Comparative Analysis of Bioactive Compounds and Health Benefits of Wild and Cultivated Ficus carica Accessions from the Northern Himalayas

Comparative Analysis of Bioactive Compounds and Health Benefits of Wild and Cultivated Ficus carica Accessions from the Northern Himalayas | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Analysis of Bioactive Compounds and Health Benefits of Wild and Cultivated Ficus carica Accessions from the Northern Himalayas Zahid Nabi Sheikh, Neha Sharma, Vikas Sharma, Parshant Bakshi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5334005/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The growing resistance to conventional antibiotics has spurred the need for alternative therapies, underscoring the significance of investigating medicinal plants for novel bioactive compounds. This study focuses on comparative qualitative and quantitative biochemical analysis, alongside an evaluation of the in vitro anti-diabetic, anti-Alzheimer, and anti-cancer properties of different wild and cultivated Ficus carica cultivars. HPLC analysis was conducted to measure the content of bioactive compounds among the wild and cultivated ficus accessions. The extracts were subsequently evaluated for their therapeutic potential against several human cancer cell lines, including prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), cervical cancer (HELA) and kidney cancer (HEK). This analysis highlighted distinct genetic similarities and differences among the ficus cultivars. Comprehensive statistical analyses were employed to discern patterns and relationships among various ficus cultivars. This research marks the first comprehensive examination of the phytochemical screening of wild and cultivated accessions of ficus ciraca . Among the cultivars examined, the wild varieties exhibited the highest concentrations of bioactive compounds and demonstrated the most significant health benefits. The results of this study provide a solid scientific basis for the future isolation and purification of therapeutic compounds in wild fruits, potentially leading to their application in pharmaceuticals or dietary supplements. This research will greatly enhance our understanding of the pharmacological properties of wild ficus fruits and establishes a basis for further investigation into their clinical benefits Antibiotics Bioactive compounds anti-diabetic anti-Alzheimer and anti-cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Research highlights Wild-02 Ganderbal exhibited the highest antioxidant activity, phenolic content, and enzyme inhibition, making it a promising candidate for pharmaceutical and dietary applications. Comparative HPLC analysis showed Wild variety leading in catechin, epicatechin, quercetin, and coumaric acid concentrations, underscoring its rich phytochemical profile. Wild-02 Ganderbal demonstrated potent anticancer activity, particularly against breast and prostate cancer cell lines, achieving up to 95% inhibition in MCF-7 cells, outperforming cultivated varieties Genetic diversity, environmental stress, and soil composition in wild cultivars contribute to their superior bioactive compound content and enhanced therapeutic properties. Introduction For centuries, humans have utilized plants for drug development, with the traditional use of natural products in disease treatment emphasizing the need to explore plants for novel therapeutic agents. The medicinal value of plants is primarily attributed to their phytochemical compounds, which exert various physiological effects on the human body (Dourado et al 2016 ; Sun and wang, 2017 ). Recently, scientific interest in the bioactivities of these natural compounds has intensified. Wild plants, in particular, tend to contain higher concentrations of bioactive compounds and exhibit stronger therapeutic properties than their cultivated counterparts. This advantage arises from their unique environmental adaptations and stress-response mechanisms. Exposure to a range of abiotic stresses, including extreme temperatures, pathogen pressure and nutrient deficiencies, drives wild plants to produce an array of secondary metabolites such as alkaloids and phenolics. These metabolites, evolved to defend against herbivores and pathogens, contribute to the plants' enhanced medicinal potential. Additionally, the evolutionary pressures in wild environments maintain high genetic diversity, leading to greater metabolite variability. In contrast, cultivated plants, selectively bred for traits like yield, size or appearance, often suffer from reduced genetic diversity, which can result in a diminished production of secondary metabolites and, consequently, lower therapeutic efficacy (Degenhardt et al., 2009; Poverenov et al., 2014 ). As a result, evaluating the biological properties of medicinal plant extracts, especially wild plants, can lead to the discovery of innovative, safe and potent bioactive compounds with anticancer, antioxidant, and antidiabetic properties (Liang et al., 2020 ; Pellegrini et al 2018 ). Bioactive compounds derived from plants are increasingly favored as natural alternatives in various sectors, such as pharmaceuticals, cosmetics, and food (Kwiatkowski et al., 2017 ). The growing interest in discovering novel plant-based bioactive compounds has brought attention to fruits such as ficus carica , renowned for their traditional medicinal applications. The curative advantage of ficus carica has been reported in the conventional systems of medicine. It has shown several other medicinal properties like endocrine system, respiratory system, infectious diseases and extended research is in process to certify its traditional medicinal uses. This study examines the comparative analysis of bioactive compounds and health-promoting properties between wild and cultivated varieties of Ficus carica . It addresses a critical knowledge gap concerning the variability of these compounds within a single species. The findings contribute to the broader discourse on the role of functional foods and natural therapeutics in disease prevention and management, highlighting the potential of wild varieties as superior sources of bioactive metabolites for developing novel health interventions. Material and methods Eight ficus accessions, viz YL-G-01 Youngura Ganderbal, B-G-14 Babawayil Ganderbal, B-G-04 Babawayil Ganderbal, Wild − 01 Srinagar, DH-S-02 Dara Harwan Srinagar, AS-S-06 Arabal Shalimar Srinagar, DH-S-08 Dara Harwan Srinagar and Wild − 02 Ganderbal were taken at maturity stage. The maturity stage was determined based on standard horticultural indicators such as color change, fruit firmness and soluble solids content. All ficus varieties were sourced from Srinagar and Ganderbal areas of Kashmir valley located in Northern Himalayan regions India. These accessions were cultivated under different environmental conditions such as different soil types, irrigation practices and pest management protocols to explore the level of variability due to external factors. Sample Preparation: To prevent the oxidation of phenolic compounds, fruits from each Ficus cultivars were homogenized and quenched in liquid nitrogen at a ratio of 1:2 (w/v) (Mohamed et al., 2019 ). After this, the material was immediately freeze-dried, excluding the seeds. The freeze-dried fruit material was further homogenized by grinding it in a mortar. For the extraction process, 8 g of the powdered fruit sample was precisely weighed and placed into extraction tubes. 10 mL of acetone at predetermined concentrations were used for the extraction process. The samples were incubated at 10°C for 10–15 minutes to facilitate phenolic compound extraction. After incubation, the mixtures were centrifuged at 8160×g for 20 minutes using a centrifuge. The supernatants were concentrated by vacuum evaporation at 40°C using an IKA HB-10 rotary evaporator (IKA, Germany) and then lyophilized. The lyophilized extracts were re-dissolved in 3 mL of a solvent mixture containing 2.5% acetic acid and methanol in a 3:1 (v/v) ratio. This solution was filtered to remove particulate matter, making the extracts ready for subsequent analytical evaluations. Total Saponin Content: The procedure for determining the total saponin content was based on Wei et al. ( 2020 ). Initially, the samples were extracted three times with ethanol, and the resulting extracts were dried using a rotary evaporator set at 55°C. The dried ethanol extract was then dissolved in water and subjected to chloroform extraction to remove lipids. Following this, a final extraction was performed using n-butanol. The n-butanol extract was concentrated to a constant mass using rotary evaporation, and the total saponin content was determined by measuring the dry mass of the n-butanol extract. Determination of Alkaloids: The presence of alkaloids was determined using Dragendorff's method, as described by Singh et al. ( 2017 ). A portion of the extract was dissolved in diluted hydrochloric acid, and two drops of Dragendorff's reagent were added. The formation of a crystalline precipitate indicated the presence of alkaloids. Estimation of Phenols: The total phenolic content was determined according to the method described by Uniyal et al. ( 2006 ). Absorbance readings were taken at 760 nm using a UV-VIS spectrophotometer. The phenolic content was quantified in milligrams of gallic acid equivalents (mg GAE) per gram of fresh weight. Estimation of Tannins: The total tannin content was assessed using an adapted method based on Xu and Chang (Lai and Roy, 2004 ). Absorbance readings were recorded at 500 nm, and the tannin content was quantified in milligrams of catechin equivalents (mg CE) per gram of fresh weight. Determination of Antioxidant Activity: DPPH Assay: The DPPH activity was estimated by employing a modified method from Olimpia et al. ( 2018 ). Absorbance was taken at 517 nm with a UV/VIS spectrophotometer (Labomed, USA). The percentage inhibition of free radicals was calculated using the formula: % inhibition = 100 × (Absorbance of blank - Absorbance of sample) / Absorbance of blank. FRAP: The Ferric Reducing Antioxidant Power (FRAP) activity was examined by following the protocol outlined by Akin et al. ( 2008 ). Absorbance was measured at 593 nm after 4 minutes, and the FRAP value was expressed in millimoles of ferrous ion (Fe²⁺) equivalents per gram of fresh weight, using a standard calibration curve with ferrous sulfate. HPLC Analysis: The phenolic compounds in the wild and cultivated Ficus varieties were quantified using an HPLC system (Shimadzu). The method, adapted from Karav and Eksi ( 2012 ), was utilized to test catechin and epicatechin at 280 nm, coumaric acid at 345 nm, and rutin at 260 nm. The mobile phase contained 2.5% HPLC-grade glacial acetic acid (Solvent A) and acetonitrile (Solvent B). The analysis was conducted with a 20 µL injection volume and a flow rate of 1.0 mL/min for 60 minutes. Samples were analysed in triplicate, and quantitative analysis was determined based on peak areas compared to standards, with concentrations reported in micrograms per gram (µg/g) of the sample. α-Amylase Inhibitory Assay: The α-amylase inhibitory effect was evaluated using a modified method by Bors et al. ( 1995 ). Absorbance was recorded at 540 nm. A blank solution was prepared by replacing the enzyme and inhibitor with 200 µL of buffer. The inhibitory activity was estimated using the formula: α- amylase inhibition (%) = (Abs Control – Abs Sample /Abs Control) × 100 α-Glucosidase Inhibitory Assay: The α-glucosidase inhibitory effect was assessed using a modified method from Rice Evans et al. (1996). Absorbance was measured at 405 nm before and after substrate addition. The inhibitory activity was calculated as a percentage of inhibition using the formula: α-glucosidase inhibition (%) = (Abs Control − Abs Sample/Abs Control) ×100 Acetylcholinesterase Inhibition: The enzymatic activity was evaluated using the modified procedure by Ou et al. ( 2002 ). The reaction was monitored at 405 nm for 5 minutes. Enzyme activity was compared to a control assay using buffer instead of the inhibitor, and the inhibitory effect was calculated using the following formula: I% = 100 - (A sample / A control) × 100, where A represents absorbance Cytotoxic Activity: Sample Preparation and Culturing of Cell Lines: Stock solutions of the extract were prepared at 20 mg/mL by dissolving them in DMSO. Cancer cell lines, such as PC-3 (prostate cancer), A-549 (lung cancer), MCF-7 (breast cancer), HeLa (cervical cancer), and HEK (kidney cancer), were sourced from the National Center for Cell Science in Pune, India, and the National Cancer Institute. The cell lines were cultured under standard conditions at 37°C. MTT Assay: The MTT assay, as depicted by Afshar et al. ( 2019 ) with slight changes, was used to assess cell proliferation inhibition. Absorbance was recorded at 590 nm, and percentage inhibition was estimated using the formula: I% = 100 - (A sample / A control) × 100, where A represents absorbance Statistical Analysis: Detailed statistical evaluations, encompassing correlation analysis and Principal Component Analysis (PCA), were conducted on triplicate data sets to ensure robustness and reproducibility. Results were presented as mean ± SD (Standard Deviation). The R software framework was used for the analysis. Pearson’s correlation test was employed to determine correlation coefficients, and IC 50 values (the concentration at which 50% inhibition was observed) were calculated using GraphPad Prism version 5.0. Results and Discussion