Histone deacetylase (HDAC) inhibitor curcumin upregulates mitochondrial uncoupling protein1 (UCP1) and mitochondrial function in brown adipocytes, in-silico study and screening natural drug library

Abstract

Mitochondrial dysfunction has been associated with diverse pathological conditions globally. Specifically, in adipose tissues, mitochondrial dysfunction is the primary cause of obesity and obesity-related illnesses. An existing drugs such as atorvastatin and other lipid-lowering drugs demonstrated adverse effects and initiated other diseases. Thus, we need to explore new methods to prevent and treat obesity. In this study, we used the cell screening method to identify several natural compounds that increase adipocyte UCP1 gene expression. The identified drug Curcumin was evaluated in cell models and the In-silico model. We found curcumin is an active compound of turmeric belonging to Zingiberaceae (ginger family), which activates the Nrf2 mechanism. Curcumin potentially endorses the expression of UCP1 in the brown adipocyte in vitro cellular model. Curcumin plays an important role that modulating mitochondrial function and improving mitochondrial DNA quantification, ATP production, and cell viability. We have established an efficient in vitro cell experiment system to study the metabolic regulation of UCP1. The in-silico model revealed curcumin-UCP1 interaction. Curcumin, via enhancing mitochondrial activity, could be a helpful therapeutic molecule against metabolic disorders or obesity-related diseases. Curcumin will be the subject of more research in both human and murine models, which will provide novel therapeutic pathways for the treatment of metabolic illnesses by modulating the control of mitochondrial function.