Network and experimental pharmacology to decode the antihyperglycemic action of selected ethnobotanicals

Abstract

Background: Curcuma longa, Emblica officinalis, Momordica charantia, Pterocarpus marsupium, Salacia chinensis, and Tinospora cordifolia are ethnobotanicals with antidiabetic properties. Nevertheless, the effect of these plants when used together against diabetes is unestablished. Therefore, this study investigates the combined action of above-mentioned medicinal plants using network and experimental pharmacology. Methods: In network pharmacology module, compound of all six plants were evaluated for drug-likeness, and their corresponding targets were identified and subjected to enrichment analysis. Additional experiment was conducted using a high-fat diet, low-dose streptozotocin-induced diabetic model. Furthermore, in vitro α-amylase and α-glucosidase enzyme inhibition assays were performed. Results: Among all compounds evaluated, (S)-tembetarine from E. officinalis showed highest drug-likeness score of 1.2. Likewise, enrichment analysis of identified targets revealed distinct cellular components, biological processes, and molecular functions. Molecular docking further showed that Lobatoside I from M. charantia exhibited strongest binding affinity toward α-amylase, with a docking score of -15.587, while (−)-(3S)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-hepten-3-ol from C. longa showed strongest binding affinity toward α-glucosidase, with a score of -9.284. Subsequent experimental pharmacology demonstrated that combined extract of these ethnobotanicals effectively reduced hyperglycemia by restoring glucose homeostasis, as confirmed by oral glucose tolerance test and insulin tolerance test. Combined extract also improved lipid metabolism and glycogenesis. Moreover, α-amylase and α-glucosidase enzymes were inhibited by extract in concentration-dependent. Bodyweight showed a gradual increase alongside a reduction in food intake. Additionally, after 18 days of treatment, there was decline in nitrogen metabolites, ameliorated lipid profile, and hepatic glycogen content. Conclusion: This study established notable antidiabetic effects of selected ethnobotanicals through improved glucose homeostasis, inhibition of α-amylase and α-glucosidase enzymes, and amelioration of metabolic abnormalities via multi-target mechanisms.