The comparative analysis of the cultivars revealed notable differences in their antioxidant properties and phytochemical profiles, with Wild − 02 Ganderbal emerging as the most exceptional among them (Table 1 ). This cultivar leads with the highest phenolic content (237.23 mg GAEs/g FW) and the lowest DPPH IC 50 value (12.32 µg/g FW), indicating superior antioxidant activity and effectiveness in scavenging free radicals. Its FRAP value (9.62 mM Fe2 + eq./g FW) also ranks highest, reflecting strong reducing power. These attributes, combined with high levels of tannins, alkaloids, and saponins, underscore its potential for health applications due to its potent antioxidant and nutritional benefits. In comparison, Wild − 01 Srinagar also demonstrates robust antioxidant properties with a high phenolic content (206.37 mg GAEs/g FW) and a low DPPH IC 50 value (21.03 µg/g FW). While its antioxidant activity is somewhat lower than that of Wild − 02, it still shows substantial effectiveness and a strong FRAP value (7.76 mM Fe 2+ eq./g FW). This cultivar’s balanced levels of tannins, saponins, and moderate alkaloid content make it a noteworthy option for health-related research. DH-S-02 Dara Harwan Srinagar and DH-S-08 Dara Harwan Srinagar also exhibit considerable antioxidant activity. DH-S-02 has a high phenolic content (196.40 mg GAEs/g FW) and a respectable FRAP value (4.38 mM Fe 2+ eq./g FW), with significant alkaloid content. Variety YL-G-01 Youngura Ganderbal shows the lowest phenolic content (93.13 mg GAEs/g FW) and the highest DPPH IC 50 value (132.03 µg/g FW), indicating the least antioxidant activity and weakest reducing power (0.99 mM Fe 2+ eq./g FW). Its lower levels of tannins, alkaloids, and saponins further limit its potential compared to other cultivars. In summary, while Wild − 02 Ganderbal stands out for its exceptional antioxidant properties and phytochemical richness. This differential performance highlights Wild − 02 as the most promising for health-related applications, with other cultivars like Wild − 01 and DH-S-02 also showing considerable benefits. To provide a comprehensive comparison of our results with those of previous studies, we reviewed the existing literature on antioxidant properties and phytochemical profiles. The high phenolic content (237.23 mg GAEs/g FW) and strong antioxidant activity of Wild − 02 Ganderbal (lowest DPPH IC 50 value of 12.32 µg/g FW, highest FRAP value of 9.62 mM Fe 2+ eq./g FW) align with studies highlighting the benefits of high phenolic content in enhancing antioxidant properties. For example, studies by Kaur et al. ( 2021 ) and Pandey & Rizvi ( 2009 ) demonstrate that high phenolic content correlates with strong antioxidant activities and reduced oxidative stress in various plant species. Similar variability in antioxidant potential among cultivars has been previously documented, suggesting influences of genetic differences, environmental conditions, and maturity stages on antioxidant capacity (Akin et al., 2008 ; Karav and Eksi 2012 ). The antioxidant properties of fruit extracts may be attributed to their polyphenolic content, which is known for its effective radical scavenging actions (Bors et al., 1995 ; Rice-Evans et al., 1996 ; Ou et al., 2002 ). Methanolic extracts may exhibit higher antioxidant activities due to the presence of flavonoids and their ability to donate hydrogen atoms. Previous research has indicated that medicinal plants rich in polyphenolic compounds tend to exhibit pronounced antioxidant properties (Afshar et al., 2019 ; Harassi et al., 2019 ; Kaurinovic et al., 2019; Ruvanthika et al., 2019). Moreover, the presence of secondary metabolites such as tannins, glycosides, and alkaloids in the extracts might augment their capacity to combat oxygen and often contribute to their significant therapeutic properties and medicinal value (Lai and Roy, 2004 ). By comparing these results with existing litrature, it is evident that Wild − 02 Ganderbal exhibits exceptional antioxidant properties, reinforcing the significance of high phenolic content in enhancing antioxidant activity. Conversely, YL-G-01 Youngura Ganderbal’s lower antioxidant potential aligns with other studies highlighting the impact of reduced phenolic content on antioxidant activity. This comparison helps to validate the findings and suggests that cultivars with high phenolic content and antioxidant activity, such as Wild − 02, are most promising for health applications. Table 1 Data represents the variability in the phytochemical composition and antioxidant potential of diverse ficus cultivars. Cultivar Phenols (mg GAEs/g FW) Tanins Alkaloids Saponins DPPH IC 50 (µg/g FW) FRAP mM Fe 2+ eq./g FW YL-G-01 Youngura Ganderbal 93.13 ± 31.25 ++ + + 132.03 ± 22.25 0.99 ± 1.25 B-G-14 Babawayil Gandebal 160.39 ± 33.25 + ++ + 79.68 ± 19.25 1.79 ± 1.95 B-G-04 Babawayil Gandebal 142.62 ± 30.15 ++ ++ ++ 108.01 ± 18.25 2.41 ± 2.25 Wild − 01 Srinagar 206.37 ± 29.5 +++ ++ ++ 21.03 ± 25.65 7.76 ± 3.25 DH-S-02 Dara Harwan Srinagar 196.40 ± 31.00 ++ +++ ++ 86.21 ± 25.36 4.38 ± 5.25 AS-S-06 Arabal Shalimar Srinagar 112.52 ± 31.45 + ++ + 104.25 ± 31.25 2.98 ± 6.25 DH-S-08 Dara Harwan Srinagar 122.66 ± 27.25 ++ + ++ 64.06 ± 31.35 4.27 ± 7.25 Wild − 02 Ganderbal 237.23 ± 28.25 +++ ++ +++ 12.32 ± 31.17 9.62 ± 5.25 The data is represented in mean SD± (n = 3) HPLC Analysis The data presented in Table 2 elucidates the variability in concentrations of several phenolic compounds viz catechin, epicatechin, quercetin, coumaric acid, and rutin—across wild and cultivated ficus cultivars, revealing distinct phytochemical profiles with implications for health benefits and applications. Wild − 02 Ganderbal demonstrates the highest levels of catechin (341 µg/g FW) and epicatechin (504 µg/g FW), alongside the highest concentrations of quercetin (258 µg/g FW) and coumaric acid (997 µg/g FW). Additionally, it has a notably elevated rutin content (146 µg/g FW). Wild − 01 Srinagar also shows substantial levels of quercetin (226 µg/g FW) and coumaric acid (457 µg/g FW), along with moderate catechin (86 µg/g FW) and epicatechin (294 µg/g FW). Its rutin content (142 µg/g FW) is significant. AS-S-06 Arabal Shalimar Srinagar variety dipicted a high concentration of catechin (153 µg/g FW) and quercetin (181 µg/g FW), but lower levels of epicatechin (65 µg/g FW) and coumaric acid (86 µg/g FW). Its rutin content (31 µg/g FW) was found relatively low. B-G-04 Babawayil Gandebal revealed moderate levels of catechin (56 µg/g FW) and epicatechin (72 µg/g FW), with low quercetin levels and moderate coumaric acid (127 µg/g FW) and rutin (36 µg/g FW). B-G-14 Babawayil Gandebal showed moderate levels of catechin (63 µg/g FW), epicatechin (58 µg/g FW), and rutin (38 µg/g FW), with relatively lower quercetin (32 µg/g FW) and coumaric acid (241 µg/g FW). DH-S-02 Dara Harwan Srinagar presented lower levels of catechin (37 µg/g FW), quercetin (31 µg/g FW), and coumaric acid (153 µg/g FW), with moderate epicatechin (56 µg/g FW) and rutin (40 µg/g FW). DH-S-08 Dara Harwan Srinagar showed the lowest levels of catechin (26 µg/g FW) and rutin (12 µg/g FW), with moderate levels of epicatechin (67 µg/g FW), quercetin (53 µg/g FW), and coumaric acid (314 µg/g FW). Variety YL-G-01 Youngura Ganderbal exhibited relatively high levels of catechin (94 µg/g FW) and epicatechin (72 µg/g FW), with moderate quercetin (65 µg/g FW), high coumaric acid (326 µg/g FW), and lower rutin (25 µg/g FW). This variability underscores the diverse health benefits offered by different Ficus cultivars, highlighting the importance of cultivar-specific profiles in assessing their antioxidant and therapeutic potential. The unique profile of phenolic compounds in fruits varies by species and genotype, serving as a useful marker for chemotaxonomic classification. (Ou et al., 2002 ; Gazdik et al., 2008 ). Additionally, the polyphenolic content is influenced by the specific cultivar and its genetic composition (Matthes and Schmitz-Eiberger, 2009 ). The polyphenols identified in various ficus species in this study could contribute to the observed health benefits, as previous research has linked these flavanols to significant pharmacological effects (Matthes and Schmitz-Eiberger, 2012 ) Table 2 Data represents the variability of different bioactive molecules in ficus cultivars. Cultivar Catechin (ug/gFW) Epicatechin (ug/gFW) Quercetin (ug/gFW) Coumaric acid (ug/gFW) Rutin (ug/gFW) YL-G-01 Youngura Ganderbal 94.00 ± 33.25 72.00 ± 14.25 65.00 ± 31.55 326.00 ± 44.68 25.00 ± 14.62 B-G-14 Babawayil Gandebal 63.00 ± 45.25 58.00 ± 18.55 32.00 ± 17.59 241.00 ± 40.92 38.00 ± 13.43 B-G-04 Babawayil Gandebal 56.00 ± 53.25 72.00 ± 15.58 Nd 127.00 ± 28.17 36.00 ± 11.87 Wild − 01 Srinagar 86.00 ± 33.58 294.00 ± 21.11 226.00 ± 23.51 457.00 ± 55.74 142.00 ± 19.27 DH-S-02 Dara Harwan Srinagar 37.00 ± 14.25 56.00 ± 13.82 31.00 ± 34.80 153.00 ± 27.67 40.00 ± 17.19 AS-S-06 Arabal Shalimar Srinagar 153.00 ± 22.15 65.00 ± 23.32 181.00 ± 15.42 86.00 ± 11.82 31.00 ± 3.09 DH-S-08 Dara Harwan Srinagar 26.00 ± 11.82 67.00 ± 13.83 53.00 ± 1.55 314.00 ± 27.97 12.00 ± 9.29 Wild − 02 Ganderbal 341.00 ± 26.12 504.00 ± 16.55 258.00 ± 12.25 997.00 ± 28.65 146.00 ± 15.21 The data is represented in mean SD± (n = 3) Acetyl cholinesterase, α- glucosidase and α- amylase inhibitory activity Figure 1 provides detailed insights into the inhibitory potential of ficus fruit extracts against three key enzymes—ACE (Angiotensin-Converting Enzyme), alpha-glucosidase, and alpha-amylase—at a concentration of 100 µg/mL. This information is essential for comparing the potential of wild and cultivated ficus extracts in regulating Alzheimer’s disease and Diabetes. Wild − 02 Ganderbal is highlighted as the most effective cultivar in terms of enzyme inhibition. It demonstrates the highest ACE inhibitory activity at 87.13%, suggesting strong potential for managing Alzheimer’s disease (Kong et al., 2016 ). Additionally, Wild − 02 exhibits substantial inhibition of alpha-glucosidase (85.59%) and alpha-amylase (90.71%), indicating its potential in controlling postprandial blood glucose levels by slowing carbohydrate digestion and absorption (Abdollahi et al., 2020 ). This comprehensive inhibitory profile positions Wild − 02 Ganderbal as a promising candidate for both Alzheimer’s disease and diabetes management, aligning with findings that effective enzyme inhibition can lead to better control of these conditions (Kumar et al., 2019 ). Wild − 01 Srinagar also shows significant enzyme inhibitory activities. It showed an ACE inhibitory activity of 80.98%, Furthermore, its alpha-glucosidase (86.74%) and alpha-amylase (84.12%) inhibition levels suggest a strong capacity for controlling blood glucose levels, though slightly less effective than Wild − 02. Similar research supports that high alpha-glucosidase and alpha-amylase inhibition is associated with improved glycemic control, which is beneficial for diabetes management (Sreelatha & Padma, 2009 ). Among the cultivated ficus varieties AS-S-06 Arabal Shalimar Srinagar presents a balanced enzyme inhibitory profile with moderate ACE inhibition (62.33%), alpha-glucosidase inhibition (53.37%), and alpha-amylase inhibition (77.37%). DH-S-02 Dara Harwan Srinagar and DH-S-08 Dara Harwan Srinagar exhibit lower overall inhibitory activities. DH-S-08, with the lowest ACE inhibitory activity (25.03%) and relatively lower inhibition of alpha-amylase (66.57%), alongside moderate alpha-glucosidase inhibition (59.16%), indicates limited efficacy in managing both conditions. This supports findings that lower enzyme inhibition levels generally correspond to reduced therapeutic benefits (Lee et al., 2014 ). This variability underscores the diverse potential of ficus cultivars in addressing metabolic health conditions based on their enzyme inhibitory profiles. Anticancer activity Figure 2 provides a detailed illustration of the growth inhibition percentages exhibited by Ficus carica (commonly known as anjeer) fruit extracts when tested against various human cancer cell lines. The results underscore the significant anti-cancer potential of these fruit extracts. The findings highlight the differential anticancer efficacy of various Ficus carica cultivars. Specifically, the cultivar Wild-02 Ganderbal demonstrates potent growth inhibition, with notable inhibition rates of 85% in cervical (HeLa) cells, 89% in kidney (HEK) cells, 81% in lung (A-549) cells, 88% in prostate (PC-3) cells, and an exceptional 95% in breast (MCF-7) cells, indicating a broad-spectrum anticancer potential. Similarly, Wild-01 Srinagar exhibits significant inhibitory activity, particularly in breast (90%) and prostate (84%) cancer cell lines. In contrast, the B-G-04 Babawayil Ganderbal cultivar shows strong inhibition in kidney (79%) and prostate (73%) cells, while B-G-14 Babawayil Ganderbal presents moderate inhibition across most tested cell lines, with a peak inhibition of 81% in breast cancer cells. On the other hand, DH-S-02 Dara Harwan Srinagar reveals the lowest inhibition rates, particularly in cervical (17%) and prostate (19%) cells, indicating a markedly reduced efficacy against these cancer types. These observations underscore the variability in anticancer potency among different cultivars, with Wild varieties showing substantial promise for therapeutic application, particularly in breast and prostate cancers, while others exhibit more limited effects. The findings are corroborated by existing literature; research conducted by (Khan et al., 2017 ; Kumar et al., 2018 ) has documented significant