkaloid [ 20 ] 137 N-trans-p -Coumaroyloctopamine Alkaloid [ 20 , 48 ] 138 N-trans -Feruloyloctopamine Alkaloid [ 19 , 20 , 48 ] 139 N-trans-p -Coumaroyltyramine Alkaloid [ 20 ] 140 N-trans -Feruloyltyramine Alkaloid [ 20 ] 141 3-Ethoxymethyl-5,6,7,8-tetrahydroindolizin-8-one Alkaloid [ 31 ] 142 1-Deoxynojirimycin Alkaloid [ 49 ] 143 Fagomine Alkaloid [ 49 ] Others 144 L-azetidine-2-carboxylic acid Amino acid analogue [ 49 ] 145 (2 S )-Citrullinamide Amino acid analogue [ 49 ] 146 Serine Amino acid [ 49 ] 147 4-Aminobutyric acid Amino acid [ 49 ] 148 Betaine Amino acid analogue [ 49 ] 149 β -Sitosterol Steroid [ 22 ] 150 Daucosterol Steroid [ 22 ] 151 3 β ,19 α -Dihydroxyurs-12-en-24,28-dioic acid Triterpenoid [ 40 ] 152 Zizybeoside I Glycoside [ 22 , 23 ] 153 Emodin-8- O-β -D-glucopyranoside Anthraquinone [ 19 ] 154 Emodin Anthraquinone [ 50 ] 155 Physcion Anthraquinone [ 50 ] 156 Polygodoquinone A Anthraquinone [ 50 ] 157 p -Hydroxybenzoic acid Phenol [ 19 ] 158 ( E )-3-(4-hydroxy-3-methoxybenzylidene)-4-(4-hydroxyphenyl)Pyrrolidin-2-one Phenol [ 48 ] 159 3-(4-hydroxy-3-methoxy-phenyl)-Acrylic acid carboxymethyl ester Phenol [ 48 ] 160 (±)-Syringaresinol Lignan [ 40 ] 161 (±)-Syringaresinol- O-β -D-glucopyranoside Lignan [ 40 ] 162 Liriodendrin Lignan [ 40 ] 163 1,8-Suberic acid Fatty acid [ 40 ] 164 1,9-Azelaic acid Fatty acid [ 40 ] Volatile oil constituents 165 Pentadecane Volatile oil constituent [ 51 ] 166 2-Nonanol Volatile oil constituent [ 52 ] 167 Geranylacetone Volatile oil constituent [ 51 ] 168 Hexanal Volatile oil constituent [ 51 ] 169 2-Octanone Volatile oil constituent [ 52 ] 170 Cedrol Volatile oil constituent [ 51 ] 171 9-Cedranone Volatile oil constituent [ 7 ] 172 3-Methoxy-2,5,6-trimethylphenol Volatile oil constituent [ 7 ] 173 Limonene Volatile oil constituent [ 51 ] 174 Paeonol Volatile oil constituent [ 53 ] Note : →: glycosidic linkage direction (non-reducing → reducing end). Chemical Compounds Isolated from Polygonatum odoratum (Mill.) Druce Note : →: glycosidic linkage direction (non-reducing → reducing end). Cholestanol saponins are a category of steroidal saponins that are characterized by a core structure of cyclopentanoperhydrophenanthrene comprising four fused rings (A, B, C, and D). Cholestanol saponins are precursors of furostanol and spirostanol saponins. Specifically, (22 S )-cholest-5-ene-1 β ,3 β ,16 β ,22-tetraol 16- O-β -D-glucopyranoside ( 1 ), (22 S )-cholest-5-ene-1 β ,3 β ,16 β ,22-tetrol 1,16-di- O-β -D-glucopyranoside ( 2 ), (22 S )-cholest-5-ene-1 β ,3 β ,16 β ,22-tetrol-1- O-α -L-rhamnopyranosyl-16- O-β -D-glucopyranoside ( 3 ), polygodoside H ( 4 ), and (22 S )-16 β -[( α -L-rhamnopyranosyl)oxy]-3 β ,22-dihydroxycholest-5-ene-1 β -yl α -L-rhamnopyranoside ( 5 ) were potential intermediates in the biosynthesis of furostanol and spirostanol saponins. 4 , 18 The structures of cholestane saponins are shown in Figure 3A . Figure 3 Structures of ( A ) cholestanol saponins ( 1 ‒ 10 ), ( B ) furostanol saponins ( 11 ‒ 38 ), and ( C ) spirostanol saponins ( 39 ‒ 83 ) isolated from P. odoratum . The red A and E represent the A ring and E ring of steroidal saponins, respectively. S 1 –S 6 represent different glycosyl substituents. The image contains three panels labeled A, B and C, each showing chemical structures of steroidal saponins. Panel A depicts cholestanol saponins with a core structure of cyclopentanoperhydrophenanthrene comprising four fused rings labeled A, B, C and D. Structures include various glycosyl substituents such as glucopyranoside and rhamnopyranoside. Panel B illustrates furostanol saponins, featuring similar core structures with additional substituents and variations in glycosyl groups. Panel C presents spirostanol saponins, showing further structural variations and glycosyl substitutions. Each panel includes multiple compounds with specific substituents and configurations, highlighting the diversity within each saponin category. The structures are annotated with labels indicating different substituents and positions, such as R groups and hydroxyl groups. Structures of cholestanol, furostanol and spirostanol saponins in three panels. Abbreviations : Xyl, xylopyranosyl; Glc, glucopyranosyl; Gal, galactopyranosyl. Structures of ( A ) cholestanol saponins ( 1 ‒ 10 ), ( B ) furostanol saponins ( 11 ‒ 38 ), and ( C ) spirostanol saponins ( 39 ‒ 83 ) isolated from P. odoratum . The red A and E represent the A ring and E ring of steroidal saponins, respectively. S 1 –S 6 represent different glycosyl substituents. The structure of furostanol saponins comprises five fused rings (A, B, C, D, and E) and an open F ring. The stereochemistry at the C-25 position could be either R or S . In P. odoratum , furostanol saponins are typically bisdesmosidic, featuring a sugar chain at the C-3 position and, invariably, a D-glucose residue at the C-26 position. Most furostanol saponins contain only one double bond between C-5 and C-6 ( 11 ‒ 26 ). Some furostanol saponins have unsaturated bonds between C-20 and C-22, such as polygonatumoside M ( 30 ), polygodoside G ( 31 ), polygonatumoside N ( 32 ), and polygodoraside F ( 33 ), 4 , 20 , 21 or between C-22 and C-23, such as 26- O-β -D-glucopyranosyl-3 β ,26-dihydroxy-25( R )-∆5,22(23)-diene-furost-3- O -[ α -L-rhamnopyranosyl(1→2)]- α -L-rhamnopy-ranosyl(1→4)- β -D-glucopyranoside ( 36 ), typaspidoside H ( 37 ), and polygodoraside D ( 38 ). 21 , 22 Carbonyl substitution occurs infrequently, such as in (25 S )-furost-5-en-12-one-3 β ,22,26-triol 26 -O-β -D-glucopyranoside ( 35 ) and (25 R )-furost-5-en-12-one-3 β ,22,26-triol 26- O-β -D-glucopyranoside ( 34 ). 29 The structures of furostanol saponins are shown in Figure 3B . Spirostanol saponins are found in nearly every species of the Polygonatum genus. Their structure also consists of five fused rings (A, B, C, D, and E) and an F-ring attached at C-22 in a spiro linkage. 54 The double bond is typically present between C-5 and C-6 and occurs less frequently at the C-25 position, such as in polygodoside A ( 42 ) and polygodoside B ( 43 ). 4 Carbonylation is usually observed at the C-12 position, as exemplified by the compounds 3 β -hydroxy-(25 S )-spiriost-3- O-β -D-glucopyranosyl(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl(1→4) β- D-galactopyranoside ( 68 ), polygodoside C ( 69 ), and 3 β -hydroxy-25 S -spiriost-3- O-β -D-glucopyranosyl(1→4) β- D galactopyranoside ( 74 ). 4 , 22 Glycosylation typically occurs at the C-3 position; however, it is occasionally observed at C-1, similar to 3 β -OH-(25 S )-spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-arabinopyranoside ( 75 ), 3 β -OH-(25 R )-spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α- L-arabinopyranoside ( 76 ), 3 β -OH-(25 S )-spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-galactopyranoside ( 77 ), and 3 β -OH-(25 R )-spiriost-1- O-α -L-rhamnopyranosyl-(1→2)- α -L-galactopyranoside ( 78 ). 20 , 22 The structures of spirostanol saponins are shown in Figure 3C . In this review, 52 flavonoids ( 84 ‒ 135 ) were identified that have been isolated from P. odoratum . Flavonoids typically have a C6–C3–C6 structural skeleton characterized by two benzene rings (A and B) connected by a three-carbon chain. The three-carbon chain forms an oxygen-containing heterocyclic ring with the A-ring, known as the C-ring, which is the γ -pyran ring in most flavonoids. Most flavonoids isolated from P. odoratum are homoisoflavonoids, which serve as the key material basis for their antioxidant, hypoglycemic, and anti-inflammatory effects. Their core structure differs from that of typical flavonoids because of the additional carbon atom in the C-ring. The C-3 position is connected to the B-ring, which is a chiral center. The A-ring commonly undergoes hydroxyl substitution at the C-5 and C-7 positions; these two hydroxyl groups are in the meta position and form a stable hydrogen-bond chelation system. Furthermore, substitutions by hydroxyl, methoxy, or methyl groups at C-6 and C-8 are common. The B-ring often undergoes random oxygenation at the C-2′, C-3′, and C-4′ positions. The position of the B-ring attachment defines the flavonoid subclass and is attached at C-3 in isoflavonoids, such as 5,7,4′-trihydroxy isoflavone ( 122 ), 5,7,4′-trihydroxy-6-methoxy isoflavone ( 123 ), 5,7,4′-trihydroxy-6,3′-dimethoxy isoflavone ( 124 ), and tectoridin ( 125 ). 