Network pharmacology-based elucidation of bioactive compounds and experimental exploration of antidiabetic mechanisms of Hydrolea zeylanica

Abstract

This investigation systematically explored the underlying antidiabetic mechanism of Hydrolea zeylanica (HZH) by the approach of network pharmacology and experimental validation in restoring glucose homeostasis, and inflammation in high fat diet fed-streptozotocin (HFD/STZ)-induced type II diabetes (T2DM) rats. Network pharmacology analysis was conducted on 32 bioactive components of HZH. In silico ADME prediction, and physicochemical analysis of 32 compounds were used to assess their drug-likeness. Common targets between selected compounds, and T2DM were subjected for GO enrichment. Compound-target-pathway network was predicted with selected compounds and targets. HZH (300 and 400 mg/kg) were considered for GLUTs expression, and inflammation cytokines in T2DM rats. Network pharmacology showed the core relationship between 13 selected compounds, and 194 key target genes in insulin resistance, type II diabetes mellitus, insulin signaling pathways in T2DM. AKT1, AKT2, GSK3B, IL6, INSR, MAPK8, PPARA, GLUT1, GLUT2, GLUT4 were observed as the key targets in PPI network. HZH-400 significantly restored glucose homeostasis, and inflammatory markers in T2DM rats. It altered GLUT2, GLUT4 expression in liver, and skeletal muscle to normal. Bioactive compounds of HZH were found to control blood sugar level by modulating insulin resistance, type II diabetes mellitus, insulin signaling pathways, and glucose homeostasis, which in turn improved glucose uptake, insulin production in diabetes as shown in network pharmacology and glucose transporter expression studies.

Keywords: GLUTs; HOMA-IR; Hydrolea zeylanica; Inflammatory markers; Network pharmacology; QUICKI.