antioxidant activity and cytotoxic effects of anjeer extracts on various cancer cell lines, including MCF-7, supporting the hypothesis that the cultivars assessed may harbor similar bioactive compounds contributing to their anticancer effectiveness. Furthermore, Saha et al., 2019 ) highlighted the variability in cytotoxicity across different Ficus carica cultivars, consistent with the results presented in Fig. 2 . Additionally, a comprehensive review by Ben Saad et al., 2020) underscores the presence of beneficial phytochemicals in Ficus carica that enhance its anticancer potential, aligning with the superior performance of Wild-02. Collectively, these results emphasize the critical need for evaluating wild anjeer cultivars to identify the most effective treatments for diverse cancer types. They also suggest avenues for further investigation into the underlying mechanisms of action and the potential for synergistic effects through combination therapies to enhance therapeutic efficacy. The higher content of bioactive compounds and enhanced therapeutic activities observed in wild varieties of plants compared to cultivated varieties, can be attributed to several key factors such as (a) Environmental Stress Responses : Wild plants frequently encounter a diverse array of environmental stresses that significantly influence their physiological and biochemical processes. These stresses include extreme temperatures, drought, soil nutrient variability, and high levels of ultraviolet (UV) radiation. In response to these challenging conditions, wild plants often enhance their production of secondary metabolites, which play crucial roles in their survival and adaptation. Extreme temperatures, both high and low, can have profound effects on plant physiology. In high-temperature conditions, plants may experience increased oxidative stress due to higher levels of reactive oxygen species (ROS). To counteract this stress, plants often upregulate the synthesis of antioxidant secondary metabolites such as phenolic compounds, flavonoids, and carotenoids. These compounds help neutralize ROS and protect cellular components from oxidative damage. Conversely, low temperatures can induce the accumulation of cryoprotectants and other metabolites that prevent ice formation and cellular damage (Wang et al., 2011). (b) Genetic diversity : Genetic diversity within plant populations plays a crucial role in determining the range and abundance of bioactive compounds they produce. Wild plant varieties typically exhibit higher genetic diversity compared to their cultivated counterparts. This variability stems from their exposure to a broad spectrum of environmental pressures and evolutionary forces, which continuously shape their genetic makeup. This genetic diversity enables wild plants to adapt to diverse and often challenging conditions by evolving a more extensive array of biochemical responses, including the production of secondary metabolites. (Degenhardt et al., 2009). (C) Soil Composition : Soil and nutrient availability are critical factors influencing plant growth and biochemical composition. Wild plants, which often thrive in diverse and nutrient-poor soils, have evolved adaptive strategies to cope with these challenging conditions. In contrast, cultivated plants are typically grown in soils that are enriched and optimized for agricultural productivity. This difference in soil conditions significantly impacts the production of bioactive compounds, which are often elevated in wild plants as a response to less favorable soil environments (Li et al., 2015 ) Statistical Analysis Principal Component Analysis (Fig. 3 ) biplot illustrates the distribution of various samples (plotted as dots) and their relationship with multiple variables (represented by arrows). The PCA biplot shows two dimensions: Dim1, which explains 60.6% of the variance, and Dim2, which accounts for 16.5% of the variance. Different samples are labeled based on locations like "DH-S-08 Dara Harwan Srinagar" and "Wild-02 Ganderbal." The sample points are plotted across the biplot. Samples like "DH-S-08 Dara Harwan Srinagar" are positioned towards the upper left, while samples like "Wild-01 Srinagar" and "Wild-02 Ganderbal" are located on the right side, indicating varying characteristics. Overall, the biplot highlights the variation among the different samples concerning the measured biochemical or cellular properties. The first two principal components explain a large portion of the variance in the data, with the distribution of samples showing differing characteristics based on their positioning in relation to the key variables. Figure 4 is a correlation plot showing the relationship between multiple variables and principal components (PCs). Each cell in the matrix indicates the strength and direction of the correlation between a variable (rows) and a principal component (columns, labeled Dim1 to Dim7). The intensity of the color and size of the circles represent the magnitude of the correlation, with the color scale ranging from dark blue (strong positive correlation) to dark red (strong negative correlation). Phenols and FRAP have strong positive correlations with Dim1 (large blue circles), indicating these variables are highly associated with the first principal component. MCF7, PC3 and other cell line activities show moderate positive correlations with higher dimensions (e.g., Dim3, Dim4), with MCF7 having a strong positive correlation with Dim1. This plot provides insight into how each variable contributes to the variance captured by the different principal components, with Dim1 explaining a significant portion of the variance for several key variables such as phenolic content and antioxidant activity. The pattern of correlations helps to understand the underlying structure of the dataset. In Fig. 5 , Scree plot explained the percentage of variance associated with each principal component obtained by drawing a graph between eigen values and principal component numbers. Screen plot displays eigen values in descending order, highlighting the elbow point where the eigen values stabilize. This indicates which components are significant to retain. PCA1 accounts for 60.6% of the variance, while PCA2 explains 16.5%. The remaining components show decreasing variability, with PCA3 at 10.3%, PCA4 at 5.7%, PCA5 at 5%, PCA6 at 1.6%, PCA7 at 0.2%. The concentration of data in PCA1 suggests it has superior performance, as a higher percentage of retained data correlates with better overall data performance. Conclusion This study provides a comprehensive comparative analysis of wild and cultivated Ficus carica cultivars, highlighting the significant therapeutic potential of wild varieties. Among these, Wild-02 Ganderbal stands out as a promising candidate for future pharmaceutical or dietary supplement development due to its exceptional bioactive compound profile. The research confirms a strong correlation between high phenolic content and enhanced antioxidant activity, aligning with previous studies that emphasize the health benefits of polyphenols. However, a more comprehensive evaluation of the bioactivity of individual compounds, as well as their synergistic interactions, is essential. Further investigation into these compounds, particularly in the context of disease management, is necessary to assess their viability for commercialization as pharmaceutical agents or dietary supplements, thus contributing to advances in healthcare paradigms. While in vitro assays provide valuable preliminary insights into the therapeutic potential of fruit extracts, they do not fully replicate the complex interactions that occur in vivo. Therefore, future research should incorporate animal models to validate the anti-cancer and anti-diabetic effects observed in vitro. Additionally, a deeper investigation into the molecular mechanisms underlying these therapeutic effects is critical. This can be achieved through transcriptomic, proteomic and metabolomic analyses, which would elucidate how bioactive compounds derived from wild plants interact with biological systems to exert their effects. Understanding these mechanisms will be key to advancing the application of these compounds in therapeutic contexts. Declarations Conflicts of interest: The authors have no conflicts of interest to this work. Author Contribution ZNS: Conceptualisation, Methodology, Data curation, Validation, Formal analysis, Investigation, Resources, Visualisation, Writing – original draft; NS: Conceptualisation, Validation,Writing – review and editing; VS: Validation, Writing – review and editing, Supervision;PB:Validation, Writing – review and editing, Supervision;SR: Conceptualisation, Validation,Writing – review and editing; FSA: Investigation, Resources.All authors reviewed the manuscript. Acknowledgment: This research work was funded by Institutional Fund Project under grant no. (RSPD2024R693). The authors gratefully acknowledge King Saud University, Riyadh, Saudi Arabia. Data Availability Statement: The data presented in this study are available on request from the corresponding author. References Abdollahi M et al (2020) Alpha-glucosidase and alpha-amylase inhibitory activities of some medicinal plants used in Iran. J Ethnopharmacol 259:112941 Afshar FH, Delazar A, Nazemiyeh H et al (2019) Comparison of the total phenol, flavonoid contents and antioxidant activity of methanolic extracts of Artemisia spicigera and A. splendens growing in Iran. Pharm Sci 18(3):165–170 Akin EB, Karabulut I, Topcu A (2008) Some compositional properties of main Malatya apricot (Prunus armeniaca L.) varieties. Food Chem 107(2):939–948 Bors W, Michel C, Schikora S (1995) Interaction of flavonoids with ascorbate and determination of their univalent redox potentials: A pulse radiolysis study. Free Radic Biol Med 19(1):45–52 Bors W, Saran M, Michel C (2008) Antioxidant properties of flavonoids and phenolic compounds. Free Radic Res 42(8):792–804 Degenhardt J, Harrison RRTWNPW (2009) R. W. Miller. Genetic variation and secondary metabolite production in wild and cultivated plants. J Agric Food Chem 57(9):3825–3832 Dourado F, Van den Berg C, Gama M (2016) European Regulatory Framework on Novel Foods and Novel Food Additives. Bacterial Nanocellulose Biotechnol. Bio-Econ 8:135–144 Ganeshpurkar A, Saluja AK (2017) The pharmacological potential of rutin. Saudi Pharm J 25(2):149–164 Gazdik Z, Reznicek V, Adam V, Zitka O, Jurikova T, Krska B, Matuskovic J, Plsek J, Saloun J, Horna A, Kizek R (2008) Use of Liquid Chromatography with Electrochemical Detection for the Determination of Antioxidants in Less Common Fruits. Molecules 13:2823–2836 Harassi Y, Tilaoui M, Idir A et al (2019) Phytochemical analysis, cytotoxic and antioxidant activities of myrtuscommunis essential oil from Morocco. Journal of Complementary and Integrative Medicine , 16(3), 1–8. in Chitrakadivati by UV-Spectrophotometer. AncSci Life. 31(4), 198–201 Karav S, Eksi A (2012) Antioxidant capacity and total phenolic contents of peach and apricot cultivars harvested from different regions of turkey. Int J food Nutr Sci 4:13–17 Kaur C, Kapoor H, Ghosh A (2021) Antioxidant and phytochemical properties of medicinal plants. Phytother Res 35(4):1536–1547 Kaurinovic B, Vastag D (2019) Flavonoids and phenolic acids as potential natural antioxidants. Antioxidants. Intech Open, London UK, pp 1–20 Khan M, Riaz M, Ahmed N (2017) Assessment of antioxidant and phytochemical content of selected plant species. Int J Environ Res Public Health 14(9):1–10 Kong W et al (2016) ACE inhibition and antihypertensive effects of fruit and vegetable extracts. Food Chem 194:482–489 Kumar R et al (2019) Effects of natural inhibitors on key metabolic enzymes. J Med Plants Res 13(5):70–80 Kumar S et al (2018) Anti-cancer potential of Prunus armeniaca extracts and their underlying mechanisms. J Cancer Res Clin Oncol 144(8):1567–1576 Kwiatkowski P, Mnichowska-Polanowska M, Pruss A, Masiuk H, Dzi ˛ecioł M, Giedrys-Kalemba S, Sienkiewicz M (2017) The effect of fennel essential oil in combination with antibiotics on Staphylococcus aureus strains isolated from carriers. Burns 43:1544–1551 Lai PK, Roy J (2004) Antimicrobial and chemopreventive properties of herbs and spices. Curr Med Chem 11(11):1451–1460 Lai PK, Roy J (2004) Antimicrobial and chemopreventive properties of herbs and spices. Curr Med Chem 11(11):1451–1460 Lee YK et al (2014) Therapeutic potentials of enzyme inhibitors in managing chronic diseases. Front Pharmacol 5:70 Li X, Liu Y, Zhou Z (2015) Nutrient availability and its impact on secondary metabolite production in plants. Plant Physiol Biochem 89:77–83 Liang JY, Xu J, Yang YY, Shao YZ, Zhou F, Wang JL (2020) Toxicity and Synergistic Effect of Elsholtziaciliata Essential Oil and Its Main Components against the Adult and Larval Stages of Tribolium Castaneum. Foods 9:345 Matthes A, Schmitz-Eiberger M (2009) Apple (Malusdomestica L. Borkh.) allergen Mal d 1: effect of cultivar, cultivation system, and storage conditions. J Agric Food Chem 57(22):10548–10553 Matthes A, Schmitz-Eiberger M (2012) Polyphenol content and antioxidant capacity of apple fruit: effect of cultivar and storage conditions. J Appl Bot Food Qual 82(2):152–157 Mohamed M, El A, Ashour AS, Sadek A, Melad G (2019) A review on saponins from medicinal plants: chemistry, isolation, and determination. 