34 , 40 The structures of flavonoids are shown in Figure 4A . Figure 4 Structures of ( A ) flavonoids ( 84 ‒ 135 ) and ( B ) alkaloids ( 136 ‒ 143 ) isolated from P. odoratum . The red A, B, and C represent the A ring, B ring, and C ring of flavonoids, respectively. Section A features flavonoid structures with three connected rings: A and B are benzene rings and C is a six-membered ring with oxygen and a carbonyl group. Structures are numbered 84-135, with substituents like H, OH, OCH3 and CH3 labeled as R1, R2, R3 and R4. Some compounds have sugar rings attached to the flavonoid core, showing stereochemistry with wedge and dashed bonds. Section B includes alkaloid structures numbered 136-143. Compound 136 and series 137-140 consist of two benzene rings linked by a chain with a carbonyl and NH group, featuring phenolic OH and methoxy substituents. Compounds 137-140 have R1 and R2 labels with substituents. Compound 141 is a bicyclic system with a carbonyl and ring nitrogen, plus an O-linked side chain. Compounds 142 and 143 are small nitrogen rings with multiple OH groups, showing stereochemistry with wedge and dashed bonds. Two-part figure of 2D skeletal flavonoid and alkaloid structures numbered 84 to 143 with R group tables. Structures of ( A ) flavonoids ( 84 ‒ 135 ) and ( B ) alkaloids ( 136 ‒ 143 ) isolated from P. odoratum . The red A, B, and C represent the A ring, B ring, and C ring of flavonoids, respectively. Although relatively few alkaloids have been isolated from P. odoratum , they exhibit potent α-glucosidase inhibitory activity and serve as important substances contributing to its hypoglycemic efficacy. The primary alkaloids identified were N-cis -feruloyloctopamine ( 136 ), N-trans-p- coumaroyloctopamine ( 137 ), N-trans -feruloyloctopamine ( 138 ), N-trans-p- coumaroyltyramine ( 139 ), N-trans -feruloyltyramine ( 140 ), 20 , 48 3-ethoxymethyl-5,6,7,8-tetrahydroindolizin-8-one ( 141 ), 1-deoxynojirimycin ( 142 ), fagomine ( 143 ). 31 , 49 Additionally, on a C 18 column, the retention time of the 136 cis isomer is generally shorter than that of the trans isomer 138 , enabling their differentiation and identification. 21 The structures of alkaloids are shown in Figure 4B . In addition, other chemical species ( 144 ‒ 164 ) have been isolated from P. odoratum . These include amino acids and their analogues, including l-azetidine-2-carboxylic acid ( 144 ), (2 S )-citrullinamide ( 145 ), serine ( 146 ), 4-aminobutyric acid ( 147 ), and betaine ( 148 ); 49 steroids, including β -sitosterol ( 149 ) and daucosterol ( 150 ); 22 a triterpenoid 3 β ,19 α -dihydroxyurs-12-en-24,28-dioic acid ( 151 ); 40 a glycoside zizybeoside I ( 152 ); anthraquinones, including emodin-8- O-β -D-glucopyranoside ( 153 ), 19 emodin ( 154 ), physcion ( 155 ), and polygodoquinone A ( 156 ); 48 the phenols p -hydroxybenzoic acid ( 157 ), 19 ( E )-3-(4-hydroxy-3-methoxybenzylidene)-4-(4-hydroxyphenyl)pyrrolidin-2-one ( 158 ), and 3-(4-hydroxy-3-methoxy-phenyl)-acrylic acid carboxymethyl ester ( 159 ); 48 the lignans (±)-syringaresinol ( 160 ), (±)-syringaresinol- O-β -D-glucopyranoside ( 161 ), and liriodendrin ( 162 ); and fatty acids, including 1,8-suberic acid ( 163 ) and 1,9-azelaic acid ( 164 ). 40 The structures of compounds 144 ‒ 164 isolated from P. odoratum are shown in Figure 5A . Figure 5 Structures of ( A ) compounds ( 144 ‒ 164 ) and ( B ) volatile oil constituents ( 165 ‒ 174 ) isolated from P. odoratum . A 1 : β -D-Glucopyranosyl. Panel A illustrates 2D skeletal formulas of compounds 144 to 164, featuring amino acids like l-azetidine-2-carboxylic acid (144) and serine (146), steroids such as beta-sitosterol (149) and anthraquinones like emodin (154). Phenols include p-hydroxybenzoic acid (157), while lignans like syringaresinol (160) are shown with sugar substituents. Fatty acids such as suberic acid (163) are depicted with carboxylic groups. Panel B presents volatile oil constituents 165 to 174, including hydrocarbons, alcohols and ketones. Terpenes like compounds 170 and 171 are detailed with stereochemistry and aromatic compounds such as 172 and 173 feature methoxy and hydroxyl groups. Compound 174 is a benzene ring with a ketone group. The image highlights R group variations and sugar substituents, offering detailed structural insights for each compound. 2D formulas of amino acids, steroids, anthraquinones, phenols, lignans and fatty acids. Structures of ( A ) compounds ( 144 ‒ 164 ) and ( B ) volatile oil constituents ( 165 ‒ 174 ) isolated from P. odoratum . A 1 : β -D-Glucopyranosyl. The volatile oil constituents of P. odoratum are obtained by methods such as hydrodistillation or solvent extraction, and its chemical composition is typically characterized by GC–MS. The major volatile oil constituents are generally low-molecular-weight, volatile compounds, including monoterpenes, sesquiterpenes, and other volatile aromatic or aliphatic compounds. 55 , 56 The composition of the volatile oil constituents may vary depending on extraction conditions, cultivar, and plant part. GC–MS analyses have identified several low-molecular-weight volatile oil constituents in P. odoratum , including pentadecane ( 165 ), 2-nonanol ( 166 ), geranylacetone ( 167 ), hexanal ( 168 ), 2-octanone ( 169 ), cedrol ( 170 ), 9-cedranone ( 171 ), 3-methoxy-2,5,6-trimethylphenol ( 172 ), limonene ( 173 ), and paeonol ( 174 ). 51–53 Among these compounds, geranylacetone ( 167 ), and pentadecane ( 165 ) were predominant in the roots, whereas limonene ( 173 ) and geranylacetone ( 167 ) were predominant in the stems; limonene ( 173 ) was also the major volatile compound in the leaves. Paeonol ( 174 ) was reported as a characteristic component of the cultivar “Da Yuzhu”. 53 The chemical structures of the reported volatile compounds are shown in Figure 5B . P. odoratum polysaccharides (POPs) are high in content, safe, and possess a broad spectrum of biological activities, serving as the core macromolecular active constituents that mediate immunomodulatory, hypoglycemic, antioxidant, and anti-aging effects. Polysaccharides are high molecular weight carbohydrates formed by glycosidic bonds that link more than ten monosaccharide units. Polysaccharides, constituting 6.51–10.27% of the content in P. odoratum , are recognized as one of the primary active components. 57 , 58 The primary methods for extracting these polysaccharides include water, ultrasound-assisted extraction, 59 , 60 enzyme-assisted extraction, 61 and microwave-assisted extraction. 62 Common decolorization methods include oxidation, adsorption, and ion exchange. Deproteinization is typically achieved using the Sevag method, trifluorotrichloroethane method, or trichloroacetic acid method. Polysaccharides are often purified using column chromatography techniques, such as DEAE-52 cellulose column chromatography and Sephadex G-100 gel filtration chromatography. 63 Common structural characterization techniques include high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), periodate oxidation and Smith degradation, methylation analyses, Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, GC-MS, and scanning electron microscopy (SEM). 63 In total, 18 distinct polysaccharides that have been isolated and purified from P. odoratum are presented in Table 2 . These polysaccharides vary in their monosaccharide composition: most contain Man, Glu, and Ara, whereas a minority contain fucose. Based on differences in monosaccharide composition, they can be further categorized into neutral and acidic polysaccharides. Neutral polysaccharides, which lack uronic acids, include POP1, NPOP60-I, POB-2-2, POB-2-3, CPP, HPP, YZ-2, POPs, and POA-70S. Polysaccharides containing uronic acids are acidic, as exemplified by POAP80, POAP60-I, POA-70P, PORPs, POB-2-1 and PORP-1. The structures of POB-2-1, POB-2-2, and POB-2-3 are shown in Figure 6 . Table 2 Polysaccharides Isolated from P. odoratum Polysaccharides Monosaccharide Composition The Linkage of Sugar Type of Polysaccharides References Neutral polysaccharides Man:Glc = 5:1 N/A Neutral [ 8 ] POP1 Glu, Man →1)- β -D-Fru f -(2→, →6)- β -D-Fru f -(2→, →1,6)- β -D-Fru f -(2→, β -D-Fru f -(2→, and ɑ -D-Man. Neutral [ 64 ] POAP80 Man:Glc:GalA:Gal = 0.93:2.65:29.38:3.47 N/A Acidic [ 57 ] NPOP60-I Man:Glc:Gal = 1.00:12.07:9.55 →6)-Glc-(1→, →6)-Gal-(1→, →2)-Glc-(1→ Neutral [ 61 ] POAP60-I Man:Rha:GalA:Glc:Gal:Ara = 1.00:0.82:0.22:12.61:4.87:2.23 →6)-Glc-(1→, →4)-Glc-(1→, →6)-Gal-(1→, →6)-Man-(2→ Acidic [ 61 ] CPP Man:Glu:Rha:Glc:Gal:Ara = 7.80:1.08:1.63:65.93:3.58:1.00 N/A Neutral [ 65 ] HPP Man:Glu:Rha:Glc:Gal:Ara = 11.22:0.23:0.23:17.59:2.73:9.10 N/A Neutral [ 65 ] POPs Fru:Ara:Glc:Gal:Xyl = 87.72:0.30:11.56:0.19:0.23 N/A Neutral [ 66 ] YZ-2 Man:Glc:Gal:Ara = 1.000:1.995:0.334:0.074 →3)-Glc-(1→, →2,3,4)-Glc-(1→, →2,3,4)-Gal-(1→, →2)-Man-(1→ Neutral [ 67 ] POA-70S Fru:Glc:Fuc:Man = 69.05:3.85:2.65:0.30 Fru f -(2→, D-Glc p -(1→, →6)-Fru f -(2→, →2)-Fru f -(1→ Neutral [ 68 ] POA-70P Man:Ara:Fac:Glc:GalA = 36.67:1.63:8.73:5.36:0.99 D-Man p -(l→, D-Gal p -(1→, →4)-Man p -(1→, →4)-Gal p -(1→, →4)-Glc p -(1→, →3,6)-Gal p -(1→ Acidic [ 68 ] POB-2-1 Glc, GlcA, Ara →5)- α -L-Ara f -(1→, →4)- β -D-GlcA p -(1→, →2,6)- β -D-Gal p -(1→, α -L-Ara f -(1→, α -D-Glc p -(1→ Acidic [ 69 ] POB-2-2 Gal, Ara α -L-Ara f -(1→, α -D-Gal p -(1→, →4)- β -D-Gal p -(1→, →3,6)- β -D-Gal p -(1→, →2,5)- α -L-Ara f -(1→ Neutral [ 69 ] POB-2-3 Rha, Glc, Ara →2)- α -L-Rha p -(1→, →4)- β -D-Glc p -(1→, →2,3)- β -D-Gal p -(1→, α -L-Ara f -(1→, α -D-Glc p -(1→ Neutral [ 69 ] PORPs Man:GlcA:GalA:Glc:Ara:Fuc = 18.30:0.81:1.46:41.83:1.53:1.06 N/A Acidic [ 63 ] PORP-1 Man:GlcA:Glc:Ara:Fuc = 19.28:0.41:39.76:1.54:1.08 →6)- α -D-Glc p -(1→, α -Glc p -(1→, →4,6)- α -D-Glc p -(1→, →4)- β -D-Man-(1→, →3)- α -D-Man p -(1→ Acidic [ 63 ] SPORP-1 N/A N/A Acidic [ 63 ] SPORP-2 N/A N/A Acidic [ 63 ] Note : N/A = data not available. →: glycosidic linkage direction (non-reducing → reducing end). Abbreviations : Man, Mannose; Rha, Rhamnose; GlcA, Glucuronic acid; GalA, Galacturonic acid; Glc, Glucose; Gal, Galactose; Xyl, Xylose; Ara, Arabinose; Fuc, Fucose; Fru, Fructose; Ara f , Arabinofuranose; Glc f , Glucofuranose; Glc p , Glucopyranose; Fru f , Fructofuranose; Gal p , Galactopyranose; Man p , Mannopyranose; GlcA p , Glucopyranuronic acid; Rha p , Rhamnopyranose. Figure 6 Structures of POB-2-1, POB-2-2, and POB-2-3 isolated from P. odoratum . Three polysaccharide schematics, POB-2-1, POB-2-3 and POB-2-2, feature Haworth-style sugar rings with in-ring oxygen atoms and glycosidic linkers. Each schematic has repeating units indicated by curly braces. POB-2-1 and POB-2-3 display similar top chains with Residues D, E, F and A marked by arrows. Both have a downward branch labeled Residue B. POB-2-3 includes an OAc substituent in the lower branch. POB-2-2 differs with a vertical segment of two connected sugar rings, marked by arrows for Residues E, D and A. A separate short chain shows Residue F and B with arrows. No linkage positions are specified. Two dimensional glycan ring drawings of POB-2-1, POB-2-2 and POB-2-3 with residues A to F. Abbreviations : POB-2-1, Residue A: α -L-Ara f -(1→, Residue B: α -D-Glc p -(1→, Residue D: →5)- α -L-Ara f -(1→, Residue E: →4)- β -D-GlcA p -(1→, Residue F: →2,6)- β -D-Gal p -(1→. POB-2-2, Residue A: 2-OAc- α -L-Ara f -(1→, Residue B: α -D-Gal p -(1→, Residue D: →4)- β -D-Gla p -(1→, Residue E: →3,6)- β -D-Gal p -(1→, Residue F: →2,5)- α -L-Ara f -(1→. POB-2-3, Residue A: α -L-Ara f -(1→, Residue B: 3-OAc- α -D-Glc p -(1→, Residue D: →2)- α -L-Rha p -(1→, Residue E: →4)- β -D-Glc p -(1→, Residue F: →2,3)- β -D-Gal p -(1→. Polysaccharides Isolated from P. odoratum Note : N/A = data not available. →: glycosidic linkage direction (non-reducing → reducing end). Abbreviations : Man, Mannose; Rha, Rhamnose; GlcA, Glucuronic acid; GalA, Galacturonic acid; Glc, Glucose; Gal, Galactose; Xyl, Xylose; Ara, Arabinose; Fuc, Fucose; Fru, Fructose; Ara f , Arabinofuranose; Glc f , Glucofuranose; Glc p , Glucopyranose; Fru f , Fructofuranose; Gal p , Galactopyranose; Man p , Mannopyranose; GlcA p , Glucopyranuronic acid; Rha p , Rhamnopyranose. Structures of POB-2-1, POB-2-2, and POB-2-3 isolated from P. odoratum .

P. odoratum contains steroidal saponins, flavonoids, alkaloids, polysaccharides, and others with pharmacological activities including antidiabetic, anti-inflammatory, antioxidant, and antitumor effects ( Figure 10 ). Figure 10 Molecular mechanisms underlying the pharmacological effects of P. odoratum . An infographic details the molecular mechanisms of P. odoratum′s pharmacological effects. At the center, a plant image is labeled with four compound classes: Alkaloids, Polysaccharides, Flavonoids and Steroidal saponins, each with a chemical structure. Surrounding are organ icons and cell lines: 3T3-L1, Hela, A549, BEAS-2B, RAW 264.7, BV2, A375; Breast: MDA-MB-231, MCF-7, T47D; Stomach: BGC-823, SGC-7901, CL-187; Kidney: 293T, Vero; Liver: HepG2; Intestines: Caco-2, HuTu-80, CL-187. Arrows indicate upregulation and downregulation. Activity sections: Anti-diabetic effects include IFN-gamma, MDA, NF-kappaB down, IL-4, IL-10, SOD, Nrf2 up. Anti-tumor effects show p-Bcl-2, p53, p-p38, p-Cdc2 up, Bcl-2, Cdc2 down. Anti-inflammatory effects list IL-1beta, IL-6, TNF-alpha, IFN-gamma down, IL-10, IL-4 up. Anti-oxidant effects include MDA, ROS down, SOD, CAT, GSH-Px up. An infographic of Polygonatum odoratum compounds and bioactivities across organs and cell lines. Molecular mechanisms underlying the pharmacological effects of P. odoratum . The traditional efficacy of P. odoratum in “promoting fluid production, relieving thirst, and treating wasting-thirst disorder” is highly consistent with its modern pharmacological effects, including lowering blood glucose, improving insulin resistance, and preventing and treating diabetic complications. P. odoratum aqueous extracts have been shown to exert hypoglycemic effects by inhibiting α-glucosidase activity and regulating glucose and lipid metabolism pathways ( Table 3 ). 71 The ethanol extracts of P. odoratum have been reported to lower blood glucose through multiple mechanisms: restoration of the CD 4 + /CD 8 + T cell balance, 46 modulation of related cytokine levels, 72 inhibition of advanced glycation end products (AGEs) formation in the renal cortex, 73 and suppression of Th1 cell polarization to mitigate immune-mediated damage to pancreatic β-cells in type 1 diabetic mice. 74 Furthermore, in high-fat diet (HFD)-induced C57BL/6 mice, P. odoratum ameliorated metabolic disorders by reducing fasting blood glucose (FBG) and serum triglyceride (TG) levels, improving glucose tolerance and insulin sensitivity, and activating the peroxisome proliferator-activated receptor (PPAR) signaling pathway. 75 Accumulating evidence has demonstrated that flavonoids derived from P. odoratum possess considerable hypoglycemic activity. For instance, total flavonoids (50–200 mg/kg) dose-dependently lowered FBG in STZ-induced type 1 diabetic mice and alloxan-induced type 2 diabetic rats. At 200 mg/kg, the flavonoids demonstrated efficacy comparable to acarbose (20 mg/kg) and gliclazide (15 mg/kg), whereas lower doses were less effective. Mechanistically, these antihyperglycemic effects likely involve enhanced insulin secretion and α-amylase inhibition. 76 Three isoflavone compounds ( 86, 89 , and 90 ) from the ethanol extract of P. odoratum inhibited AGE formation with IC 50 values of 107.10, 56.30 and 46.05 μM, respectively. 35 Compounds 91, 92, and 110 were confirmed to act as insulin sensitizers, increasing insulin-stimulated glucose uptake in 3T3-L1 cells and ameliorating insulin resistance. 34 Homoisoflavanone from P. odoratum , including compounds 99, 100, 101 , and 116 , have been reported to activate adenosine 5′-monophosphate-activated protein kinase (AMPK). 43 In the Caco-2 cells, sappanin-type homoisoflavonoids ( 89, 90 , and 98 ) inhibited glucose transporter 2 (GLUT2)-mediated glucose transport by 50.5 ± 7.6%, 47.5 ± 1.9%, and 41.6 ± 2.5%, under a glucose concentration of 25 mmol/L, with their inhibitory effects overall being stronger than common flavonoids. Furthermore, these compounds showed synergistic effects with sodium-glucose cotransporter 1 (SGLT1) inhibitors, further suppressing intestinal glucose transport, suggesting that homoisoflavonoids may represent an important material basis for the hypoglycemic effects of P. odoratum . 77 Additionally, polyhydroxylated alkaloids from P. odoratum , 1-deoxynojirimycin ( 142 ) and fagomine ( 143 ), exhibited significant anti-α-glucosidase activity with IC 50 values of 0.098 and 0.272 mol/mL, respectively, with results superior to those of the positive control, acarbose. 49 Table 3 Pharmacological Activities of P. odoratum Test Samples Extraction Solvent Experimental Model Regulatory Mechanism References Amelioration of diabetes and its complications Rhizome extracts Water In vivo: HFD/STZ-induced diabetic mice, alloxan-induced diabetic mice Blood glucose↓, TC↓, TG↓ [ 71 ] Rhizome extracts 30% ethanol In vivo: STZ-induced diabetic mice CD4 + /CD8 + ↓, IFN-γ↓, IL-4↑, IL-10↑ [ 72 ] Rhizome extracts Ethanol In vivo: STZ-induced diabetic mice AGEs↓ [ 73 ] Rhizome extracts 30% ethanol In vivo: STZ-induced diabetic mice IFN-γ↓, IFN-γ/IL-4↓ [ 74 ] Rhizome extracts 75% ethanol In vivo: HFD-induced C57BL/6 mice In vitro: HepG2 cells In vivo: FBG↓, TG↓, TC↓, TNF-α↓, In vivo and in vitro: UCP-2↑, PPARα↑, PPARγ↑, PGC-1β↑, LPL↑, ACO↑, Glut4↑ [ 75 ] Rhizome extracts 70% ethanol In vivo: STZ and alloxan-induced diabetic rats In vitro: α-amylase inhibition assay In vivo: FBG↓, INS↑ In vitro: α-amylase↓ [ 76 ] Ophiopogonanone E ( 91 ) 90% methanol In vitro: insulin-stimulated 3T3-L1 adipocytes Glucose uptake↑ [ 34 ] (±)-5,7-Dihydroxy-6,8-dimethyl-3-(2’-hydroxy-4’-methoxybenzyl)chroman-4-one ( 92 ) 5,7-Dihydroxy-6,8-dimethyl-3( R, S )-(3′-hydroxy-4′-methoxybenzyl)chroman-4-one ( 110 ) Odoratumone A ( 86 ) 95% ethanol In vivo: STZ-induced diabetic rats In vitro: BSA-glucose assay In vivo and in vitro: AGEs↓ [ 35 ] 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4′-hydroxybenzyl)chroman-4-one ( 89 ) 5,7-Dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)chroman-4-one ( 90 ) ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-6,8-dimethylchroman-4-one ( 99 ) 70% ethanol In vitro: 