Antidiabetic potential and phytochemical profiling of leea indica young leaves using LC-MS/MS
Keywords:
Diabetes Mellitus, Leea indica, Antioxidant, LC-MS/MS, Antidiabetic agents.
Abstract
Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, affecting millions worldwide. Leea indica, a medicinal plant native to tropical Asia, has been traditionally used to treat various ailments, including diabetes. This study aimed to investigate the antioxidant, α-glucosidase, and α-amylase inhibitory activities of L. indica leaves ethanol extract and identify its bioactive compounds using LC-MS/MS. The extract was prepared using maceration with 96% ethanol, yielding an extraction efficiency of 3.52%. Phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, tannins, quinones, and steroids/triterpenoids. The extract exhibited strong antioxidant activity (IC50 = 18.691 ± 0.05 µg/mL) and high total phenolic (6.957 ± 0.09 g GAE/100 g) and flavonoid (32.917 ± 0.07 g QE/100 g) contents. It also demonstrated potent α-glucosidase (IC50 = 7.90 µg/mL) and α-amylase (IC50 = 30,663.89 µg/mL) inhibitory activities. LC-MS/MS analysis identified 11 bioactive compounds, including phenylacetic acid (60.89%), shikimate (10.89%), kaempferol (3.67%), and quercetin (2.27%). These findings support the traditional use of L. indica in diabetes management and highlight its potential as a source of natural antidiabetic agents. Further in vivo studies and toxicity tests are necessary to confirm its efficacy and safety for human use.
References
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Mishra, G., Khosa, R. L., Tahseen, M. A., & Singh, P. (2016). Ethnobotany and phytopharmacology of Leea indica: An overview. Journal of Coastal Life Medicine, 4(1), 69–72. https://doi.org/10.12980/jclm.4.2016jclm-2014-0017
Nie, T., & Cooper, G. J. (2021). Mechanisms underlying the antidiabetic activities of polyphenolic compounds: A review. Frontiers in Pharmacology, 12, 798329. https://doi.org/10.3389/fphar.2021.798329
Op De Beck, P., Cartier, G., Dijoux‐Franca, M., David, B., & Mariotte, A. (2003). Antioxidant flavonoids and phenolic acids from leaves of Leea guineense G Don (Leeaceae). Phytotherapy Research, 17(4), 345–347. https://doi.org/10.1002/ptr.1141
Rahman, M. A., bin Imran, T., & Islam, S. (2013). Antioxidative, antimicrobial and cytotoxic effects of the phenolics of Leea indica leaf extract. Saudi journal of biological sciences, 20(3), 213-225. https://doi.org/10.1016/j.sjbs.2012.11.007
Rajsfus, B. F., Mohana-Borges, R., & Allonso, D. (2023). Diabetogenic viruses: linking viruses to diabetes mellitus. Heliyon, 9(4), e15021. https://doi.org/10.1016/j.heliyon.2023.e15021
Shamsudin, N. F., Ahmed, Q. U., Mahmood, S., Shah, S. A. A., Sarian, M. N., Khattak, M. M. A. K., ... & Latip, J. (2022). Flavonoids as antidiabetic and anti-inflammatory agents: A review on structural activity relationship-based studies and meta-analysis. International journal of molecular sciences, 23(20), 12605. https://doi.org/10.3390/ijms232012605
Shanmugam, S., Baby, J. P., Chandran, R., Thankarajan, S., & Thangaraj, P. (2016). Maesa indica: a nutritional wild berry rich in polyphenols with special attention to radical scavenging and inhibition of key enzymes, α-amylase and α-glucosidase. Journal of food science and technology, 53, 2957-2965. https://doi.org/10.1007/s13197-016-2263-3
Singh Grewal, A., Lather, V., Pandita, D., & Bhayana, G. (2017). Synthesis, Docking and Evaluation of Phenylacetic Acid and Trifluoro-methylphenyl Substituted Benzamide Derivatives as Potential PPARδ Agonists. Letters in Drug Design & Discovery, 14(11), 1239-1251. https://doi.org/10.2174/1570180814666170327164443
Srinivasan, G., Vijayan, K., & Ranjith, C. (2008). Identification of chemical compounds from the leaves of Leea indica. Acta Pharmaceutica, 58(2). https://doi.org/10.2478/v10007-008-0002-7
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Tsutsui, H., Kondo, K., & Tanaka, G. (2020). Diabetes Mellitus (pp. 73–86). springer singapore. https://doi.org/10.1007/978-981-15-1831-7_8
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Wong, Y. H., & Abdul Kadir, H. (2011). Induction of Mitochondria-Mediated Apoptosis in Ca Ski Human Cervical Cancer Cells Triggered by Mollic Acid Arabinoside Isolated fromLeea indica. Evidence-Based Complementary and Alternative Medicine, 2012(6835), 1–11. https://doi.org/10.1155/2012/684740