7(4):282–288 Olimpia A, Alexa E, Lalescu D, Berbecea A, Camen D, Mariana P, Moigradean A, D., &, Bala M (2018) Chemical composition and antioxidant activity of some apricot varieties at different ripening stages. Chil J agricultural Res 78(2):266–275 Ou BX, Huang DJ, Hampsch-Woodill M, Flanagan JA, Deemer EK (2002) Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: A comparative study. J Agric Food Chem 50:3122–3128 Ou BX, Huang DJ, Hampsch-Woodill M, Flanagan JA, Deemer EK (2002) Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: A comparative study. J Agric Food Chem 50:3122–3128 Pandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev 2(5):270–278 Pellegrini M, Ricci A, Serio A, Chaves-López C, Mazzarrino G, D’Amato S, Sterzo L, C., &, Paparella A (2018) Characterization of Essential Oils Obtained from Abruzzo Autochthonous Plants, vol 7. Antioxidant and Antimicrobial Activities Assessment for Food Application. Foods, p 19 Poverenov E, Plumb NS, Anderson LD (2014) Secondary metabolite production in wild versus cultivated plants: A comparative study. Planta 240.2 : 405–418 Rice-Evans CA, Miller NJ, Paganga G (1996) Structure antioxidant activity relationship of flavonoids and phenolic acids. Free Radical Biol Med 20:933–956 Ruvanthika PN, &Manikandan SA (2019) Study on antioxidant activity, phenol, and flavonoid content of seedpod of Nelum bonucifera Gaertn. Drug Invent Today 11(4):835–840 Saha P, Talukdar AD, Nath R, Sarker SD, Nahar L, Sahu J, Choudhury MD (2019) Role of natural phenolics in hepatoprotection: a mechanistic review and analysis of regulatory network of associated genes. Front Pharmacol 10:509 Singh P, Singh G, Bhandawat A, Singh G, Parmar R, Seth R, Sharma RK (2017) Spatial transcriptome analysis provides insights of key gene(s) involved in steroidal saponin Sreelatha S, Padma PR (2009) Antioxidant and enzyme inhibitory activities of Prunus armeniaca. J Food Sci 74(7):H227–H233 Sun B, Wang J (2017) Food additives. In Food Safety in China. Part 3 Food Chemistry. In Food Additives; Jean, J.J., Chen, J., Eds.; John Wiley & Sons: Hoboken, NJ, USA, pp. 185–200 Uniyal SK, Singh KN, Jamwal P, Lal B (2006) Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya. J Ethnobiol Ethnomed 2:1–8 Wang Z, Zhang L, Zeng X (2008) Selective breeding effects on secondary metabolite levels in cultivated plants. Front Plant Sci 9:465 Wei G, Yang F, Wei F, Zhang L, Gao Y, Qian J, Chen Z, Jia Z, Wang Y, Su H, Dong L, Xu J, Chen S (2020) Metabolomes and transcriptomes revealed the saponin distribution in root tissues of Panaxquinque folius and Panaxnotoginseng. J Ginseng Res 44(6):757–769. https://doi.org/10.1016/j.jgr.2019.05.009 Additional Declarations No competing interests reported. Supplementary Files floatimage1.jpeg Graphical Abstract Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5334005","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":372080837,"identity":"068abd0c-dd56-460d-a120-0a7de0762da0","order_by":0,"name":"Zahid Nabi Sheikh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYDACCQaGg40NDAwGzAzGj//+sQEKMTYeIFaLmQFvQxpISwNBLYxgLUAkwdtwGCyIV4v87OaDB2fuqJM3Z2feYCC547zd2vbDQFtqbKJxaTG4cyzh4MYzbIY7m9kKHhieuZ287UwiUMuxtNwGXFokcgwOPmzjYdxwmMfAIIHtdrLZAaAWxobDOLXIz8j/ANQiYQ/SInGA7Vyy2fmH+LUw3MhhOLixzSARpEWyse2AndkNArYY3EgzODizLSF5w2G2MmOGM8kJZjeAtiTg8Yv8jOTHH3vb6mw3nD+8+TFDhZ292fn0hw8+1Njgdhg6SASrTCBWOQjYk6J4FIyCUTAKRgYAAPKQbXeXB9wWAAAAAElFTkSuQmCC","orcid":"","institution":"Sher-e-Kashmir University of Agricultural Sciences and Technology","correspondingAuthor":true,"prefix":"","firstName":"Zahid","middleName":"Nabi","lastName":"Sheikh","suffix":""},{"id":372080838,"identity":"a6835eed-849d-423d-a953-1ac8074b93df","order_by":1,"name":"Neha Sharma","email":"","orcid":"","institution":"Sher-e-Kashmir University of Agricultural Sciences and Technology","correspondingAuthor":false,"prefix":"","firstName":"Neha","middleName":"","lastName":"Sharma","suffix":""},{"id":372080839,"identity":"26ff0175-f7ee-4949-90d0-e72ad36ce2a3","order_by":2,"name":"Vikas Sharma","email":"","orcid":"","institution":"Sher-e-Kashmir University of Agricultural Sciences and Technology","correspondingAuthor":false,"prefix":"","firstName":"Vikas","middleName":"","lastName":"Sharma","suffix":""},{"id":372080840,"identity":"7a58d475-f1a3-462a-b905-6a2efec7b6d2","order_by":3,"name":"Parshant Bakshi","email":"","orcid":"","institution":"Sher-e-Kashmir University of Agricultural Sciences and Technology","correspondingAuthor":false,"prefix":"","firstName":"Parshant","middleName":"","lastName":"Bakshi","suffix":""},{"id":372080841,"identity":"0cb5d78f-c61a-4d9d-928b-c0c4a12b607c","order_by":4,"name":"Shilpa Raina","email":"","orcid":"","institution":"Shri Venkateshwara University","correspondingAuthor":false,"prefix":"","firstName":"Shilpa","middleName":"","lastName":"Raina","suffix":""},{"id":372080842,"identity":"3b5f0ba4-f5ab-4e36-8a8b-9687c55c50b9","order_by":5,"name":"Farid S Ataya","email":"","orcid":"","institution":"King Abdulaziz University","correspondingAuthor":false,"prefix":"","firstName":"Farid","middleName":"S","lastName":"Ataya","suffix":""}],"badges":[],"createdAt":"2024-10-25 17:38:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5334005/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5334005/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68388003,"identity":"2b5f201b-b94c-4540-87bf-bb1c27695c11","added_by":"auto","created_at":"2024-11-06 18:11:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16694,"visible":true,"origin":"","legend":"\u003cp\u003eInhibitory potential of different \u003cem\u003eficus ciraca\u003c/em\u003e fruit extracts.\u003c/p\u003e\n\u003cp\u003eValues are the mean ± SD (n = 3).\u003c/p\u003e","description":"","filename":"Onlinedrawingimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/b404b125ca7857015d4e8330.png"},{"id":68387413,"identity":"6e655f6b-b55e-49e6-a083-0d0f4b76968d","added_by":"auto","created_at":"2024-11-06 18:03:52","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":624480,"visible":true,"origin":"","legend":"\u003cp\u003eGraphs represent \u003cem\u003einvitro\u003c/em\u003e cytotoxic potential of different cultivars of \u003cem\u003eficus ciraca\u003c/em\u003efruit extracts at concentration 20 μg/mL.\u003c/p\u003e\n\u003cp\u003eValues are the mean ± SD (n = 3).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/888fd29618f13c951c46ed59.jpeg"},{"id":68387412,"identity":"541dba42-00be-4d9d-9901-b3afab29804d","added_by":"auto","created_at":"2024-11-06 18:03:52","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":357072,"visible":true,"origin":"","legend":"\u003cp\u003ePCA biplot visualizing the relationships between various \u003cem\u003eFicus carica\u003c/em\u003e cultivars and their bioactive properties, as represented by principal components (Dim1 and Dim2)\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/e9e5dfe48a4b7265838e9cd3.jpeg"},{"id":68387411,"identity":"26480071-77b5-45ab-a0d8-0072f8aa5bb1","added_by":"auto","created_at":"2024-11-06 18:03:51","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":40143,"visible":true,"origin":"","legend":"\u003cp\u003eVariable contribution and correlation with PCs.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/f3ee14438fd2d61caa5d2fea.png"},{"id":68387414,"identity":"954f8b9b-c09e-4b4b-ade1-c0a41e8a7fce","added_by":"auto","created_at":"2024-11-06 18:03:52","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":21234,"visible":true,"origin":"","legend":"\u003cp\u003eScree plot showing eigen value and cumulative variability of studied parameters\u003c/p\u003e","description":"","filename":"floatimage521.png","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/5508e30a35a2383a25fa3a88.png"},{"id":73307765,"identity":"fb2065b8-42d3-46aa-8998-21cf6a487006","added_by":"auto","created_at":"2025-01-08 17:31:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1693029,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/10e65ca0-091a-43f1-9987-f0b2d5c99d2a.pdf"},{"id":68387416,"identity":"abd4acfe-5b5e-4db8-892a-9d8354bf804b","added_by":"auto","created_at":"2024-11-06 18:03:52","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":525658,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical Abstract\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5334005/v1/a9e8e627059caebbec451e56.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Analysis of Bioactive Compounds and Health Benefits of Wild and Cultivated Ficus carica Accessions from the Northern Himalayas","fulltext":[{"header":"Research highlights","content":"\u003cul\u003e\n \u003cli\u003eWild-02 Ganderbal exhibited the highest antioxidant activity, phenolic content, and enzyme inhibition, making it a promising candidate for pharmaceutical and dietary applications.\u003c/li\u003e\n \u003cli\u003eComparative HPLC analysis showed Wild variety leading in catechin, epicatechin, quercetin, and coumaric acid concentrations, underscoring its rich phytochemical profile.\u003c/li\u003e\n \u003cli\u003eWild-02 Ganderbal demonstrated potent anticancer activity, particularly against breast and prostate cancer cell lines, achieving up to 95% inhibition in MCF-7 cells, outperforming cultivated varieties\u003c/li\u003e\n \u003cli\u003eGenetic diversity, environmental stress, and soil composition in wild cultivars contribute to their superior bioactive compound content and enhanced therapeutic properties.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eFor centuries, humans have utilized plants for drug development, with the traditional use of natural products in disease treatment emphasizing the need to explore plants for novel therapeutic agents. The medicinal value of plants is primarily attributed to their phytochemical compounds, which exert various physiological effects on the human body (Dourado et al \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Sun and wang, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Recently, scientific interest in the bioactivities of these natural compounds has intensified. Wild plants, in particular, tend to contain higher concentrations of bioactive compounds and exhibit stronger therapeutic properties than their cultivated counterparts. This advantage arises from their unique environmental adaptations and stress-response mechanisms. Exposure to a range of abiotic stresses, including extreme temperatures, pathogen pressure and nutrient deficiencies, drives wild plants to produce an array of secondary metabolites such as alkaloids and phenolics. These metabolites, evolved to defend against herbivores and pathogens, contribute to the plants' enhanced medicinal potential. Additionally, the evolutionary pressures in wild environments maintain high genetic diversity, leading to greater metabolite variability. In contrast, cultivated plants, selectively bred for traits like yield, size or appearance, often suffer from reduced genetic diversity, which can result in a diminished production of secondary metabolites and, consequently, lower therapeutic efficacy (Degenhardt et al., 2009; Poverenov et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). As a result, evaluating the biological properties of medicinal plant extracts, especially wild plants, can lead to the discovery of innovative, safe and potent bioactive compounds with anticancer, antioxidant, and antidiabetic properties (Liang et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Pellegrini et al \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Bioactive compounds derived from plants are increasingly favored as natural alternatives in various sectors, such as pharmaceuticals, cosmetics, and food (Kwiatkowski et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). The growing interest in discovering novel plant-based bioactive compounds has brought attention to fruits such as \u003cem\u003eficus carica\u003c/em\u003e, renowned for their traditional medicinal applications. The curative advantage of \u003cem\u003eficus carica\u003c/em\u003e has been reported in the conventional systems of medicine. It has shown several other medicinal properties like endocrine system, respiratory system, infectious diseases and extended research is in process to certify its traditional medicinal uses. This study examines the comparative analysis of bioactive compounds and health-promoting properties between wild and cultivated varieties of \u003cem\u003eFicus carica\u003c/em\u003e. It addresses a critical knowledge gap concerning the variability of these compounds within a single species. The findings contribute to the broader discourse on the role of functional foods and natural therapeutics in disease prevention and management, highlighting the potential of wild varieties as superior sources of bioactive metabolites for developing novel health interventions.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003eEight ficus accessions, \u003cem\u003eviz\u003c/em\u003e YL-G-01 Youngura Ganderbal, B-G-14 Babawayil Ganderbal, B-G-04 Babawayil Ganderbal, Wild \u0026minus;\u0026thinsp;01 Srinagar, DH-S-02 Dara Harwan Srinagar, AS-S-06 Arabal Shalimar Srinagar, DH-S-08 Dara Harwan Srinagar and Wild \u0026minus;\u0026thinsp;02 Ganderbal were taken at maturity stage. The maturity stage was determined based on standard horticultural indicators such as color change, fruit firmness and soluble solids content. All ficus varieties were sourced from Srinagar and Ganderbal areas of Kashmir valley located in Northern Himalayan regions India. These accessions were cultivated under different environmental conditions such as different soil types, irrigation practices and pest management protocols to explore the level of variability due to external factors.