Exploring anti-diabetic activity of Caryota mitis Lour. through modulation of PPAR- α/γ, GLUT-4, using in-vitro, in-vivo and in-silico approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Caryota mitis Lour. has been used as a folk remedy to cure hyperglycemia in Thailand and Bangladesh.

AIM OF THE STUDY: This study aims to explore the effect of the methanol extract of C. mitis stem on high-fat diet streptozotocin-induced diabetes in rats.

MATERIAL AND

METHODS

This study firstly analyzed the active phytoconstituents of methanol extract of C. mitis using HR-LCMS-QTOF, then a series of in-vitro investigations, including MTT assay, enzymatic assay, glucose uptake assay, and gene expression study using HepG2 cell model, was performed. Then, in-vivo investigations were performed on the STZ-induced HFD type 2 diabetes mellitus (TIIDM) rat model, which included an assessment of acute toxicity, body weight, biochemical tests, and histopathological evaluation. Furthermore, an in-silico study was performed using AUTODOCK Tools 1.5.6 and BIOVIA Discovery Studio 4.0, then a molecular dynamics (MD) simulation was performed for 100 ns for the best compounds using Desmond.

RESULTS

Our results reveal that methanol extract C. mitis (MECM) has no toxic effect in-vitro and in-vivo models. The MECM inhibited the α-glucosidase and α-amylase in a dose-dependent manner. Moreover, the MECM improves glucose uptake and normalizes GLUT-4, PPAR-α, and PPAR-γ expression in HepG2 cells. Furthermore, MECM treatment improved oral glucose tolerance and showed anti-hyperglycemia activity in HFD-STZ diabetic rats. The molecular docking and MD simulation results reveal that Sciadopitysin and Catechin of MECM are the desirable compounds for anti-hyperglycemia activity.

CONCLUSION

The results suggest that C. mitis significantly reduces blood glucose levels through the PPAR- α/γ, GLUT-4, and is a promising natural antidiabetic agent.