Wong, Y. H., Ling, S. K., & Abdul Kadir, H. (2011). Bioassay-Guided Isolation of Cytotoxic Cycloartane Triterpenoid Glycosides from the Traditionally Used Medicinal PlantLeea indica. Evidence-Based Complementary and Alternative Medicine, 2012(2), 1–11. https://doi.org/10.1155/2012/164689
Zhang, Y. Y., Hou, L. Q., & Zhao, T. Y. (2014). Effects of acarbose on polycystic ovary syndrome: a meta-analysis. Experimental and Clinical Endocrinology & Diabetes, 122(06), 373-378. https://doi.org/10.1055/s-0034-1375676
Ar, S., & Padyana, S. (2022b). PHYSICOCHEMICAL AND PHYTOCHEMICAL EVALUATION OF LEEA INDICA (BURM.F.) MERR. International Journal of Research in Ayurveda and Pharmacy, 13(6), 66–70. https://doi.org/10.7897/2277-4343.1306158
Arivo, D., Rusmana, I., Batubara, I., & Mubarik, N. R. (2023). Antioxidant activity of various solvent extracts from endophytic bacteria isolated from girang (Leea indica) leaves. Biodiversitas Journal of Biological Diversity, 24(1). https://doi.org/10.13057/biodiv/d240148
Bodke, H., Wagh, V., & Kakar, G. (2023). Diabetes Mellitus and Prevalence of Other Comorbid Conditions: A Systematic Review. Cureus, 15(11). https://doi.org/10.7759/cureus.49374
Chua, L. S., Abd Wahab, N. S., & Soo, J. (2023). Water soluble phenolics, flavonoids and anthocyanins extracted from jaboticaba berries using maceration with ultrasonic pretreatment. Food Chemistry Advances, 3, 100387. https://doi.org/10.1016/j.focha.2023.100387
Dalu, D., & Dhulipala, S. (2016). Evaluation of possible mechanisms of three plants for blood glucose control in diabetes. ||| Bangladesh Journal of Pharmacology|||, 11(1), 224-230. https://doi.org/10.3329/bjp.v11i1.24932
Dalu, D., Duggirala, S., & Akarapu, S. (2014). Anti-hyperglycemic and hypolipidemic activity of Leea indica. Int. J. Bioassays, 3(7), 3155-3159.
Dalu, D., Duggirala, S., & Akarapu, S. (2019). Anti-hyperglycemic and hypolipidemic activity of Leea indica. International Journal of Bioassays, 3(07), 3155–3159. https://doi.org/10.21746/ijbio.2014.07.009
Etsassala, N. G., Badmus, J. A., Marnewick, J. L., Iwuoha, E. I., Nchu, F., & Hussein, A. A. (2020). Alpha-glucosidase and alpha-amylase inhibitory activities, molecular docking, and antioxidant capacities of Salvia aurita constituents. Antioxidants, 9(11), 1149
Juanda, D., Fidrianny, I., Wirasutisna, K. R., & Insanu, M. (2021). Evaluation of xanthine oxidase inhibitory and antioxidant activities of three organs of idat (Cratoxylum glaucum Korth.) and correlation with phytochemical cont. Pharmacognosy Journal, 13(4).
Jumina, J., Siswanta, D., Zulkarnain, A. K., Triono, S., Priatmoko, P., Yuanita, E., ... & Nursalim, I. (2019). Development of C-arylcalix [4] resorcinarenes and C-arylcalix [4] pyrogallolarenes as antioxidant and UV-B protector. Indonesian Journal of Chemistry, 19(2), 273-284. https://doi.org/10.22146/ijc.26868
Kanter, J. E., & Bornfeldt, K. E. (2016). Impact of Diabetes Mellitus. Arteriosclerosis, Thrombosis, and Vascular Biology, 36(6), 1049–1053. https://doi.org/10.1161/atvbaha.116.307302
Kosuge, T., & Sanger, M. (1986). Indoleacetic Acid, its Synthesis and Regulation: A Basis for Tumorigenicity in Plant Disease (pp. 147–161). springer us. https://doi.org/10.1007/978-1-4684-8056-6_6
Kottahachchi, D., Azam Mansoor, M., Maddumage, R., & Perera, E. (2021). Oxidative Stress in Type 2 Diabetes Mellitus – A Key Factor for Major Complications. International Journal of Research Publications, 70(1). https://doi.org/10.47119/ijrp100701220211740
Liebelt, D. J., Jordan, J. T., & Doherty, C. J. (2019) Only a matter of time: The impact of daily and seasonal rhythms on phytochemicals. Phytochemistry Reviews, 18, 1409-1433. https://doi.org/10.1007/s11101-019-09617-z
Margna, U., Vainjärv, T., & Laanest, L. (1989). Different l-phenylalanine pools available for the biosynthesis of phenolics in buckwheat seedling tissues. Phytochemistry, 28(2), 469–475.https://doi.org/10.1016/0031-9422(89)80034-2
Markert, C., Thinius, M., Lehmann, L., Heintz, C., Stappert, F., Wissdorf, W., ... & Covey, T. R. (2021). Observation of charged droplets from electrospray ionization (ESI) plumes in API mass spectrometers. Analytical and bioanalytical chemistry, 413, 5587-5600