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSample Preparation:\u003c/h2\u003e \u003cp\u003eTo prevent the oxidation of phenolic compounds, fruits from each \u003cem\u003eFicus\u003c/em\u003e cultivars were homogenized and quenched in liquid nitrogen at a ratio of 1:2 (w/v) (Mohamed et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). After this, the material was immediately freeze-dried, excluding the seeds. The freeze-dried fruit material was further homogenized by grinding it in a mortar. For the extraction process, 8 g of the powdered fruit sample was precisely weighed and placed into extraction tubes. 10 mL of acetone at predetermined concentrations were used for the extraction process. The samples were incubated at 10\u0026deg;C for 10\u0026ndash;15 minutes to facilitate phenolic compound extraction. After incubation, the mixtures were centrifuged at 8160\u0026times;g for 20 minutes using a centrifuge. The supernatants were concentrated by vacuum evaporation at 40\u0026deg;C using an IKA HB-10 rotary evaporator (IKA, Germany) and then lyophilized. The lyophilized extracts were re-dissolved in 3 mL of a solvent mixture containing 2.5% acetic acid and methanol in a 3:1 (v/v) ratio. This solution was filtered to remove particulate matter, making the extracts ready for subsequent analytical evaluations.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTotal Saponin Content:\u003c/h3\u003e\n\u003cp\u003eThe procedure for determining the total saponin content was based on Wei et al. (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Initially, the samples were extracted three times with ethanol, and the resulting extracts were dried using a rotary evaporator set at 55\u0026deg;C. The dried ethanol extract was then dissolved in water and subjected to chloroform extraction to remove lipids. Following this, a final extraction was performed using n-butanol. The n-butanol extract was concentrated to a constant mass using rotary evaporation, and the total saponin content was determined by measuring the dry mass of the n-butanol extract.\u003c/p\u003e\n\u003ch3\u003eDetermination of Alkaloids:\u003c/h3\u003e\n\u003cp\u003eThe presence of alkaloids was determined using Dragendorff's method, as described by Singh et al. (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). A portion of the extract was dissolved in diluted hydrochloric acid, and two drops of Dragendorff's reagent were added. The formation of a crystalline precipitate indicated the presence of alkaloids.\u003c/p\u003e\n\u003ch3\u003eEstimation of Phenols:\u003c/h3\u003e\n\u003cp\u003eThe total phenolic content was determined according to the method described by Uniyal et al. (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Absorbance readings were taken at 760 nm using a UV-VIS spectrophotometer. The phenolic content was quantified in milligrams of gallic acid equivalents (mg GAE) per gram of fresh weight.\u003c/p\u003e\n\u003ch3\u003eEstimation of Tannins:\u003c/h3\u003e\n\u003cp\u003eThe total tannin content was assessed using an adapted method based on Xu and Chang (Lai and Roy, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). Absorbance readings were recorded at 500 nm, and the tannin content was quantified in milligrams of catechin equivalents (mg CE) per gram of fresh weight.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDetermination of Antioxidant Activity:\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eDPPH Assay:\u003c/h2\u003e \u003cp\u003eThe DPPH activity was estimated by employing a modified method from Olimpia et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Absorbance was taken at 517 nm with a UV/VIS spectrophotometer (Labomed, USA). The percentage inhibition of free radicals was calculated using the formula:\u003c/p\u003e \u003cp\u003e% inhibition\u0026thinsp;=\u0026thinsp;100 \u0026times; (Absorbance of blank - Absorbance of sample) / Absorbance of blank.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eFRAP:\u003c/h3\u003e\n\u003cp\u003eThe Ferric Reducing Antioxidant Power (FRAP) activity was examined by following the protocol outlined by Akin et al. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Absorbance was measured at 593 nm after 4 minutes, and the FRAP value was expressed in millimoles of ferrous ion (Fe\u0026sup2;⁺) equivalents per gram of fresh weight, using a standard calibration curve with ferrous sulfate.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eHPLC Analysis:\u003c/h2\u003e \u003cp\u003eThe phenolic compounds in the wild and cultivated Ficus varieties were quantified using an HPLC system (Shimadzu). The method, adapted from Karav and Eksi (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2012\u003c/span\u003e), was utilized to test catechin and epicatechin at 280 nm, coumaric acid at 345 nm, and rutin at 260 nm. The mobile phase contained 2.5% HPLC-grade glacial acetic acid (Solvent A) and acetonitrile (Solvent B). The analysis was conducted with a 20 \u0026micro;L injection volume and a flow rate of 1.0 mL/min for 60 minutes. Samples were analysed in triplicate, and quantitative analysis was determined based on peak areas compared to standards, with concentrations reported in micrograms per gram (\u0026micro;g/g) of the sample.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eα-Amylase Inhibitory Assay:\u003c/h2\u003e \u003cp\u003eThe α-amylase inhibitory effect was evaluated using a modified method by Bors et al. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1995\u003c/span\u003e). Absorbance was recorded at 540 nm. A blank solution was prepared by replacing the enzyme and inhibitor with 200 \u0026micro;L of buffer. The inhibitory activity was estimated using the formula:\u003c/p\u003e \u003cp\u003eα- amylase inhibition (%) = (Abs Control \u0026ndash; Abs Sample /Abs Control) \u0026times; 100\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eα-Glucosidase Inhibitory Assay:\u003c/h2\u003e \u003cp\u003eThe α-glucosidase inhibitory effect was assessed using a modified method from Rice Evans et al. (1996). Absorbance was measured at 405 nm before and after substrate addition. The inhibitory activity was calculated as a percentage of inhibition using the formula:\u003c/p\u003e \u003cp\u003eα-glucosidase inhibition (%) = (Abs Control\u0026thinsp;\u0026minus;\u0026thinsp;Abs Sample/Abs Control) \u0026times;100\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAcetylcholinesterase Inhibition:\u003c/h2\u003e \u003cp\u003eThe enzymatic activity was evaluated using the modified procedure by Ou et al. (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). The reaction was monitored at 405 nm for 5 minutes. Enzyme activity was compared to a control assay using buffer instead of the inhibitor, and the inhibitory effect was calculated using the following formula:\u003c/p\u003e \u003cp\u003eI% = 100 - (A sample / A control) \u0026times; 100, where A represents absorbance\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCytotoxic Activity:\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003eSample Preparation and Culturing of Cell Lines:\u003c/h2\u003e \u003cp\u003eStock solutions of the extract were prepared at 20 mg/mL by dissolving them in DMSO. Cancer cell lines, such as PC-3 (prostate cancer), A-549 (lung cancer), MCF-7 (breast cancer), HeLa (cervical cancer), and HEK (kidney cancer), were sourced from the National Center for Cell Science in Pune, India, and the National Cancer Institute. The cell lines were cultured under standard conditions at 37\u0026deg;C.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMTT Assay:\u003c/h2\u003e \u003cp\u003eThe MTT assay, as depicted by Afshar et al. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) with slight changes, was used to assess cell proliferation inhibition. Absorbance was recorded at 590 nm, and percentage inhibition was estimated using the formula:\u003c/p\u003e \u003cp\u003eI% = 100 - (A sample / A control) \u0026times; 100, where A represents absorbance\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis:\u003c/h2\u003e \u003cp\u003eDetailed statistical evaluations, encompassing correlation analysis and Principal Component Analysis (PCA), were conducted on triplicate data sets to ensure robustness and reproducibility. Results were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (Standard Deviation). The R software framework was used for the analysis. Pearson\u0026rsquo;s correlation test was employed to determine correlation coefficients, and IC\u003csub\u003e50\u003c/sub\u003e values (the concentration at which 50% inhibition was observed) were calculated using GraphPad Prism version 5.0.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eThe comparative analysis of the cultivars revealed notable differences in their antioxidant properties and phytochemical profiles, with Wild \u0026minus;\u0026thinsp;02 Ganderbal emerging as the most exceptional among them (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This cultivar leads with the highest phenolic content (237.23 mg GAEs/g FW) and the lowest DPPH IC\u003csub\u003e50\u003c/sub\u003e value (12.32 \u0026micro;g/g FW), indicating superior antioxidant activity and effectiveness in scavenging free radicals. Its FRAP value (9.62 mM Fe2\u0026thinsp;+\u0026thinsp;eq./g FW) also ranks highest, reflecting strong reducing power. These attributes, combined with high levels of tannins, alkaloids, and saponins, underscore its potential for health applications due to its potent antioxidant and nutritional benefits. In comparison, Wild \u0026minus;\u0026thinsp;01 Srinagar also demonstrates robust antioxidant properties with a high phenolic content (206.37 mg GAEs/g FW) and a low DPPH IC\u003csub\u003e50\u003c/sub\u003e value (21.03 \u0026micro;g/g FW). While its antioxidant activity is somewhat lower than that of Wild \u0026minus;\u0026thinsp;02, it still shows substantial effectiveness and a strong FRAP value (7.76 mM Fe\u003csup\u003e2+\u003c/sup\u003e eq./g FW). This cultivar\u0026rsquo;s balanced levels of tannins, saponins, and moderate alkaloid content make it a noteworthy option for health-related research. DH-S-02 Dara Harwan Srinagar and DH-S-08 Dara Harwan Srinagar also exhibit considerable antioxidant activity. DH-S-02 has a high phenolic content (196.40 mg GAEs/g FW) and a respectable FRAP value (4.38 mM Fe\u003csup\u003e2+\u003c/sup\u003e eq./g FW), with significant alkaloid content. Variety YL-G-01 Youngura Ganderbal shows the lowest phenolic content (93.13 mg GAEs/g FW) and the highest DPPH IC\u003csub\u003e50\u003c/sub\u003e value (132.03 \u0026micro;g/g FW), indicating the least antioxidant activity and weakest reducing power (0.99 mM Fe\u003csup\u003e2+\u003c/sup\u003e eq./g FW). Its lower levels of tannins, alkaloids, and saponins further limit its potential compared to other cultivars. In summary, while Wild \u0026minus;\u0026thinsp;02 Ganderbal stands out for its exceptional antioxidant properties and phytochemical richness. This differential performance highlights Wild \u0026minus;\u0026thinsp;02 as the most promising for health-related applications, with other cultivars like Wild \u0026minus;\u0026thinsp;01 and DH-S-02 also showing considerable benefits. To provide a comprehensive comparison of our results with those of previous studies, we reviewed the existing literature on antioxidant properties and phytochemical profiles. The high phenolic content (237.23 mg GAEs/g FW) and strong antioxidant activity of Wild \u0026minus;\u0026thinsp;02 Ganderbal (lowest DPPH IC\u003csub\u003e50\u003c/sub\u003e value of 12.32 \u0026micro;g/g FW, highest FRAP value of 9.62 mM Fe\u003csup\u003e2+\u003c/sup\u003e eq./g FW) align with studies highlighting the benefits of high phenolic content in enhancing antioxidant properties. For example, studies by Kaur et al. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) and Pandey \u0026amp; Rizvi (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) demonstrate that high phenolic content correlates with strong antioxidant activities and reduced oxidative stress in various plant species. Similar variability in antioxidant potential among cultivars has been previously documented, suggesting influences of genetic differences, environmental conditions, and maturity stages on antioxidant capacity (Akin et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Karav and Eksi \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). The antioxidant properties of fruit extracts may be attributed to their polyphenolic content, which is known for its effective radical scavenging actions (Bors et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1995\u003c/span\u003e; Rice-Evans et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e1996\u003c/span\u003e; Ou et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). Methanolic extracts may exhibit higher antioxidant activities due to the presence of flavonoids and their ability to donate hydrogen atoms. Previous research has indicated that medicinal plants rich in polyphenolic compounds tend to exhibit pronounced antioxidant properties (Afshar et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Harassi et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Kaurinovic et al., 2019; Ruvanthika et al., 2019). Moreover, the presence of secondary metabolites such as tannins, glycosides, and alkaloids in the extracts might augment their capacity to combat oxygen and often contribute to their significant therapeutic properties and medicinal value (Lai and Roy, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). By comparing these results with existing litrature, it is evident that Wild \u0026minus;\u0026thinsp;02 Ganderbal exhibits exceptional antioxidant properties, reinforcing the significance of high phenolic content in enhancing antioxidant activity. Conversely, YL-G-01 Youngura Ganderbal\u0026rsquo;s lower antioxidant potential aligns with other studies highlighting the impact of reduced phenolic content on antioxidant activity. This comparison helps to validate the findings and suggests that cultivars with high phenolic content and antioxidant activity, such as Wild \u0026minus;\u0026thinsp;02, are most promising for health applications.