Oleanolic acid (pentacyclic triterpenes) as a potential candidate for α-glycosidase inhibition activity

Shabnam Javed, Iqra Javaid, Amna Shoaib, Shagufta Perveen


Background: Diabetes mellitus is a common health dilemma worldwide and is characterized by hyperglycemia. Inhibition in the activity of one of the digestive tract enzymes α-glucosidase is one of the therapeutic approaches to hydrolyze carbohydrates into glucose using natural agents. Many natural compounds with α-glucosidase inhibitory activity have transpired to be secondary metabolites. Monotheca buxifolia, native to Pakistan is a major medicinal tree, which has been known for its extensive pharmacological activities.

Methods: α-glucosidase activity of ten isolated compounds (lupeol, lupeol acetate, betulin, β-sitosterol, β-amyrin, oleanolic acid, vanillic acid, protocatechuic acid, kaempferol and quercetin) from lipophilic hexane fraction of M. buxifolia (stem and leaves) was assessed against α-glucosidase enzyme using acarbose as a control.

Results: All ten compounds hold α-glucosidase inhibition potential (91-99%). However, IC50 (half-maximal inhibitory concentration) values of oleanolic acid (5 µM) were 8-fold lower than that of acarbose. Moreover, inhibition potencies of lupeol (15.87 µM), β-amyrin (18.14 µM) betulin (21.49 µM), quercetin (23.47 µM), and lupeol acetate (29.45 µM) were much stronger than the inhibitory effect obtained from acarbose (38.25 µM).

Conclusion: Oleanolic acid of M. buxifolia exhibited a potent inhibitory effect against α-glucosidase, therefore, oleanolic acid may be utilized in medicinal formulations against diabetic disorders.

Keywords: Diabetes mellitus; Enzyme inhibition; Medicinal plants; Pentacyclic triterpenes 

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Riddle MC. Standards of medical care in diabetes. Standards of medical care in diabetes. American Diabetes Association, (2019); 42: S1-S193.

Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmond M. Complications of diabetes. Journal of Diabetes Research, (2017); Article ID 3086167.

Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: a 21st century challenge. The lancet Diabetes & Endocrinology, (2014); 2: 56-64.

Konda YP, Egi JY, Dasari S, Katepogu R, Jaiswal KK, et al. Ameliorative effects of Mentha aquatica on diabetic and nephroprotective potential activities in STZ-induced renal injury. Comparative Clinical Pathology, (2020); 29(1): 189-99.

ReMukesh R, Namita P. Medicinal plants with antidiabetic potential-A review. American-Eurasian Journal of Agricultural & Environmental Sciences, (2017); 13: 9481-94.

Ayele, AG, Kumar P, Engidawork E. Antihyperglycemic and hypoglycemic activities of the aqueous leaf extract of Rubus Erlangeri Engl (Rosacea) in mice. Metabolism Open, (2021); 11: Article ID 100118.

Van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, De Grauw WJ. Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose. Cochrane Database of Systematic Reviews, (2006); 18: CD005061.

Li T, Zhang XD, Song YW. A microplate-based screening method for alpha-glucosidase inhibitors. The Chinese Journal of Clinical Pharmacology, (2005); 10: 1128-1134.

Ali JS, Saleem H, Mannan A, Zengin G, Mahomoodally MF, et al. Metabolic fingerprinting, antioxidant characterization, and enzyme-inhibitory response of Monotheca buxifolia (Falc.) A. DC. extracts. BMC Complementary Medicine and Therapies, (2020); 20(1): 313.

Yin Z, Zhang W, Feng F, Zhang Y, Kang W. α-Glucosidase inhibitors isolated from medicinal plants. Food Science and Human Wellness, (2014); 3: 136-74.

Javed S, Mahmood Z, Khan KM, Sarker SD, Javaid A, et al. Lupeol acetate as a potent antifungal compound against opportunistic human and phytopathogenic mold Macrophomina phaseolina. Scientific Reports, (2021); 11, Article number: 8417.

Javed S, Shoaib A, Mehmood Z, Nawaz S, Khan KM. Phytochemical, pharmacological and GC-MS characterization of the lipophilic fraction of Monotheca buxifolia. Asian Journal of Agriculture and Biology, (2021); 3: 1-7

Javed S, Shoaib A, Mehmood Z, Nawaz S. Hepatoprotective effect of methanolic extract of Monotheca buxifolia against isoniazid and rifampicin induced hepatotoxicity. Asian Journal of Agriculture and Biology, (2021); 4: 1-6.