3T3-L1 adipocytes AMPK↑ [ 43 ] ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-8-methoxy-6-methylchroman-4-one ( 100 ) ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-6-methylchroman-4-one ( 101 ) Polygonatone D ( 116 ) 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4′-hydroxybenzyl)chroman-4-one ( 89 ) 70% and 95% ethanol In vitro: Caco-2 cells Inhibit GLUT2-mediated glucose transport [ 77 ] 5,7-Dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)chroman-4-one ( 90 ) 5,7,4′-Trihydroxy-6-methyl-dihydrohomoisoflavone ( 98 ) 1-Deoxynojirimycin ( 142 ) Water In vitro: p-Nitrophenyl-α-D-glucopyranoside method α-glucosidase↓ [ 49 ] Fagomine ( 143 ) POPs Water In vivo: STZ-induced diabetic mice TG↓, IFN-γ↓, IL-4↑, IL-10↑, INS↑ [ 78 ] POPs Water In vivo: HFD/STZ-induced diabetic mice FBG↓, HbAlc↓, TG↓, TC↓, LDL-C↓, MDA↓, p-JNK↓, NF-κB p65↓, FINS↑, C-peptide↑, SOD↑ [ 79 ] POPs N/A In vitro: oleic acid-induced HepG2 cells TG↓, TC↓, ROS↓, NF-κB↓, TLR4↓, SOD↑ [ 80 ] POPs N/A In vivo: STZ-induced diabetic mice MDA↓, ALT↓, AST↓, TC↓, TG↓, HDL-C↓, LDL-C↓, CREA↓, BUN↓, p-JNK↓, SOD↑, CAT↑, GSH-Px↑, IRS-2↑, PI3K p85↑, NF-κB p65↓, Nrf2↑, HO-1↑ [ 81 ] POPs Water In vivo: HFD/STZ-induced diabetic mice In vitro: HuTu-80 cells In vivo: FBG↓, AUC↓, TG↓, TC↓, LDL-C↓, INS↑, HDL-C↑ in vitro: TRPM5 mRNA↑, cAMP↑, GLP-1↑, T1R2/T1R3 mRNA↑ [ 82 ] POP1 Water In vivo: STZ-induced diabetic mice Regulate PI3K-AKT-GSK3β/FoxO1 signaling pathway [ 64 ] P. odoratum protein hydrolysate (POP) N/A In vivo: HFD/STZ-induced diabetic mice Regulate the Nrf2/HO-1 signaling pathway, ROS↓, MDA↓, SOD↑, GSH-Px↑, HO-1↑ [ 83 ] Enhancement of immune functions and anti-inflammatory effects Rhizome extracts Water In vitro: Con A-induced mouse splenic lymphocytes IL-2↓ [ 84 ] Rhizome extracts N/A In vivo: Polycystic Ovary Syndrome rats IL-1β↓, TNF-α↓, NO↓ [ 85 ] Rhizome extracts 30% ethanol In vitro: LPS activation of murine peritoneal macrophages IL-6↓, TNF-α↓, NO↓ [ 86 ] Rhizome extracts 30% ethanol In vitro: LPS activation of murine peritoneal macrophages iNOS↓, NO↓ [ 87 ] Total saponins from the n -BuOH fraction Methanol In vitro: Con A-induced mouse splenocyte proliferation assay Promote the proliferation of mouse spleen cells [ 23 ] 26- O-β-D -glucopyranosyl-22- O -methyl-(25 S )-Furost-5-ene-3 β ,26-diol-3- O-β -D-glucopyranosyl(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl(1→4) β -D galactopyranoside ( 11 ) 26- O-β -D-glucopyranosyl-(25 R,S )-Furost-5-ene-3 β ,14 α ,22α,26-quarol-3- O-β -D-glucopyranosyl(1→2)-[ β-D -xylopyranosyl-(1→3)]-β-D-glucopyranosyl(1→ 4) β -D galactopyranoside ( 15 ) Zizybeoside I ( 152 ) Enzyme-treated extract (ETP) N/A In vivo: CTX-induced hepatointestinal injury mouse model IL-2↑, IL-22↑, SOD↑, IL-6↓, IL-17↓, IFN-γ↓, regulate JAK/STAT3-related inflammatory signaling [ 88 ] P. odoratum oligosaccharides (POs) Water In vivo: DSS-induced colitis mouse model In vitro: Caco-2 cells In vivo: SCFAs↑ In vitro: IL-1β↓, IL-8↓ [ 89 ] POPs 30% ethanol In vivo: D-gal-induced aging model mice CD8 + T cells↑, CD4 + /CD8 + ↓ [ 90 ] POPs 30% ethanol In vitro: ConA-induced ex vivo splenocyte proliferation model CD4 + αβT/CD8 + αβT↓, IFN-γ↑ [ 91 ] POPs Water In vitro: ethanol-treated HepG2 cells ALT↓, AST↓, ROS↓, MDA↓, IL-1β↓, TNF-α↓, Keap1↓, GSH↑, p-Nrf2↑, NQO1↑ [ 92 ] Antioxidant and anti-aging effects Rhizome extracts Distilled water In vivo: D-gal-induced aging model mice In vitro: DPPH radical scavenging assay In vivo: MDA↓, SOD↑ In vitro: DPPH·↓ [ 93 ] Rhizome extracts Water and ethanol In vitro: DPPH radical scavenging assay, ABTS radical scavenging assay In vitro: DPPH·↓, ABTS + ↓ [ 94 ] Rhizome extracts (total flavonoids) 80% ethanol In vitro: DPPH radical scavenging assay In vitro: DPPH·↓ [ 38 ] Rhizome extracts (total flavonoids) 40% ethanol In vitro: DPPH radical scavenging assay, Hydroxyl radical scavenging assay, Superoxide anion radical scavenging assay, ABTS radical scavenging assay, Nitrite scavenging assay DPPH·↓, ·OH↓, ·O 2 − ↓, NaNO 2 ↓, ABTS + ↓ [ 95 ] 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4′-hydroxybenzyl)chroman-4-one ( 89 ) N/A In vitro: DPPH radical scavenging assay DPPH·↓ [ 41 ] 5,7,4′-Trihydroxy-6-methyl-dihydrohomoisoflavone ( 98 ) (3 R )-5,7-Dihydroxy-8-methyl-3-(2′,4′-dihydroxybenzyl)-chroman-4-one ( 102 ) 75% ethanol In vitro: DPPH radical scavenging assay DPPH·↓ [ 42 ] (3 R )-5,7-Dihydroxy-3-(2’,4’-dihydroxyben-zyl)-chroman-4-one ( 105 ) (3 R )-5,7-Dihydroxy-6-methoxy-8-methyl-3-(2’,4’-dihydro-xybenzyl)-chroman-4-one ( 109 ) Odoratumone A ( 86 ) Choline chloride: ethylene glycol=1:1 In vivo: zebrafish embryo In vitro: DPPH radical scavenging assay, Hydroxyl radical scavenging assay In vivo: ROS↓, MDA↓, SOD↑ In vitro: DPPH·↓, ·OH↓, [ 32 ] 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4’-hydroxybenzyl)chroman-4-one ( 89 ) 5,7-Dihydroxy-6,8-dimethyl-3-(4’-hydroxybenzyl)chroman-4-one ( 90 ) (±)-5,7-Dihydroxy-6,8-dimethyl-3-(2′-hydroxy-4′-methoxybenzyl)chroman-4-one ( 92 ) 5,7,4’-Trihydroxy-6-methyl-dihydrohomoisoflavone ( 98 ) POPs Water In vivo: D-gal-induced aging model mice SOD↑, T-AOC↑, MDA↓, Caspase-3↓, IL-1β↓, IL-6↓, TNF-α↓ [ 39 ] WPOP-A-c water In vitro: HepG2 cells, DPPH radical scavenging assay, ABTS radical scavenging assay SOD↑, MDA↓, DPPH·↓, ABTS + ↓ [ 96 ] Antitumor activity Rhizome extracts Methanol In vitro: MDA-MB-231 cells ΔΨm↓, Bcl-2↓, Bax↑ [ 97 ] Rhizome extracts 70% ethanol In vitro: BGC-823, SGC-7901 Regulating the epithelial–mesenchymal transition process [ 98 ] Rhizome extracts 30% ethanol In vivo: s-180 tumor-bearing mouse In vitro: CL-187 cells In vivo: IL-2↑, IL-1↑, TNF-α↑ in vitro: inhibit the proliferation of CL-187 cells [ 99 ] 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4’-hydroxybenzyl)chroman-4-one ( 89 ) 95%ethanol In vitro: A549 cells p-p38↑, p53↑, caspase-3↑, p-Cdc2↑, Cdc2↓ [ 100 ] 5,7-Dihydroxy-6,8-dimethyl-3-(4’-hydroxybenzyl)chroman-4-one ( 90 ) Methanol In vitro: T47D and MCF-7 cells p21↑, p53↑ [ 37 ] P. odoratum lectin (POL) 0.9% NaCl solution In vitro: MCF-7 cells Inhibits the EGFR-mediated Ras-Raf-MEK-ERK signaling pathway [ 101 ] POL NaAc-HAc buffer In vitro: HSV-II-infected vero cells, A375 cells Inhibit the proliferation of HSV-II and A375 cells [ 102 ] POL NaAc-HAc buffer In vitro: 30 paired samples of primary malignant melanoma tissues and adjacent normal tissues from melanoma patients miR1290↓, BECN1 ↑ [ 103 ] POL 0.9% NaCl solution In vitro: A549 cells p-AKT↓, p-NF-κB↓, p-mTOR↓ [ 104 ] POPs Water In vivo: Sarcoma 180 and Ehrlich ascites carcinoma mouse models Inhibited tumor growth [ 105 ] POPs N/A In vitro: A549 cells Wnt3a↓, β-catenin↓, CyclinD1↓ [ 106 ] Antimicrobial and antiviral activity (25 S )-Spirosta-5-ene-3 β ,12 β -diol 3- O -{ β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)}- β -D-galactopyranoside ( 52 ) 70% ethanol In vitro : Candida albicans JCM1542, Aspergillus fumigatus JCM1738 N/A [ 18 ] (25 S )-Spirosta-5,14-dien-3 β -ol 3- O -{ β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)]- β -D-glucopyranosyl-(1→4)}- β -D-galactopyranoside ( 79 ) 70% ethanol In vitro: Candida albicans JCM1542, Aspergillus fumigatus JCM1738 N/A [ 18 ] 3- O-β -D-glucopyranosyl-(1→2)-[ β -D-xylopyranosyl-(1→3)] -β -D-glucopyran-osyl-(1→4)-galactopyranosy1-25( S )-Spirost-5(6)-en-3 β -ol ( 56 ) 70% ethanol In vitro: Candida albicans JCM1542, Aspergillus fumigatus JCM1738 MIC: Candida albicans JCM1542: 3.1 µg/mL Aspergillus fumigatus JCM1738: 6.3 µg/mL [ 18 ] Odoratumone A ( 86 ) Ethanol In vitro: Escherichia coli, Bacillus cereus, Serratia marcescens, Clavibacter michiganensis subsp. sepedonicus Zone of inhibition↑ [ 31 ] 5,7-Dihydroxy-6-methyl-8-methoxy-3-(4’-hydroxybenzyl)chroman-4-one ( 89 ) Polygodoraside G (21) 70% ethanol In vitro: 293T-Gluc cells Antiviral: IC 50 = 14.30 µM [ 48 ] ( R )-5,7-Dihydroxy-3-(4-hydroxybenzyl)-8-methoxy-6-methylchroman-4-one ( 100 ) 70% ethanol In vitro: 293T-Gluc cells Antiviral: IC 50 = 49.70 µM [ 48 ] Emodin ( 154 ) 70% ethanol In vitro: 293-T cells Anti-influenza A: IC 50 = 11.0 µM [ 26 ] Physcion ( 155 ) 70% ethanol In vitro: 293-T cells Anti-influenza A: IC 50 = 2.3 µM [ 26 ] Polygodoquinone A ( 156 ) 70% ethanol In vitro: 293-T cells Anti-influenza A: IC 50 = 11.4 µM [ 26 ] Cardioprotective effects Rhizome extracts Water In vitro: cardiomyocytes with oxygen-glucose deprivation-induced injury Spontaneous beating rate↓, lactate dehydrogenase↓ [ 107 ] Rhizome extracts 70% ethanol In vivo: myocardial ischemia-reperfusion injury rat model FFA↓, LAC↓, caspase-3↓, caspase-6↓, caspase-9↓, MDA↓, LVDP↓, -dp/dtmax↓, ATP/AMP↑, SOD↑, LVSP↑, +dp/dtmax↑ [ 108 ] Rhizome extracts 30% ethanol In vitro: mouse peripheral blood monocytes TXB 2 ↓ [ 109 ] Rhizome extracts 70% ethanol In vivo: in rats of heart failure following myocardial infarction HR↓, LVSP↓, +dp/dtmax↓, -dp/dtmax↓, LVDP↑ [ 110 ] Anti-obesity effects POPs 95% ethanol In vivo: HFD-induced diabetic