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eData represents the variability in the phytochemical composition and antioxidant potential of diverse ficus cultivars.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCultivar\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhenols (mg GAEs/g FW)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTanins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAlkaloids\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSaponins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDPPH IC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e \u003cp\u003e(\u0026micro;g/g FW)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFRAP\u003c/p\u003e \u003cp\u003emM Fe\u003csup\u003e2+\u003c/sup\u003eeq./g FW\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYL-G-01 Youngura Ganderbal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e93.13\u0026thinsp;\u0026plusmn;\u0026thinsp;31.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e132.03\u0026thinsp;\u0026plusmn;\u0026thinsp;22.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-G-14 Babawayil Gandebal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e160.39\u0026thinsp;\u0026plusmn;\u0026thinsp;33.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e79.68\u0026thinsp;\u0026plusmn;\u0026thinsp;19.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-G-04 Babawayil Gandebal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e142.62\u0026thinsp;\u0026plusmn;\u0026thinsp;30.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e108.01\u0026thinsp;\u0026plusmn;\u0026thinsp;18.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.41\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild \u0026minus;\u0026thinsp;01 Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e206.37\u0026thinsp;\u0026plusmn;\u0026thinsp;29.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e21.03\u0026thinsp;\u0026plusmn;\u0026thinsp;25.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e7.76\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDH-S-02 Dara Harwan Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e196.40\u0026thinsp;\u0026plusmn;\u0026thinsp;31.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e86.21\u0026thinsp;\u0026plusmn;\u0026thinsp;25.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e4.38\u0026thinsp;\u0026plusmn;\u0026thinsp;5.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS-S-06 Arabal Shalimar Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e112.52\u0026thinsp;\u0026plusmn;\u0026thinsp;31.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e104.25\u0026thinsp;\u0026plusmn;\u0026thinsp;31.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e2.98\u0026thinsp;\u0026plusmn;\u0026thinsp;6.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDH-S-08 Dara Harwan Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e122.66\u0026thinsp;\u0026plusmn;\u0026thinsp;27.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e64.06\u0026thinsp;\u0026plusmn;\u0026thinsp;31.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e4.27\u0026thinsp;\u0026plusmn;\u0026thinsp;7.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild \u0026minus;\u0026thinsp;02 Ganderbal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e237.23\u0026thinsp;\u0026plusmn;\u0026thinsp;28.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e12.32\u0026thinsp;\u0026plusmn;\u0026thinsp;31.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e9.62\u0026thinsp;\u0026plusmn;\u0026thinsp;5.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe data is represented in mean SD\u0026plusmn; (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eHPLC Analysis\u003c/h2\u003e \u003cp\u003eThe data presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e elucidates the variability in concentrations of several phenolic compounds \u003cem\u003eviz\u003c/em\u003e catechin, epicatechin, quercetin, coumaric acid, and rutin\u0026mdash;across wild and cultivated \u003cem\u003eficus\u003c/em\u003e cultivars, revealing distinct phytochemical profiles with implications for health benefits and applications. Wild \u0026minus;\u0026thinsp;02 Ganderbal demonstrates the highest levels of catechin (341 \u0026micro;g/g FW) and epicatechin (504 \u0026micro;g/g FW), alongside the highest concentrations of quercetin (258 \u0026micro;g/g FW) and coumaric acid (997 \u0026micro;g/g FW). Additionally, it has a notably elevated rutin content (146 \u0026micro;g/g FW). Wild \u0026minus;\u0026thinsp;01 Srinagar also shows substantial levels of quercetin (226 \u0026micro;g/g FW) and coumaric acid (457 \u0026micro;g/g FW), along with moderate catechin (86 \u0026micro;g/g FW) and epicatechin (294 \u0026micro;g/g FW). Its rutin content (142 \u0026micro;g/g FW) is significant. AS-S-06 Arabal Shalimar Srinagar variety dipicted a high concentration of catechin (153 \u0026micro;g/g FW) and quercetin (181 \u0026micro;g/g FW), but lower levels of epicatechin (65 \u0026micro;g/g FW) and coumaric acid (86 \u0026micro;g/g FW). Its rutin content (31 \u0026micro;g/g FW) was found relatively low. B-G-04 Babawayil Gandebal revealed moderate levels of catechin (56 \u0026micro;g/g FW) and epicatechin (72 \u0026micro;g/g FW), with low quercetin levels and moderate coumaric acid (127 \u0026micro;g/g FW) and rutin (36 \u0026micro;g/g FW). B-G-14 Babawayil Gandebal showed moderate levels of catechin (63 \u0026micro;g/g FW), epicatechin (58 \u0026micro;g/g FW), and rutin (38 \u0026micro;g/g FW), with relatively lower quercetin (32 \u0026micro;g/g FW) and coumaric acid (241 \u0026micro;g/g FW). DH-S-02 Dara Harwan Srinagar presented lower levels of catechin (37 \u0026micro;g/g FW), quercetin (31 \u0026micro;g/g FW), and coumaric acid (153 \u0026micro;g/g FW), with moderate epicatechin (56 \u0026micro;g/g FW) and rutin (40 \u0026micro;g/g FW). DH-S-08 Dara Harwan Srinagar showed the lowest levels of catechin (26 \u0026micro;g/g FW) and rutin (12 \u0026micro;g/g FW), with moderate levels of epicatechin (67 \u0026micro;g/g FW), quercetin (53 \u0026micro;g/g FW), and coumaric acid (314 \u0026micro;g/g FW). Variety YL-G-01 Youngura Ganderbal exhibited relatively high levels of catechin (94 \u0026micro;g/g FW) and epicatechin (72 \u0026micro;g/g FW), with moderate quercetin (65 \u0026micro;g/g FW), high coumaric acid (326 \u0026micro;g/g FW), and lower rutin (25 \u0026micro;g/g FW). This variability underscores the diverse health benefits offered by different \u003cem\u003eFicus\u003c/em\u003e cultivars, highlighting the importance of cultivar-specific profiles in assessing their antioxidant and therapeutic potential. The unique profile of phenolic compounds in fruits varies by species and genotype, serving as a useful marker for chemotaxonomic classification. (Ou et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Gazdik et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Additionally, the polyphenolic content is influenced by the specific cultivar and its genetic composition (Matthes and Schmitz-Eiberger, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). The polyphenols identified in various \u003cem\u003eficus\u003c/em\u003e species in this study could contribute to the observed health benefits, as previous research has linked these flavanols to significant pharmacological effects (Matthes and Schmitz-Eiberger, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2012\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eData represents the variability of different bioactive molecules in ficus cultivars.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCultivar\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCatechin\u003c/p\u003e \u003cp\u003e(ug/gFW)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEpicatechin\u003c/p\u003e \u003cp\u003e(ug/gFW)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuercetin\u003c/p\u003e \u003cp\u003e(ug/gFW)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCoumaric acid\u003c/p\u003e \u003cp\u003e(ug/gFW)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRutin\u003c/p\u003e \u003cp\u003e(ug/gFW)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYL-G-01 Youngura Ganderbal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e94.00\u0026thinsp;\u0026plusmn;\u0026thinsp;33.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e72.00\u0026thinsp;\u0026plusmn;\u0026thinsp;14.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.00\u0026thinsp;\u0026plusmn;\u0026thinsp;31.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e326.00\u0026thinsp;\u0026plusmn;\u0026thinsp;44.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e25.00\u0026thinsp;\u0026plusmn;\u0026thinsp;14.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-G-14 Babawayil Gandebal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e63.00\u0026thinsp;\u0026plusmn;\u0026thinsp;45.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e58.00\u0026thinsp;\u0026plusmn;\u0026thinsp;18.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.00\u0026thinsp;\u0026plusmn;\u0026thinsp;17.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e241.00\u0026thinsp;\u0026plusmn;\u0026thinsp;40.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e38.00\u0026thinsp;\u0026plusmn;\u0026thinsp;13.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-G-04 Babawayil Gandebal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e56.00\u0026thinsp;\u0026plusmn;\u0026thinsp;53.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e72.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e127.00\u0026thinsp;\u0026plusmn;\u0026thinsp;28.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e36.00\u0026thinsp;\u0026plusmn;\u0026thinsp;11.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild \u0026minus;\u0026thinsp;01 Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e86.00\u0026thinsp;\u0026plusmn;\u0026thinsp;33.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e294.00\u0026thinsp;\u0026plusmn;\u0026thinsp;21.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e226.00\u0026thinsp;\u0026plusmn;\u0026thinsp;23.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e457.00\u0026thinsp;\u0026plusmn;\u0026thinsp;55.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e142.00\u0026thinsp;\u0026plusmn;\u0026thinsp;19.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDH-S-02 Dara Harwan Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e37.00\u0026thinsp;\u0026plusmn;\u0026thinsp;14.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e56.00\u0026thinsp;\u0026plusmn;\u0026thinsp;13.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.00\u0026thinsp;\u0026plusmn;\u0026thinsp;34.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e153.00\u0026thinsp;\u0026plusmn;\u0026thinsp;27.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e40.00\u0026thinsp;\u0026plusmn;\u0026thinsp;17.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS-S-06 Arabal Shalimar Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e153.00\u0026thinsp;\u0026plusmn;\u0026thinsp;22.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e65.00\u0026thinsp;\u0026plusmn;\u0026thinsp;23.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e181.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e86.00\u0026thinsp;\u0026plusmn;\u0026thinsp;11.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e31.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDH-S-08 Dara Harwan Srinagar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e26.00\u0026thinsp;\u0026plusmn;\u0026thinsp;11.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e67.00\u0026thinsp;\u0026plusmn;\u0026thinsp;13.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e314.00\u0026thinsp;\u0026plusmn;\u0026thinsp;27.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e12.00\u0026thinsp;\u0026plusmn;\u0026thinsp;9.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWild \u0026minus;\u0026thinsp;02 Ganderbal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e341.00\u0026thinsp;\u0026plusmn;\u0026thinsp;26.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e504.00\u0026thinsp;\u0026plusmn;\u0026thinsp;16.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e258.00\u0026thinsp;\u0026plusmn;\u0026thinsp;12.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e997.00\u0026thinsp;\u0026plusmn;\u0026thinsp;28.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e146.