Mazura P, Susanti D, Rasadah MA. Antiinflammatory action of components from Melastoma malabathricum. Pharmaceutical Biology, (2007); 45(5): 372-375.

Zhang BW, Xing Y, Wen C, Yu XX, Sun WL, et al. Pentacyclic triterpenes as α-glucosidase and α-amylase inhibitors: structure-activity relationships and the synergism with acarbose. Bioorganic & Medicinal Chemistry Letters, (2017); 27: 5065-70.

Nguyen NH, Pham DD, Le TT, Nguyen TA, Huynh DL, et al. Synthesis and α-Glucosidase inhibitory activity of ursolic acid, lupeol, and betulinic acid derivatives. Chemistry of Natural Compounds, (2021); 57: 1038-41.

Phan HV, Duong TH, Pham DD, Pham HA, Nguyen VK, et al. Design and synthesis of new lupeol derivatives and their α-glucosidase inhibitory and cytotoxic activities. Natural Product Research, (2022); 36(1): 1-7.

Liu S, Yu Z, Zhu H, Zhang W, Chen Y. In vitro α-glucosidase inhibitory activity of isolated fractions from water extract of Qingzhuan dark tea. BMC Complementary and Alternative Medicine, (2016); 16: 378.

Bhatia A, Singh B, Arora R, Arora S. In vitro evaluation of the α-glucosidase inhibitory potential of methanolic extracts of traditionally used antidiabetic plants. BMC Complementary and Alternative Medicine, (2019); 9: 1-9.

Thengyai S, Thiantongin P, Sontimuang C, Ovatlarnporn C, Puttarak P. α-Glucosidase and α-amylase inhibitory activities of medicinal plants in Thai antidiabetic recipes and bioactive compounds from Vitex glabrata R. Br. stem bark. Journal of Herbal Medicine, (2020); 19: 100302.

Lee D, Park JY, Lee S, Kang KS. In vitro studies to assess the α-glucosidase inhibitory activity and insulin secretion effect of isorhamnetin 3-o-glucoside and quercetin 3-o-glucoside isolated from Salicornia herbacea. Processes, (2021); 9: 483.

Deng XY, Ke JJ, Zheng YY, Li DL, Zhang K, et al. Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, (2022); 37: 451-461.

Dubey VK, Patil CR, Kamble SM, Tidke PS, Patil KR, et al. Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats. Journal of Pharmacology and Pharmacotherapeutics, (2013); 4(1): 47.

Gao D, Li Q, Li Y, Liu Z, Fan Y, Han Z, et al. Antidiabetic potential of oleanolic acid from Ligustrum lucidum Ait. Canadian Journal of Physiology and Pharmacology, (2007); 85: 1076-83.

Teodoro T, Zhang L, Alexander T, Yue J, Vranic M, et al. Oleanolic acid enhances insulin secretion in pancreatic β-cells. FEBS Letters, (2008); 582: 1375-80.

Malik A, Jamil U, Butt TT, Waquar S, Gan SH, et al. In silico and in vitro studies of lupeol and iso-orientin as potential antidiabetic agents in a rat model. Drug Design, Development and Therapy, (2019); 13: 1501-1513.

Lakshmi V, Mahdi AA, Ahmad MK, Agarwal SK, Srivastava AK. Antidiabetic activity of lupeol and lupeol esters in streptozotocin-induced diabetic rats. Bangladesh Pharmaceutical Journal, (2014); 17: 138-46.

Beserra FP, Vieira AJ, Gushiken LF, de Souza EO, Hussni MF, et al. Lupeol, a dietary triterpene, enhances wound healing in streptozotocin-induced hyperglycemic rats with modulatory effects on inflammation, oxidative stress, and angiogenesis. Oxidative Medicine and Cellular longevity, 2019; Article ID 3182627.

Song TJ, Park CH, In KR, Kim JB, Kim JH, et al. Antidiabetic effects of betulinic acid mediated by the activation of the AMP-activated protein kinase pathway. PLoS One, (2021); 16: e0249109.

Eid MH, Haddad S P. The antidiabetic potential of quercetin: underlying mechanisms. Current Medicinal Chemistry, (2017); 1: 24: 355-64.


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