mice Lee′s index and the fat coefficient↓, TG↓, TC↓, LDL-C↓ [ 111 ] POPs Water In vivo: HFD-induced obese rats TG↓, TC↓, LDL-C↓, p-NF-κB p65↓, MDA↓, TNF-α↓, IL-6↓ [ 112 ] POPs N/A In vivo: HFD-induced obese rats Gut microbiota modulation, SCFAs↓, TC↓, TG↓, Fas↓, Srebf1 ↓, Fabp4↓, Ppara ↑, Pparg↑, Atgl ↑ [ 113 ] Other effects Rhizome extracts N/A In vivo: cyclophosphamide-induced micronucleus mouse Micronucleus frequency↓ [ 114 ] Rhizome extracts 80% ethanol In vitro: tyrosinase dopachrome method Biphasic regulation of tyrosinase activity [ 115 ] Rhizome extracts 80% ethanol In vitro: tyrosinase dopachrome method Activate tyrosinase [ 116 ] Rhizome extracts Water In vivo: Weight-loaded swimming test in mice Anti-fatigue effect [ 117 ] Rhizome extracts Water In vivo: a weight loaded swimming model and a free-swimming model of mice SOD↑, CAT↑, GSH↑, LDH↓, BUN↓, MDA↓ [ 118 ] Rhizome extracts Water In vitro: eutopic endometrial cells from women with endometriosis IL-6↓, CA-125↓ [ 119 ] Rhizome extracts 30% ethanol In vitro: RAW 264.7 cells NFATc1↓, c-Fos↓, TRAP↓, OSCAR↓, MMP-9↓ [ 120 ] Rhizome extracts N/A In vitro: BV2 cells TNF-α↓, STAT3↑ [ 121 ] N-trans-p -coumaroyltyramine ( 139 ) N/A In vitro: BEAS-2B cells EGFR↓, HIF1A↓, GSK3β↓ [ 122 ] Notes : N/A = data not available. ↓: molecular-level decrease. ↑: molecular-level increase. →: glycosidic linkage direction (non-reducing → reducing end). Abbreviations : HFD, High-Fat Diet; STZ, Streptozotocin; TC, Total Cholesterol; TG, Triglyceride; AGEs, Advanced Glycation End-products; FBG, Fasting Blood Glucose; TNF-α, Tumor Necrosis Factor-α; PPAR, Peroxisome Proliferator-Activated Receptor; UCP-2, Uncoupling Protein 2; LPL, Lipoprotein Lipase; ACC, Acetyl-CoA Carboxylase; ACO, Acyl-CoA Oxidase; Glut4, Glucose Transporter Type 4; INS, Insulin; AMPK, AMP-Activated Protein Kinase; GLUT2, Glucose Transporter Type 2; SGLT1, Sodium-Glucose Linked Transporter 1; HbAlc, Glycated Hemoglobin; LDL-C, Low-Density Lipoprotein Cholesterol; MDA, Malondialdehyde; JNK, c-Jun N-Terminal Kinase; NF-κB, Nuclear Factor-κB; SOD, Superoxide Dismutase; FINS, Fasting Insulin; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; HDL-C, High-Density Lipoprotein Cholesterol; CREA, Creatinine; BUN, Blood Urea Nitrogen; CAT, Catalase; GSH-Px, Glutathione Peroxidase; IRS-2, Insulin Receptor Substrate-2; PI3K, Phosphoinositide 3-Kinase; Nrf2, Nuclear Factor Erythroid 2-Related Factor 2; HO-1, Heme Oxygenase-1; AUC, Area Under the Curve; GLP-1, Glucagon-Like Peptide-1; cAMP, Cyclic Adenosine Monophosphate; T1R2/T1R3, Taste Receptor Type 1 Member 2/3; TRPM5, Transient Receptor Potential Cation Channel Subfamily M Member 5; GSK3β, Glycogen Synthase Kinase-3β; FoxO1, Forkhead Box O1; Con A, Concanavalin A; IL, Interleukin; IFN-γ, Interferon-γ; LPS, Lipopolysaccharide; iNOS, Inducible Nitric Oxide Synthase; CTX, Cyclophosphamide; JAK/STAT3, Janus Kinase/Signal Transducer and Activator of Transcription 3; DSS, Dextran Sulfate Sodium; SCFAs, Short-Chain Fatty Acids; D-gal, D-Galactose; Bcl-2, B-cell Lymphoma-2; Bax, Bcl-2-Associated X Protein; Keap1, Kelch-like ECH-Associated Protein 1; NQO1, NAD(P)H:Quinone Oxidoreductase 1; ROS, Reactive Oxygen Species; T-AOC, Total Antioxidant Capacity; Cdc2, Cell division cycle 2; Caspase, Cysteinyl-aspartate protease; ΔΨm, Mitochondrial Membrane Potential; EGFR, Epidermal Growth Factor Receptor; mTOR, Mammalian Target of Rapamycin; HSV-II, Herpes Simplex Virus Type II; MIC, Minimum Inhibitory Concentration; LVDP, Left Ventricular Developed Pressure; LVSP, Left Ventricular Systolic Pressure; ±dp/dtmax, Maximum Rate of Left Ventricular Pressure Rise/Decline; FFA, Free Fatty Acids; LAC, Lactic Acid; ATP/AMP, Adenosine Triphosphate/Adenosine Monophosphate; TXB 2 , Thromboxane B 2 ; HR, Heart Rate; Fas, Fatty Acid Synthase; Srebf1, Sterol Regulatory Element-Binding Transcription Factor 1; Fabp4, Fatty Acid Binding Protein 4; Atgl, Adipose Triglyceride Lipase; CA-125, Cancer Antigen 125; NFATc1, Nuclear Factor of Activated T-cells, Cytoplasmic 1; c-Fos, cellular Fos proto-oncogene; TRAP, Tartrate-Resistant Acid Phosphatase; OSCAR, Osteoclast-Associated Receptor; MMP-9, Matrix Metalloproteinase-9; BECN1 , Beclin-1. Pharmacological Activities of P. odoratum Notes : N/A = data not available. ↓: molecular-level decrease. ↑: molecular-level increase. →: glycosidic linkage direction (non-reducing → reducing end). Abbreviations : HFD, High-Fat Diet; STZ, Streptozotocin; TC, Total Cholesterol; TG, Triglyceride; AGEs, Advanced Glycation End-products; FBG, Fasting Blood Glucose; TNF-α, Tumor Necrosis Factor-α; PPAR, Peroxisome Proliferator-Activated Receptor; UCP-2, Uncoupling Protein 2; LPL, Lipoprotein Lipase; ACC, Acetyl-CoA Carboxylase; ACO, Acyl-CoA Oxidase; Glut4, Glucose Transporter Type 4; INS, Insulin; AMPK, AMP-Activated Protein Kinase; GLUT2, Glucose Transporter Type 2; SGLT1, Sodium-Glucose Linked Transporter 1; HbAlc, Glycated Hemoglobin; LDL-C, Low-Density Lipoprotein Cholesterol; MDA, Malondialdehyde; JNK, c-Jun N-Terminal Kinase; NF-κB, Nuclear Factor-κB; SOD, Superoxide Dismutase; FINS, Fasting Insulin; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; HDL-C, High-Density Lipoprotein Cholesterol; CREA, Creatinine; BUN, Blood Urea Nitrogen; CAT, Catalase; GSH-Px, Glutathione Peroxidase; IRS-2, Insulin Receptor Substrate-2; PI3K, Phosphoinositide 3-Kinase; Nrf2, Nuclear Factor Erythroid 2-Related Factor 2; HO-1, Heme Oxygenase-1; AUC, Area Under the Curve; GLP-1, Glucagon-Like Peptide-1; cAMP, Cyclic Adenosine Monophosphate; T1R2/T1R3, Taste Receptor Type 1 Member 2/3; TRPM5, Transient Receptor Potential Cation Channel Subfamily M Member 5; GSK3β, Glycogen Synthase Kinase-3β; FoxO1, Forkhead Box O1; Con A, Concanavalin A; IL, Interleukin; IFN-γ, Interferon-γ; LPS, Lipopolysaccharide; iNOS, Inducible Nitric Oxide Synthase; CTX, Cyclophosphamide; JAK/STAT3, Janus Kinase/Signal Transducer and Activator of Transcription 3; DSS, Dextran Sulfate Sodium; SCFAs, Short-Chain Fatty Acids; D-gal, D-Galactose; Bcl-2, B-cell Lymphoma-2; Bax, Bcl-2-Associated X Protein; Keap1, Kelch-like ECH-Associated Protein 1; NQO1, NAD(P)H:Quinone Oxidoreductase 1; ROS, Reactive Oxygen Species; T-AOC, Total Antioxidant Capacity; Cdc2, Cell division cycle 2; Caspase, Cysteinyl-aspartate protease; ΔΨm, Mitochondrial Membrane Potential; EGFR, Epidermal Growth Factor Receptor; mTOR, Mammalian Target of Rapamycin; HSV-II, Herpes Simplex Virus Type II; MIC, Minimum Inhibitory Concentration; LVDP, Left Ventricular Developed Pressure; LVSP, Left Ventricular Systolic Pressure; ±dp/dtmax, Maximum Rate of Left Ventricular Pressure Rise/Decline; FFA, Free Fatty Acids; LAC, Lactic Acid; ATP/AMP, Adenosine Triphosphate/Adenosine Monophosphate; TXB 2 , Thromboxane B 2 ; HR, Heart Rate; Fas, Fatty Acid Synthase; Srebf1, Sterol Regulatory Element-Binding Transcription Factor 1; Fabp4, Fatty Acid Binding Protein 4; Atgl, Adipose Triglyceride Lipase; CA-125, Cancer Antigen 125; NFATc1, Nuclear Factor of Activated T-cells, Cytoplasmic 1; c-Fos, cellular Fos proto-oncogene; TRAP, Tartrate-Resistant Acid Phosphatase; OSCAR, Osteoclast-Associated Receptor; MMP-9, Matrix Metalloproteinase-9; BECN1 , Beclin-1. POPs significantly lower blood sugar levels and regulate metabolism. POPs lowered blood glucose levels, reduced interferon (IFN)-γ levels, increased interleukin (IL)-4 and IL-10 levels, and improved glucose metabolism disorders in STZ-induced diabetic mice. 78 POPs ameliorated glucose and lipid metabolic disorders in rats with type 2 diabetes induced by HFD/STZ, significantly reducing FBG, glycated hemoglobin (HbAlc), TG, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing fasting insulin, C-peptide levels, and superoxide dismutase (SOD) activity. In addition, they decreased malondialdehyde (MDA) content, inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor kappa-B (NF-κB) p65 protein, and attenuated inflammatory responses and pancreatic β -cell damage. 79 POPs were shown to ameliorate lipid metabolism disorders and liver pathology through alleviate oxidative stress and hepatic lipid accumulation by inhibiting the NF-κB pathway, 80 regulate glucose metabolism and mitigate oxidative damage via the phosphatidylinositol 3-kinase/protein kinase B-nuclear factor erythroid 2-related factor 2 (PI3K/AKT-Nrf2) signaling pathway, 81 and activate the intestinal sweet taste receptor signaling pathway, which promotes the mRNA expression of T1R2/T1R3 , and TRPM5 , stimulating glucagon-like peptide-1 (GLP-1) secretion to regulate blood glucose. 82 Moreover, a structurally distinct neutral polysaccharide (POP1) isolated from P. odoratum was shown to improve hyperglycemia in diabetic mice, potentially through modulation of the PI3K-AKT-glycogen synthase kinase 3 beta (GSK3β)/forkhead box protein O1 (FoxO1) signaling pathway. 