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe data is represented in mean SD\u0026plusmn; (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e\u003cem\u003eAcetyl cholinesterase, α- glucosidase and α- amylase inhibitory activity\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides detailed insights into the inhibitory potential of \u003cem\u003eficus\u003c/em\u003e fruit extracts against three key enzymes\u0026mdash;ACE (Angiotensin-Converting Enzyme), alpha-glucosidase, and alpha-amylase\u0026mdash;at a concentration of 100 \u0026micro;g/mL. This information is essential for comparing the potential of wild and cultivated \u003cem\u003eficus\u003c/em\u003e extracts in regulating Alzheimer\u0026rsquo;s disease and Diabetes. Wild \u0026minus;\u0026thinsp;02 Ganderbal is highlighted as the most effective cultivar in terms of enzyme inhibition. It demonstrates the highest ACE inhibitory activity at 87.13%, suggesting strong potential for managing Alzheimer\u0026rsquo;s disease (Kong et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Additionally, Wild \u0026minus;\u0026thinsp;02 exhibits substantial inhibition of alpha-glucosidase (85.59%) and alpha-amylase (90.71%), indicating its potential in controlling postprandial blood glucose levels by slowing carbohydrate digestion and absorption (Abdollahi et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). This comprehensive inhibitory profile positions Wild \u0026minus;\u0026thinsp;02 Ganderbal as a promising candidate for both Alzheimer\u0026rsquo;s disease and diabetes management, aligning with findings that effective enzyme inhibition can lead to better control of these conditions (Kumar et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Wild \u0026minus;\u0026thinsp;01 Srinagar also shows significant enzyme inhibitory activities. It showed an ACE inhibitory activity of 80.98%, Furthermore, its alpha-glucosidase (86.74%) and alpha-amylase (84.12%) inhibition levels suggest a strong capacity for controlling blood glucose levels, though slightly less effective than Wild \u0026minus;\u0026thinsp;02. Similar research supports that high alpha-glucosidase and alpha-amylase inhibition is associated with improved glycemic control, which is beneficial for diabetes management (Sreelatha \u0026amp; Padma, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). Among the cultivated \u003cem\u003eficus\u003c/em\u003e varieties AS-S-06 Arabal Shalimar Srinagar presents a balanced enzyme inhibitory profile with moderate ACE inhibition (62.33%), alpha-glucosidase inhibition (53.37%), and alpha-amylase inhibition (77.37%). DH-S-02 Dara Harwan Srinagar and DH-S-08 Dara Harwan Srinagar exhibit lower overall inhibitory activities. DH-S-08, with the lowest ACE inhibitory activity (25.03%) and relatively lower inhibition of alpha-amylase (66.57%), alongside moderate alpha-glucosidase inhibition (59.16%), indicates limited efficacy in managing both conditions. This supports findings that lower enzyme inhibition levels generally correspond to reduced therapeutic benefits (Lee et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). This variability underscores the diverse potential of \u003cem\u003eficus\u003c/em\u003e cultivars in addressing metabolic health conditions based on their enzyme inhibitory profiles.\u003c/p\u003e \n \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eAnticancer activity\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides a detailed illustration of the growth inhibition percentages exhibited by \u003cem\u003eFicus carica\u003c/em\u003e (commonly known as anjeer) fruit extracts when tested against various human cancer cell lines. The results underscore the significant anti-cancer potential of these fruit extracts. The findings highlight the differential anticancer efficacy of various \u003cem\u003eFicus carica\u003c/em\u003e cultivars. Specifically, the cultivar Wild-02 Ganderbal demonstrates potent growth inhibition, with notable inhibition rates of 85% in cervical (HeLa) cells, 89% in kidney (HEK) cells, 81% in lung (A-549) cells, 88% in prostate (PC-3) cells, and an exceptional 95% in breast (MCF-7) cells, indicating a broad-spectrum anticancer potential. Similarly, Wild-01 Srinagar exhibits significant inhibitory activity, particularly in breast (90%) and prostate (84%) cancer cell lines. In contrast, the B-G-04 Babawayil Ganderbal cultivar shows strong inhibition in kidney (79%) and prostate (73%) cells, while B-G-14 Babawayil Ganderbal presents moderate inhibition across most tested cell lines, with a peak inhibition of 81% in breast cancer cells. On the other hand, DH-S-02 Dara Harwan Srinagar reveals the lowest inhibition rates, particularly in cervical (17%) and prostate (19%) cells, indicating a markedly reduced efficacy against these cancer types. These observations underscore the variability in anticancer potency among different cultivars, with Wild varieties showing substantial promise for therapeutic application, particularly in breast and prostate cancers, while others exhibit more limited effects. The findings are corroborated by existing literature; research conducted by (Khan et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Kumar et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) has documented significant antioxidant activity and cytotoxic effects of anjeer extracts on various cancer cell lines, including MCF-7, supporting the hypothesis that the cultivars assessed may harbor similar bioactive compounds contributing to their anticancer effectiveness. Furthermore, Saha et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) highlighted the variability in cytotoxicity across different \u003cem\u003eFicus carica\u003c/em\u003e cultivars, consistent with the results presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Additionally, a comprehensive review by Ben Saad et al., 2020) underscores the presence of beneficial phytochemicals in \u003cem\u003eFicus carica\u003c/em\u003e that enhance its anticancer potential, aligning with the superior performance of Wild-02. Collectively, these results emphasize the critical need for evaluating wild anjeer cultivars to identify the most effective treatments for diverse cancer types. They also suggest avenues for further investigation into the underlying mechanisms of action and the potential for synergistic effects through combination therapies to enhance therapeutic efficacy.\u003c/p\u003e \n \u003cp\u003eThe higher content of bioactive compounds and enhanced therapeutic activities observed in wild varieties of plants compared to cultivated varieties, can be attributed to several key factors such as (a) \u003cem\u003eEnvironmental Stress Responses\u003c/em\u003e: Wild plants frequently encounter a diverse array of environmental stresses that significantly influence their physiological and biochemical processes. These stresses include extreme temperatures, drought, soil nutrient variability, and high levels of ultraviolet (UV) radiation. In response to these challenging conditions, wild plants often enhance their production of secondary metabolites, which play crucial roles in their survival and adaptation. Extreme temperatures, both high and low, can have profound effects on plant physiology. In high-temperature conditions, plants may experience increased oxidative stress due to higher levels of reactive oxygen species (ROS). To counteract this stress, plants often upregulate the synthesis of antioxidant secondary metabolites such as phenolic compounds, flavonoids, and carotenoids. These compounds help neutralize ROS and protect cellular components from oxidative damage. Conversely, low temperatures can induce the accumulation of cryoprotectants and other metabolites that prevent ice formation and cellular damage (Wang et al., 2011). (b) \u003cem\u003eGenetic diversity\u003c/em\u003e: Genetic diversity within plant populations plays a crucial role in determining the range and abundance of bioactive compounds they produce. Wild plant varieties typically exhibit higher genetic diversity compared to their cultivated counterparts. This variability stems from their exposure to a broad spectrum of environmental pressures and evolutionary forces, which continuously shape their genetic makeup. This genetic diversity enables wild plants to adapt to diverse and often challenging conditions by evolving a more extensive array of biochemical responses, including the production of secondary metabolites. (Degenhardt et al., 2009). (C) \u003cem\u003eSoil Composition\u003c/em\u003e: Soil and nutrient availability are critical factors influencing plant growth and biochemical composition. Wild plants, which often thrive in diverse and nutrient-poor soils, have evolved adaptive strategies to cope with these challenging conditions. In contrast, cultivated plants are typically grown in soils that are enriched and optimized for agricultural productivity. This difference in soil conditions significantly impacts the production of bioactive compounds, which are often elevated in wild plants as a response to less favorable soil environments (Li et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2015\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePrincipal Component Analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) biplot illustrates the distribution of various samples (plotted as dots) and their relationship with multiple variables (represented by arrows). The PCA biplot shows two dimensions: Dim1, which explains 60.6% of the variance, and Dim2, which accounts for 16.5% of the variance. Different samples are labeled based on locations like \"DH-S-08 Dara Harwan Srinagar\" and \"Wild-02 Ganderbal.\" The sample points are plotted across the biplot. Samples like \"DH-S-08 Dara Harwan Srinagar\" are positioned towards the upper left, while samples like \"Wild-01 Srinagar\" and \"Wild-02 Ganderbal\" are located on the right side, indicating varying characteristics. Overall, the biplot highlights the variation among the different samples concerning the measured biochemical or cellular properties. The first two principal components explain a large portion of the variance in the data, with the distribution of samples showing differing characteristics based on their positioning in relation to the key variables.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e is a correlation plot showing the relationship between multiple variables and principal components (PCs). Each cell in the matrix indicates the strength and direction of the correlation between a variable (rows) and a principal component (columns, labeled Dim1 to Dim7). The intensity of the color and size of the circles represent the magnitude of the correlation, with the color scale ranging from dark blue (strong positive correlation) to dark red (strong negative correlation). Phenols and FRAP have strong positive correlations with Dim1 (large blue circles), indicating these variables are highly associated with the first principal component. MCF7, PC3 and other cell line activities show moderate positive correlations with higher dimensions (e.g., Dim3, Dim4), with MCF7 having a strong positive correlation with Dim1. This plot provides insight into how each variable contributes to the variance captured by the different principal components, with Dim1 explaining a significant portion of the variance for several key variables such as phenolic content and antioxidant activity. The pattern of correlations helps to understand the underlying structure of the dataset.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Scree plot explained the percentage of variance associated with each principal component obtained by drawing a graph between eigen values and principal component numbers. Screen plot displays eigen values in descending order, highlighting the elbow point where the eigen values stabilize. This indicates which components are significant to retain. PCA1 accounts for 60.6% of the variance, while PCA2 explains 16.5%. The remaining components show decreasing variability, with PCA3 at 10.3%, PCA4 at 5.7%, PCA5 at 5%, PCA6 at 1.6%, PCA7 at 0.2%. The concentration of data in PCA1 suggests it has superior performance, as a higher percentage of retained data correlates with better overall data performance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study provides a comprehensive comparative analysis of wild and cultivated \u003cem\u003eFicus carica\u003c/em\u003e cultivars, highlighting the significant therapeutic potential of wild varieties. Among these, Wild-02 Ganderbal stands out as a promising candidate for future pharmaceutical or dietary supplement development due to its exceptional bioactive compound profile. The research confirms a strong correlation between high phenolic content and enhanced antioxidant activity, aligning with previous studies that emphasize the health benefits of polyphenols. However, a more comprehensive evaluation of the bioactivity of individual compounds, as well as their synergistic interactions, is essential. Further investigation into these compounds, particularly in the context of disease management, is necessary to assess their viability for commercialization as pharmaceutical agents or dietary supplements, thus contributing to advances in healthcare paradigms. While in vitro assays provide valuable preliminary insights into the therapeutic potential of fruit extracts, they do not fully replicate the complex interactions that occur in vivo. Therefore, future research should incorporate animal models to validate the anti-cancer and anti-diabetic effects observed in vitro. Additionally, a deeper investigation into the molecular mechanisms underlying these therapeutic effects is critical. This can be achieved through transcriptomic, proteomic and metabolomic analyses, which would elucidate how bioactive compounds derived from wild plants interact with biological systems to exert their effects. Understanding these mechanisms will be key to advancing the application of these compounds in therapeutic contexts.