Mishra, G., Khosa, R. L., Tahseen, M. A., & Singh, P. (2016). Ethnobotany and phytopharmacology of Leea indica: An overview. Journal of Coastal Life Medicine, 4(1), 69–72. https://doi.org/10.12980/jclm.4.2016jclm-2014-0017
Mishra, G., Khosa, R. L., Tahseen, M. A., & Singh, P. (2016). Ethnobotany and phytopharmacology of Leea indica: An overview. Journal of Coastal Life Medicine, 4(1), 69–72. https://doi.org/10.12980/jclm.4.2016jclm-2014-0017
Nie, T., & Cooper, G. J. (2021). Mechanisms underlying the antidiabetic activities of polyphenolic compounds: A review. Frontiers in Pharmacology, 12, 798329. https://doi.org/10.3389/fphar.2021.798329
Op De Beck, P., Cartier, G., Dijoux‐Franca, M., David, B., & Mariotte, A. (2003). Antioxidant flavonoids and phenolic acids from leaves of Leea guineense G Don (Leeaceae). Phytotherapy Research, 17(4), 345–347. https://doi.org/10.1002/ptr.1141
Rahman, M. A., bin Imran, T., & Islam, S. (2013). Antioxidative, antimicrobial and cytotoxic effects of the phenolics of Leea indica leaf extract. Saudi journal of biological sciences, 20(3), 213-225. https://doi.org/10.1016/j.sjbs.2012.11.007
Rajsfus, B. F., Mohana-Borges, R., & Allonso, D. (2023). Diabetogenic viruses: linking viruses to diabetes mellitus. Heliyon, 9(4), e15021. https://doi.org/10.1016/j.heliyon.2023.e15021
Shamsudin, N. F., Ahmed, Q. U., Mahmood, S., Shah, S. A. A., Sarian, M. N., Khattak, M. M. A. K., ... & Latip, J. (2022). Flavonoids as antidiabetic and anti-inflammatory agents: A review on structural activity relationship-based studies and meta-analysis. International journal of molecular sciences, 23(20), 12605. https://doi.org/10.3390/ijms232012605
Shanmugam, S., Baby, J. P., Chandran, R., Thankarajan, S., & Thangaraj, P. (2016). Maesa indica: a nutritional wild berry rich in polyphenols with special attention to radical scavenging and inhibition of key enzymes, α-amylase and α-glucosidase. Journal of food science and technology, 53, 2957-2965. https://doi.org/10.1007/s13197-016-2263-3
Singh Grewal, A., Lather, V., Pandita, D., & Bhayana, G. (2017). Synthesis, Docking and Evaluation of Phenylacetic Acid and Trifluoro-methylphenyl Substituted Benzamide Derivatives as Potential PPARδ Agonists. Letters in Drug Design & Discovery, 14(11), 1239-1251. https://doi.org/10.2174/1570180814666170327164443
Srinivasan, G., Vijayan, K., & Ranjith, C. (2008). Identification of chemical compounds from the leaves of Leea indica. Acta Pharmaceutica, 58(2). https://doi.org/10.2478/v10007-008-0002-7
Sun, C., Zhao, C., Guven, E. C., Paoli, P., Simal‐Gandara, J., Ramkumar, K. M., ... & Xiao, J. (2020). Dietary polyphenols as antidiabetic agents: Advances and opportunities. Food Frontiers, 1(1), 18-44. https://doi.org/10.1002/fft2.15
Tsutsui, H., Kondo, K., & Tanaka, G. (2020). Diabetes Mellitus (pp. 73–86). springer singapore. https://doi.org/10.1007/978-981-15-1831-7_8
Widyawati, P. S., Budianta, T. D. W., Kusuma, F. A., & Wijaya, E. L. (2014). Difference of solvent polarity to phytochemical content and antioxidant activity of Pluchea indicia less leaves extracts. International Journal of Pharmacognosy and Phytochemical Research, 6(4), 850-855. https://repository.ukwms.ac.id/id/eprint/10684/
Wong, Y. H., & Abdul Kadir, H. (2011). Induction of Mitochondria-Mediated Apoptosis in Ca Ski Human Cervical Cancer Cells Triggered by Mollic Acid Arabinoside Isolated fromLeea indica. Evidence-Based Complementary and Alternative Medicine, 2012(6835), 1–11. https://doi.org/10.1155/2012/684740
Wong, Y. H., Ling, S. K., & Abdul Kadir, H. (2011). Bioassay-Guided Isolation of Cytotoxic Cycloartane Triterpenoid Glycosides from the Traditionally Used Medicinal PlantLeea indica. Evidence-Based Complementary and Alternative Medicine, 2012(2), 1–11. https://doi.org/10.1155/2012/164689
Zhang, Y. Y., Hou, L. Q., & Zhao, T. Y. (2014). Effects of acarbose on polycystic ovary syndrome: a meta-analysis. Experimental and Clinical Endocrinology & Diabetes, 122(06), 373-378. https://doi.org/10.1055/s-0034-1375676
Published
2025-07-15
How to Cite
Sodik, J. J., & Sutrisno, E. (2025). Antidiabetic potential and phytochemical profiling of leea indica young leaves using LC-MS/MS. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.17849
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Research Article