64 Recent evidence also indicates that protein-derived peptides may contribute to the antidiabetic activity of P. odoratum. P. odoratum protein hydrolysate (POP) consisted predominantly of peptides below 1.5 kDa (approximately 90%), mainly 4–9 amino acids in length. POP (171, 684 mg/kg/day) improved hyperglycemia, glucose tolerance, insulin sensitivity, and lipid metabolism in HFD/STZ-induced diabetic mice, while enhancing antioxidant capacity and Nrf2/heme oxygenase-1 (HO-1) signaling, suggesting that bioactive peptides may represent an additional material basis for the glucose-regulating effects of P. odoratum . 83 In summary, P. odoratum has been reported to exert synergistic hypoglycemic effects in preclinical models through multi-component, multi-target, and multi-pathway mechanisms. Its active constituents can enhance insulin sensitivity, inhibit α-glucosidase activity and intestinal glucose transport, and activate the AMPK signaling pathway, thereby lowering blood glucose levels, regulating metabolism, and alleviating inflammation and oxidative stress. However, these findings are currently confined to preclinical models, and the definitive efficacy and safety in humans require rigorous clinical validation. Future research should be pursued along the following three distinct directions: clinical trials to evaluate the efficacy and safety of standardized P. odoratum preparations in humans, structure–activity relationship (SAR) studies on isolated constituents through comparative testing of analogues in controlled in vitro systems to identify the key pharmacophores responsible for the hypoglycemic activity, andmechanistic investigations utilizing combination-index analysis, network pharmacology, and molecular approaches to validate the proposed multi-target synergistic actions. The traditional effects of P. odoratum in “replenishing deficiency, reinforcing healthy qi , and benefiting qi ” correspond primarily to its modern pharmacological activities, namely immunopotentiation and anti-inflammatory modulation. P. odoratum extracts significantly inhibited IL-2 production in mouse spleen lymphocytes induced by concanavalin A (Con A), 84 and downregulated the expression of the inflammatory cytokines, tumor necrosis factor (TNF)-α and IL-1β, in the ovaries of a rat model of polycystic ovary syndrome. 85 In addition, an ethanol-water extract of P. odoratum markedly inhibits IL-6, TNF-α, and nitric oxide (NO) secretion in lipopolysaccharide (LPS)-induced macrophages. 86 These immunomodulatory effects were achieved by downregulating inducible nitric oxide synthase (iNOS) expression, which in turn inhibits NO secretion. 87 Further investigation revealed that the total saponins from the n -BuOH extract of P. odoratum obtained by methanol extraction, along with saponins 11, 15 , and 152 , promoted splenocyte proliferation and enhanced cellular immune function in mice. 23 Multi-omics analysis showed that enzymatic treatment enhanced the hepatointestinal protective and immunomodulatory effects of P. odoratum extract. In a cyclophosphamide (CTX)-induced mouse model, the enzyme-treated extract (ETP, 200 mg/kg/day) exhibited greater protective effects than the conventional water extract, reducing serum IL-6, IL-17, and IFN-γ levels, increasing IL-2 and IL-22 levels, and improving intestinal barrier damage and Treg/Th17 immune imbalance. ETP also enhanced hepatic SOD activity and modulated JAK/STAT3-related inflammatory signaling. Furthermore, gut microbiota and metabolomic analyses showed that ETP partially reversed CTX-induced microbial dysbiosis and affected purine, fructose, and bile acid metabolism. 88 P. odoratum oligosaccharides (POs) exerted protective effects on the intestine in a dextran sulfate sodium (DSS)-induced colitis mouse model. POs were prepared by hydrolyzing P. odoratum polysaccharides and had an average molecular weight of 2.42 kDa. In vitro, POs (25–200 μg/mL) dose-dependently inhibited TNF-α-induced secretion of IL-1β and IL-8 in Caco-2 cells. In DSS-induced colitis mice, POs (100 and 400 mg/kg) reduced the disease activity index, alleviated colonic pathological injury, restored intestinal barrier function, and increased the levels of short-chain fatty acids (SCFAs) in the cecum and colon. 89 In a D–galactose–induced aging mouse model, 50 Kunming mice treated with POPs (0.5, 1, and 2 g/kg) for 6 weeks showed improved immune function and delayed aging. All doses increased thymus and spleen indices, enhanced T and B lymphocyte proliferation, upregulated CD8 + T‑cell numbers, lowered the CD4 + /CD8 + ratio, and boosted both cellular and humoral immunity. 90 In a mouse splenic lymphocyte system, POPs also promote mouse spleen αβT cell proliferation, decrease the CD4 + αβT to CD8 + αβT cell ratio, increase the number of CD8 + αβT cells, and stimulate IFN-γ release from mouse splenic lymphocytes, thereby strengthening cellular immune function in mice. 91 POPs alleviated alcohol-induced oxidative stress, inflammation, and apoptosis in HepG2 cells by activating the Nrf2/Keap1 signaling pathway, upregulating NAD(P)H:quinone oxidoreductase 1 (NQO1) expression, increasing glutathione (GSH) levels, and reducing the levels of reactive oxygen species (ROS), MDA, and the inflammatory cytokines IL-1β and TNF-α ( Figure 11 ). 92 Figure 11 Molecular mechanism of P. odoratum for immunoenhancement and anti-inflammation. The diagram illustrates the molecular mechanism of Polygonatum odoratum rhizome extracts for immunoenhancement and anti-inflammation. The rhizome extracts, including POPs, POP and POP1, enter the cell membrane. On the left, inducible nitric oxide synthase is inhibited, reducing nitric oxide production, leading to anti-inflammatory effects. This affects cytokines such as interleukin 1 beta, interleukin 6, interleukin 2 and tumor necrosis factor alpha. On the right, active compounds activate Nrf2 by inhibiting Keap1, leading to immunopotentiation of CD4 plus/CD8 plus cells. Nrf2 activation results in antioxidative effects by increasing NAD(P)H:quinone oxidoreductase 1 and glutathione levels, reducing reactive oxygen species and malondialdehyde. Nrf2 also translocates to the nucleus, where it binds with sMaf to antioxidant response elements, promoting interferon gamma production. Polygonatum odoratum rhizome boosts immunity, reduces inflammation via iNOS, Nrf2, Keap1 pathways. Molecular mechanism of P. odoratum for immunoenhancement and anti-inflammation. P. odoratum exerts immunoenhancing and anti-inflammatory effects by regulating lymphocyte proliferation, cytokine secretion, and signaling pathways. Current research has largely focused on the holistic effects of crude extracts, with limited investigation into the specific targets and pathways of the individual active components. Therefore, future efforts should prioritize the discovery of bioactive constituents of P. odoratum and explore their underlying molecular targets. In recent years, TCM has become increasingly significant in anti-aging and antioxidant research, owing to its unique therapeutic effects. Shen Nong Ben Cao Jing notes that P. odoratum can “lighten the body and prevent aging”. P. odoratum has been widely used by physicians throughout history to treat various age-related diseases. 93 Modern studies on the antioxidant and anti-aging effects of P. odoratum have garnered considerable attention from the research community. The water extract of P. odoratum has been confirmed to contain anti-aging active components, as evidenced by its ability to prevent thymus and spleen atrophy and ameliorate pathological damage in aged mice, thereby providing evidence for its antioxidant efficacy. 93 Further investigation into processing methods revealed that different steaming procedures increased total phenols by 6.21–8.35-fold and total saponins by 1.84–2.34-fold. DPPH and ABTS radical scavenging rates were enhanced by 1.87–2.49-fold and 1.11–2.18-fold. These results indicate that steaming effectively augments its antioxidant potential. 94 With regard to the active fractions, total flavonoids from P. odoratum showed high antioxidant capacity by scavenging DPPH in vitro. 38 Their DPPH scavenging capacity was enhanced after forming complexes with iron. 123 Furthermore, the ·OH, ·O 2‒ , NaNO 2 , and ABTS + scavenging abilities and reducing power of the total flavonoids were superior to those of the vitamin C (V C ) solution, and the scavenging rates of various free radicals and nitrites increased in a concentration-dependent manner. 95 Various compounds isolated from P. odoratum exhibit significant antioxidant activity. In addition, five dihydrohomoisoflavones ( 86, 89, 90, 92 , and 98 ) extracted from P. odoratum exhibited antioxidant effects. Notably, compound 98 had stronger antioxidant activity than V C at equivalent concentrations. 32 Two C-methylated homoisoflavones ( 89 and 98 ) demonstrated antioxidant capacities comparable to that of rutin. 