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eConflicts of interest:\u003c/h2\u003e \u003cp\u003eThe authors have no conflicts of interest to this work.\u003c/p\u003e \u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eZNS: Conceptualisation, Methodology, Data curation, Validation, Formal analysis, Investigation, Resources, Visualisation, Writing \u0026ndash; original draft; NS: Conceptualisation, Validation,Writing \u0026ndash; review and editing; VS: Validation, Writing \u0026ndash; review and editing, Supervision;PB:Validation, Writing \u0026ndash; review and editing, Supervision;SR: Conceptualisation, Validation,Writing \u0026ndash; review and editing; FSA: Investigation, Resources.All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgment:\u003c/h2\u003e \u003cp\u003eThis research work was funded by Institutional Fund Project under grant no. (RSPD2024R693). The authors gratefully acknowledge King Saud University, Riyadh, Saudi Arabia.\u003c/p\u003e\u003ch2\u003eData Availability Statement:\u003c/h2\u003e \u003cp\u003eThe data presented in this study are available on request from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAbdollahi M et al (2020) Alpha-glucosidase and alpha-amylase inhibitory activities of some medicinal plants used in Iran. J Ethnopharmacol 259:112941\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfshar FH, Delazar A, Nazemiyeh H et al (2019) Comparison of the total phenol, flavonoid contents and antioxidant activity of methanolic extracts of \u003cem\u003eArtemisia spicigera\u003c/em\u003e and \u003cem\u003eA. splendens\u003c/em\u003e growing in Iran. Pharm Sci 18(3):165\u0026ndash;170\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkin EB, Karabulut I, Topcu A (2008) Some compositional properties of main Malatya apricot (Prunus armeniaca L.) varieties. Food Chem 107(2):939\u0026ndash;948\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBors W, Michel C, Schikora S (1995) Interaction of flavonoids with ascorbate and determination of their univalent redox potentials: A pulse radiolysis study. Free Radic Biol Med 19(1):45\u0026ndash;52\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBors W, Saran M, Michel C (2008) Antioxidant properties of flavonoids and phenolic compounds. Free Radic Res 42(8):792\u0026ndash;804\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDegenhardt J, Harrison RRTWNPW (2009) R. W. Miller. Genetic variation and secondary metabolite production in wild and cultivated plants. J Agric Food Chem 57(9):3825\u0026ndash;3832\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDourado F, Van den Berg C, Gama M (2016) European Regulatory Framework on Novel Foods and Novel Food Additives. Bacterial Nanocellulose Biotechnol. Bio-Econ 8:135\u0026ndash;144\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaneshpurkar A, Saluja AK (2017) The pharmacological potential of rutin. Saudi Pharm J 25(2):149\u0026ndash;164\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGazdik Z, Reznicek V, Adam V, Zitka O, Jurikova T, Krska B, Matuskovic J, Plsek J, Saloun J, Horna A, Kizek R (2008) Use of Liquid Chromatography with Electrochemical Detection for the Determination of Antioxidants in Less Common Fruits. Molecules 13:2823\u0026ndash;2836\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarassi Y, Tilaoui M, Idir A et al (2019) Phytochemical analysis, cytotoxic and antioxidant activities of \u003cem\u003emyrtuscommunis\u003c/em\u003e essential oil from Morocco. \u003cem\u003eJournal of Complementary and Integrative Medicine\u003c/em\u003e, 16(3), 1\u0026ndash;8. in Chitrakadivati by UV-Spectrophotometer. AncSci Life. 31(4), 198\u0026ndash;201\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarav S, Eksi A (2012) Antioxidant capacity and total phenolic contents of peach and apricot cultivars harvested from different regions of turkey. Int J food Nutr Sci 4:13\u0026ndash;17\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaur C, Kapoor H, Ghosh A (2021) Antioxidant and phytochemical properties of medicinal plants. Phytother Res 35(4):1536\u0026ndash;1547\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaurinovic B, Vastag D (2019) Flavonoids and phenolic acids as potential natural antioxidants. Antioxidants. Intech Open, London UK, pp 1\u0026ndash;20\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan M, Riaz M, Ahmed N (2017) Assessment of antioxidant and phytochemical content of selected plant species. Int J Environ Res Public Health 14(9):1\u0026ndash;10\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong W et al (2016) ACE inhibition and antihypertensive effects of fruit and vegetable extracts. Food Chem 194:482\u0026ndash;489\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar R et al (2019) Effects of natural inhibitors on key metabolic enzymes. J Med Plants Res 13(5):70\u0026ndash;80\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar S et al (2018) Anti-cancer potential of Prunus armeniaca extracts and their underlying mechanisms. J Cancer Res Clin Oncol 144(8):1567\u0026ndash;1576\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwiatkowski P, Mnichowska-Polanowska M, Pruss A, Masiuk H, Dzi ˛ecioł M, Giedrys-Kalemba S, Sienkiewicz M (2017) The effect of fennel essential oil in combination with antibiotics on Staphylococcus aureus strains isolated from carriers. Burns 43:1544\u0026ndash;1551\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLai PK, Roy J (2004) Antimicrobial and chemopreventive properties of herbs and spices. Curr Med Chem 11(11):1451\u0026ndash;1460\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLai PK, Roy J (2004) Antimicrobial and chemopreventive properties of herbs and spices. Curr Med Chem 11(11):1451\u0026ndash;1460\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee YK et al (2014) Therapeutic potentials of enzyme inhibitors in managing chronic diseases. Front Pharmacol 5:70\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi X, Liu Y, Zhou Z (2015) Nutrient availability and its impact on secondary metabolite production in plants. Plant Physiol Biochem 89:77\u0026ndash;83\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang JY, Xu J, Yang YY, Shao YZ, Zhou F, Wang JL (2020) Toxicity and Synergistic Effect of Elsholtziaciliata Essential Oil and Its Main Components against the Adult and Larval Stages of Tribolium Castaneum. Foods 9:345\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatthes A, Schmitz-Eiberger M (2009) Apple (Malusdomestica L. Borkh.) allergen Mal d 1: effect of cultivar, cultivation system, and storage conditions. J Agric Food Chem 57(22):10548\u0026ndash;10553\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatthes A, Schmitz-Eiberger M (2012) Polyphenol content and antioxidant capacity of apple fruit: effect of cultivar and storage conditions. J Appl Bot Food Qual 82(2):152\u0026ndash;157\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohamed M, El A, Ashour AS, Sadek A, Melad G (2019) A review on saponins from medicinal plants: chemistry, isolation, and determination. 7(4):282\u0026ndash;288\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlimpia A, Alexa E, Lalescu D, Berbecea A, Camen D, Mariana P, Moigradean A, D., \u0026amp;, Bala M (2018) Chemical composition and antioxidant activity of some apricot varieties at different ripening stages. Chil J agricultural Res 78(2):266\u0026ndash;275\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOu BX, Huang DJ, Hampsch-Woodill M, Flanagan JA, Deemer EK (2002) Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: A comparative study. J Agric Food Chem 50:3122\u0026ndash;3128\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOu BX, Huang DJ, Hampsch-Woodill M, Flanagan JA, Deemer EK (2002) Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: A comparative study. J Agric Food Chem 50:3122\u0026ndash;3128\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev 2(5):270\u0026ndash;278\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePellegrini M, Ricci A, Serio A, Chaves-L\u0026oacute;pez C, Mazzarrino G, D\u0026rsquo;Amato S, Sterzo L, C., \u0026amp;, Paparella A (2018) Characterization of Essential Oils Obtained from Abruzzo Autochthonous Plants, vol 7. Antioxidant and Antimicrobial Activities Assessment for Food Application. Foods, p 19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoverenov E, Plumb NS, Anderson LD (2014) Secondary metabolite production in wild versus cultivated plants: A comparative study. Planta 240.2 : 405\u0026ndash;418\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRice-Evans CA, Miller NJ, Paganga G (1996) Structure antioxidant activity relationship of flavonoids and phenolic acids. Free Radical Biol Med 20:933\u0026ndash;956\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuvanthika PN, \u0026amp;Manikandan SA (2019) Study on antioxidant activity, phenol, and flavonoid content of seedpod of Nelum bonucifera Gaertn. Drug Invent Today 11(4):835\u0026ndash;840\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaha P, Talukdar AD, Nath R, Sarker SD, Nahar L, Sahu J, Choudhury MD (2019) Role of natural phenolics in hepatoprotection: a mechanistic review and analysis of regulatory network of associated genes. Front Pharmacol 10:509\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh P, Singh G, Bhandawat A, Singh G, Parmar R, Seth R, Sharma RK (2017) Spatial transcriptome analysis provides insights of key gene(s) involved in steroidal saponin\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSreelatha S, Padma PR (2009) Antioxidant and enzyme inhibitory activities of Prunus armeniaca. J Food Sci 74(7):H227\u0026ndash;H233\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun B, Wang J (2017) Food additives. In Food Safety in China. Part 3 Food Chemistry. In Food Additives; Jean, J.J., Chen, J., Eds.; John Wiley \u0026amp; Sons: Hoboken, NJ, USA, pp. 185\u0026ndash;200\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUniyal SK, Singh KN, Jamwal P, Lal B (2006) Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya. J Ethnobiol Ethnomed 2:1\u0026ndash;8\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Z, Zhang L, Zeng X (2008) Selective breeding effects on secondary metabolite levels in cultivated plants. Front Plant Sci 9:465\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei G, Yang F, Wei F, Zhang L, Gao Y, Qian J, Chen Z, Jia Z, Wang Y, Su H, Dong L, Xu J, Chen S (2020) Metabolomes and transcriptomes revealed the saponin distribution in root tissues of Panaxquinque folius and Panaxnotoginseng. J Ginseng Res 44(6):757\u0026ndash;769. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jgr.2019.05.009\u003c/span\u003e\u003cspan address=\"10.1016/j.jgr.2019.05.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Antibiotics, Bioactive compounds, anti-diabetic, anti-Alzheimer, and anti-cancer","lastPublishedDoi":"10.21203/rs.3.rs-5334005/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5334005/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe growing resistance to conventional antibiotics has spurred the need for alternative therapies, underscoring the significance of investigating medicinal plants for novel bioactive compounds. This study focuses on comparative qualitative and quantitative biochemical analysis, alongside an evaluation of the in vitro anti-diabetic, anti-Alzheimer, and anti-cancer properties of different wild and cultivated \u003cem\u003eFicus carica\u003c/em\u003e cultivars. HPLC analysis was conducted to measure the content of bioactive compounds among the wild and cultivated \u003cem\u003eficus\u003c/em\u003e accessions. The extracts were subsequently evaluated for their therapeutic potential against several human cancer cell lines, including prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), cervical cancer (HELA) and kidney cancer (HEK). This analysis highlighted distinct genetic similarities and differences among the \u003cem\u003eficus\u003c/em\u003e cultivars. Comprehensive statistical analyses were employed to discern patterns and relationships among various\u003cem\u003e ficus\u003c/em\u003e cultivars. This research marks the first comprehensive examination of the phytochemical screening of wild and cultivated accessions of \u003cem\u003eficus ciraca\u003c/em\u003e. Among the cultivars examined, the wild varieties exhibited the highest concentrations of bioactive compounds and demonstrated the most significant health benefits. The results of this study provide a solid scientific basis for the future isolation and purification of therapeutic compounds in wild fruits, potentially leading to their application in pharmaceuticals or dietary supplements. This research will greatly enhance our understanding of the pharmacological properties of wild \u003cem\u003eficus\u003c/em\u003e fruits and establishes a basis for further investigation into their clinical benefits\u003c/p\u003e","manuscriptTitle":"Comparative Analysis of Bioactive Compounds and Health Benefits of Wild and Cultivated Ficus carica Accessions from the Northern Himalayas","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-06 18:03:47","doi":"10.21203/rs.3.rs-5334005/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16726736-8856-4fbf-8f4b-78d97b3564d2","owner":[],"postedDate":"November 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-08T17:23:33+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-06 18:03:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5334005","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5334005","identity":"rs-5334005","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}