Fazlin M. Fauzi
Universiti Teknologi MARA, Malaysia
Title: Understanding the mode-of-action of Cassia auriculata via in silico and in vivo studies and its evaluation as a long term therapy for type II diabetes
Biography
Biography: Fazlin M. Fauzi
Abstract
One of the long term complications of current oral anti-diabetic drugs is their damage to the immune system. Given the medical need in this area, in the current work we investigated the Ayurvedic anti-diabetic treatment Cassia auriculata (CA) in order to understand its mode-of-action (MOA) via combined cheminformatics and in vivo biological readouts, and to assess its potential therapeutic effect in the immunometabolic system. To this end, the synergism between 10 polyphenolic constituents of CA in modulating insulin and immunoprotective pathways were studied. In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signaling, based on a model trained on known bioactivity data and chemical similarity considerations. CA was furthermore subjected to in vivo studies where induced T2DM rats were treated with CA for 28 days and expression of genes relating to gluconeogenesis (PKC-1,G6PC), glucose transport (GLUT-2, GLUT-4), insulin sensitivity (INS-1, PEPCK), cytokine genes (IL-6,IFN-γ,TNF-α,NF-κb,PPAR-γ) and inflammatory markers (CRP) were measured. In the in silico study, with the exception of Catechin, all other polyphenols are predicted to modulate key targets of insulin signaling such as PI3K and PPAR with a high probability value. These results were corroborated by in vivo studies, where CA-treated rats shows reduced serum glucose and HbA1c, increased plasma level of C-peptide and insulin compared to control. Additionally, increased glucose transport, reduced gluconeogenesis and oxidative phosphorylation were observed, thus improving peripheral utilization of glucose and insulin sensitivity in the tissues. Furthermore, reduction in inflammatory cytokines by CA improves insulin signaling and reduces cellular damage. Hence, the therapeutic and protective effect of CA in T2DM can be better understood with the current study by a combination of in silico and in vivo analyses.