41 Compounds 102, 105 , and 109 showed strong DPPH radical scavenging activity, with IC 50 values of 3.8 ± 0.5, 3.9 ± 0.4, and 4.9 ± 0.3 μg/mL, respectively, significantly higher antioxidant potencies than ascorbic acid. 42 Collectively, these findings suggested that homoisoflavonoids have considerable potential as natural antioxidants. In mice, POPs improved cognitive and memory function, inhibited D-galactose-induced oxidative stress, increased SOD activity and total antioxidant capacity, reduced MDA levels, decreased inflammatory factors in hippocampal tissue, and inhibited neuronal apoptosis, thereby delaying aging and counteracting oxidative damage. 39 In addition, the pectic polysaccharide WPOP-A-c (33 kDa) isolated from P. odoratum , which comprises homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II) domains, exhibited significant in vitro antioxidant activity. Its scavenging effects against DPPH, ABTS, and hydroxyl radicals were superior to those of WLBP-A3-c from Lilium brownii , due to its higher galacturonic acid and HG domain content and lower molecular weight. Among its structural domains, HG showed the strongest activity in reducing ROS and enhancing SOD activity, effectively protecting HepG2 cells from oxidative damage. 96 P. odoratum exerts antioxidant and anti-aging effects by scavenging free radicals, increasing SOD activity, reducing MDA levels, and inhibiting oxidative stress and neuronal apoptosis. However, current studies lack in-depth investigation into the in vivo metabolism, bioavailability, and long-term safety of its active components. Future research should strengthen pharmacokinetic studies to clarify its effective forms in vivo, thereby providing a scientific basis for its development as a functional food and pharmaceutical agent. Cancer poses a serious threat to human health and survival. P. odoratum acts as a novel anticancer agent with inhibitory effects on various types of tumor cells, including breast cancer, 97 lung cancer, 100 and gastric cancer. 98 Studies indicate that the methanol extract of P. odoratum (0.02, 0.04, 0.06 mg/mL) dose-dependently downregulates B-cell lymphoma 2 (Bcl-2) levels, upregulates Bcl-2-associated X protein (Bax) levels, and reduces mitochondrial membrane potential, thereby inhibiting proliferation and inducing apoptosis in breast cancer MDA-MB-231 cells, with the highest apoptotic rate reaching 33.2%. 97 Furthermore, it effectively inhibits the proliferation and metastasis of gastric cancer cells by regulating the epithelial–mesenchymal transition process. 98 The ethanol extract exerted antitumor effects by inducing apoptosis, interfering with cell mitosis, promoting IL-2 secretion in spleen cells from tumor-bearing mice, and stimulating IL-1 and TNF-α secretion by peritoneal macrophages, thereby enhancing cellular immune function and inducing tumor cell apoptosis. In addition, the study also found that ethanol extract could inhibit the proliferation of CL-187 cells. 99 Various homoisoflavonoids from P. odoratum have been reported to inhibit tumor cell proliferation. 5,7-dihydroxy-6-methyl-8-methoxy-3-(4′-hydroxybenzyl)chroman-4-one ( 89 ) (12.5‒100 µg/mL) dose-dependently inhibited the proliferation of A549 cells, with an IC 50 of 37.11 µg/mL at 24 h. Specifically, it upregulated p-p38, p53, and p-Cell division cycle 2 (Cdc2) levels while downregulating Cdc2 levels, leading to G 2 /M phase arrest. In parallel, it activated both the mitochondrial caspase-dependent and endoplasmic reticulum stress-mediated apoptosis pathways to induce apoptosis, achieving a maximum apoptotic rate of 47.12%. 100 5,7-Dihydroxy-6,8-dimethyl-3-(4′-hydroxybenzyl)chroman-4-one ( 90 ) (50 µM) induces Bcl-2 phosphorylation and apoptosis in breast tumor cells (T47D and MCF-7 cells), causing G 2 /M cell cycle arrest and increasing p21 and p53 levels, SAR studies demonstrated that the C-8 methyl moiety is a critical structural determinant for activity, while the corresponding methoxy analogue is devoid of such biological effects. 37 P. odoratum lectin (POL) was found to induce apoptosis and autophagy in various human cancer cells, with broad antitumor potential. In human MCF-7 breast cancer cells, POL induced both apoptosis and autophagy, with mechanistic studies indicating that its apoptotic effect involved the mitochondrial pathway and, more importantly, the epidermal growth factor receptor (EGFR)-mediated rat sarcoma virus (Ras)-rapidly accelerated fibrosarcoma (Raf)-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway. Proteomic analysis further identified EGFR, Ras, Raf, MEK, and ERK as potential targets involved in POL-mediated apoptosis and autophagy, suggesting that POL may act as a potential EGFR-targeting antitumor agent. 101 Consistent with these findings, POL exhibited antitumor effects in several other cancer cell models. POL inhibited the activity of HSV-II-infected Vero cells, with an EC 50 of 5‒10 μg/mL. Its apoptosis-inducing effect on human melanoma A375 cells is dependent on the caspase pathway. 102 In A459 cells, POL downregulated miR1290, relieving its inhibition of BECN1 , which subsequently increased BECN1 expression and induced autophagy. 103 POL inhibited the Akt-NF-κB pathway and blocked the Akt-mammalian target of rapamycin (mTOR) signaling pathway in A549 cells, thereby inducing apoptosis and autophagy with an IC 50 of 23 μg/mL. Moreover, it did not induce significant apoptosis or autophagy in normal human embryonic lung fibroblasts (HELF) ( Figure 12 ). 104 Beyond lectins, POPs have also demonstrated antitumor activity in both cellular and animal models. In animal models, oral administration of POPs (20 mg/kg) significantly inhibited tumor growth in Sarcoma 180 and Ehrlich ascites carcinoma mouse models, with inhibition rates of 42% and 56%, and extended survival with life extension rates of 267% and 80%. 105 Its antitumor activity in vitro is enhanced by sulfation. 124 POPs suppress A549 cells proliferation through Wnt/β-catenin pathway inhibition, with an IC 50 of 5.927 mg/mL for standard POPs and 5.321 mg/mL for allelopathic POPs. Standard POPs downregulate Wnt3a by 67% and β-catenin by 51%, compared to 46% and 36% in the allelopathic group. Overall, the superior activity of standard POPs over allelopathic group indicates that cultivation conditions affect their efficacy, highlighting standardized cultivation as key to ensuring quality and bioactivity. 106 Figure 12 Molecular mechanism of P. odoratum for antitumor. The diagram illustrates the molecular mechanism of antitumor activity involving homoisoflavanones, rhizome extracts and polysaccharide of Polygonatum odoratum. Homoisoflavanones, rhizome extracts and polysaccharide of Polygonatum odoratum enter the cell and influence reactive oxygen species. Reactive oxygen species affect AKT, leading to the regulation of mammalian target of rapamycin and nuclear factor kappa B pathways, which induce autophagy and apoptosis. Cyclin B1 and cyclin-dependent kinase 1 are involved in G2/M phase arrest, influenced by phosphorylated p38, p53, p21 and phosphorylated cell division cycle 2. In the mitochondria, B-cell lymphoma 2 and B-cell lymphoma 2-associated X protein regulate mitochondrial membrane potential, leading to cytochrome C release. Cytochrome C activates caspase 9, caspase 3 and poly ADP ribose polymerase, promoting apoptosis. Polysaccharide of Polygonatum odoratum inhibits AKT, further affecting apoptosis pathways. Antitumor diagram: rhizome extracts, homoisoflavanones, POPs impact ROS, AKT, apoptosis pathways. Molecular mechanism of P. odoratum for antitumor. Collectively, the multiple bioactive constituents of P. odoratum have demonstrated inhibitory effects against breast, lung, and gastric cancer cell lines in both in vitro and animal models. The reported mechanisms encompass the induction of apoptosis and autophagy, cell cycle arrest, and immunomodulation. Notably, studies have observed low cytotoxicity toward normal human embryonic lung fibroblasts, suggesting a degree of selective tumor cell targeting. Nevertheless, systematic toxicity data, direct comparisons with approved anticancer agents, and comprehensive evaluations using paired cancer or normal cell lines remain unavailable. Accordingly, while P. odoratum holds promise as a source of antitumor agents, these findings should be regarded as preliminary, and further rigorous studies are warranted to fully elucidate its therapeutic potential and safety profile. In the exploration of natural products with anti-infective potential, P. odoratum has shown strong potential owing to its unique bioactive components. Steroidal saponins 52 and 79 inhibited Exserohilum turcicum and exhibited strong antibacterial activity against Bacillus cereus and Corynebacterium michiganense . The steroidal saponin 56 has shown strong antifungal potential, with a minimum inhibitory concentration (MIC) of 3.1 µg/mL against Candida albicans JCM1542 and 6.3 µg/mL against Aspergillus fumigatus JCM1738. 