Consolidation of network and experimental pharmacology to divulge the antidiabetic action of L. bark.

UNLABELLED

A total of 21 different bioactives were identified from in which 3 molecules, i.e., apigenin, 3',4',5,7-tetrahydroxy-3-methoxyflavone, and kaempferol were predicted to target the highest number of proteins involved in diabetic pathogenesis in which protein tyrosine phosphatase 1b was primarily targeted. Similarly, a docking study identified ursolic acid to have the highest binding affinity with protein tyrosine phosphatase 1b. The combined synergic network analysis identified PI3K/Akt signaling pathway to be primarily modulated followed by the calcium signaling pathway. Similarly, in oral glucose tolerance test, we observed the efficacy of hydroalcoholic extract of to lower the total area under the curve of glucose and increase total area under curve of insulin for 2 hours. Likewise, hydroalcoholic extract reversed the altered homeostatic hepatic enzymes after 28 days of treatments. Similarly, the extract also enhanced the antioxidant enzymes level like catalase and superoxide dismutase in liver homogenate. In summary, hydroalcoholic extract of bark may act as an antidiabetic agent by enhancing the glycolysis, decreasing gluconeogenesis, promoting glucose uptake, enhancing insulin secretion, and maintaining pancreatic β-cell mass via PI3K/Akt signaling pathway and downregulating the function of  protein tyrosine phosphatase 1b.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s13205-021-02788-7.