18 Homoisoflavonoids 86 and 89 demonstrated antimicrobial activity against specific tested strains, as indicated by enlarged zones of inhibition. 31 Compounds 21, 100, 154, 155 , and 156 exhibited inhibitory effects against the influenza A virus in vitro, with an IC 50 of 14.30, 49.70, 11.0, 2.3, 11.4 µM. Compound 155 demonstrates potent in vitro activity against influenza A virus, indicating its potential as a lead candidate for the development of antiviral therapeutics. 26 , 48 In terms of anti-infective activity, specific steroidal saponins have shown inhibitory effects against certain bacterial and fungal strains, while anthraquinone compounds have mainly demonstrated inhibitory activity against influenza A virus. These findings suggest that P. odoratum possesses certain potential in regulating gut microecology and suppressing pathogenic microorganisms. However, given that the antimicrobial spectra of different compound classes vary considerably, future studies should systematically evaluate the anti-infective activities of individual compounds using standardized panels of microbial strains. The traditional applications of P. odoratum in “nourishing yin, nourishing the heart, and unblocking the meridians” correspond to its modern pharmacological effects, including myocardial protection, improvement of cardiac function, blood pressure reduction, and anti-atherosclerotic activity. In clinical practice, Shengmai powders combined with P. odoratum and P. odoratum decoctions paired with β-blockers were used to treat heart failure. 50 Several studies have shown that P. odoratum can improve myocardial function. For instance, rat serum containing 4% P. odoratum decreased the beating frequency of myocardial cells at 30 min, and this effect stabilized after 12 h of exposure. Furthermore, rat serum containing P. odoratum at various concentrations reduced lactate dehydrogenase levels. 107 In a myocardial ischemia-reperfusion injury model established in 60 male Wistar rats, intraperitoneal administration of P. odoratum ethanol extract (100, 200, 300 mg/kg) exerted cardioprotective effects. The underlying mechanisms involved preservation of mitochondrial ultrastructure, regulation of Bcl-2/Bax and cleaved Cysteine-aspartic protease 3 (Caspase-3) to inhibit apoptosis, and reduction of ROS and MDA levels to alleviate oxidative stress. The protective effects of the 300 mg/kg extract were comparable to those of ginkgolide B (10 mg/kg), whereas the 100 mg/kg showed no significant impact on several parameters. 108 Further, P. odoratum extract inhibits endotoxin-induced thromboxane B 2 (TXB 2 ) overproduction in monocytes, albeit in a non-concentration-dependent manner, suggesting a potential interference with arachidonic acid metabolism and an anti-inflammatory or antiplatelet aggregation effect, which provides early experimental evidence for its cardiovascular protective potential. 109 Additionally, intravenous administration of the ethanol extract in rats produced significant negative inotropic and chronotropic effects on the heart, with a clear dose dependency: negative inotropy predominated at low doses, and as the dose increased, the negative inotropic effects intensified and were accompanied by a distinct negative chronotropic response. 110 Obesity is a risk factor for various metabolic diseases and is closely associated with the development of type 2 diabetes, hypertension, hyperlipidemia, and several cancers. 12 POPs (300 mg/kg) treatment produced significant positive effects on HFD-induced obesity in mice. POPs controlled the increase in body weight in mice more effectively than orlistat, reducing Lee’s index and the fat coefficient, and demonstrating strong lipid-lowering activity. They significantly reduced TC, TG, and LDL-C levels and improved glucose metabolism. 111 In another study, intragastric administration of POPs (200, 400, 600 mg/kg) for 6 weeks reduced perirenal fat mass and serum TC, TG, and LDL-C levels in obese rats. Mechanistically, this effect may be attributed to inhibition of the NF-κB signaling pathway, thus regulating immune responses, maintaining normal lipid metabolism, reducing hepatic tissue inflammation, enhancing liver function, and mitigating the toxic effects of lipid peroxidation. 112 In addition, POPs modulated gut microbiota dysbiosis by enhancing microbial richness, decreasing the relative abundance of opportunistic pathogens, and increasing short-chain fatty acids production. 113 Collectively, POPs exert anti-obesity and anti-fatty liver effects by modulating lipid metabolism pathways, inhibiting fat accumulation, improving the gut microbiota composition, and alleviating hepatic inflammation. However, the relationship between POP-induced modulation of gut microbiota and metabolic improvement remains unclear. Therefore, future studies should focus on investigating the effects of POPs on the gut microbiota. High-dose treatment with P. odoratum significantly reduced the micronucleus rate in cyclophosphamide-treated mice, demonstrating its potent antimutagenic effects. 114 P. odoratum exhibits a significant bidirectional regulatory effect on tyrosinase activity, activating it at low concentrations and inhibiting it at high concentrations. 115 At low concentrations, P. odoratum accelerates melanin synthesis by reducing the enzyme’s apparent Michaelis constant and enhancing its substrate affinity, suggesting its potential for treating vitiligo. 116 P. odoratum demonstrated significant anti-fatigue effects, potentially related to its polysaccharides and various essential amino acids. 117 POPs treatment extended exhaustive swimming time in mice, effectively inhibited exercise-induced decreases in spleen and kidney indices, delayed blood urea nitrogen generation, increased liver SOD activity, and reduced MDA levels. 118 The extract reduced IL-6 and Carbohydrate Antigen 125 (CA-125) levels in the culture supernatant of endometriosis (EE) stromal cells, reduced the production of inflammatory mediators, and blocked ectopic endometrial adhesion and growth. 119 Recent studies have further expanded the pharmacological profile of P. odoratum . An integrated network pharmacology and molecular simulation study identified 5 active constituents, 208 related targets, and 113 pruritus-associated targets, with PI3K/Akt and IL-17 signaling pathways potentially involved in the anti-pruritic effects of P. odoratum . The binding energies of the core constituent–target interactions were below −5 kcal/mol, and molecular dynamics simulations supported the stability of the complexes; however, further experimental validation is required. 125 Bone-protective activity has also been reported. In a receptor activator of NF-κB ligand (RANKL)-induced RAW 264.7 osteoclast differentiation model, the 30% ethanol extract of P. odoratum showed stronger inhibitory effects than the water extract, reducing tartrate-resistant acid phosphatase (TRAP)-positive cells and suppressing the expression of Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), cellular Fos proto-oncogene (c-Fos), TRAP, osteoclast-associated receptor (OSCAR), and matrix metalloproteinase-9 (MMP-9). These findings suggest that P. odoratum may inhibit osteoclast differentiation and bone resorption through the NFATc1/c-Fos pathway, indicating potential anti-osteoporotic activity. 120 The potential neuroprotective effects of P. odoratum have been investigated in an Alzheimer’s disease-related inflammatory model. Network pharmacology identified 8 active constituents and 172 potential targets, with PI3K/Akt and cAMP signaling pathways implicated in its potential anti-Alzheimer’s effects. In LPS-induced BV2 microglial cells, P. odoratum extract reduced TNF-α expression and increased STAT3 expression, suggesting that modulation of TNF-α-associated inflammation may contribute to its neuroprotective activity. 121 In addition, in a study integrating network pharmacology, molecular docking, molecular dynamics, and experimental validation, N-trans-p -coumaroyltyramine ( 139 ) was identified as a potential anti-fibrotic constituent. It showed strong binding to EGFR, HIF1A, and GSK3β, with binding energies of −7.7, −7.2, and −7.8 kcal/mol, and alleviated fibrotic phenotypes in a bleomycin-induced cellular fibrosis model, suggesting potential activity against idiopathic pulmonary fibrosis. 122 Overall, P. odoratum exhibits a broad pharmacological spectrum beyond its major glucose-regulating, immunomodulatory, anti-inflammatory, and antitumor effects, including antimutagenic, tyrosinase-modulating, anti-fatigue, reproductive-protective, anti-fibrotic, anti-pruritic, bone-protective, and neuroprotective activities. Nevertheless, evidence for some of these effects remains preliminary, and further in vivo studies and identification of the corresponding bioactive constituents are warranted.