Targeting NAFLD and NASH with Tinospora crispa: insights from network pharmacology and molecular dynamics

Abstract

Introduction

Tinospora crispa (TC), also known as ‘Petawali,’ is an Indian medicinal plant renowned in folk medicine and Ayurveda for its extensive therapeutic properties. Despite its known benefits, the hepatoprotective potential of TC, particularly against Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH), remains unexplored scientifically. This study aims to identify phytocompounds in TC that may be effective against NAFLD/NASH-related targets and elucidate their mechanisms of action.

Method

We utilised fingerprint-based similarity search analyses to predict targets for each phytocompound. Network pharmacology, facilitated by ‘Cytoscape’ and its ‘Cytohubba’ plugins, was employed to establish connections between specific phytocompounds of TC and potential targets of NAFLD. Molecular docking followed by MM/GB(PB)SA scoring analyses were performed with these phytochemicals against a range of crystal structures and homology models of biological target proteins. Around 500 ns molecular dynamics simulations were conducted for the selected biological targets and docked phytoconstituents to understand dynamic behaviours of the complexes.

Result

Molecular docking and MM/GB(PB)SA scoring revealed that 3′-O-methylluteolin, diosmetin, genkwanin, and luteolin may show promising activity whereas molecular dynamics simulation highlighted that 3′-O-methylluteolin might be the most suitable phytochemical for NAFLD treatment.

Conclusion

Overall, these four compounds may modulate key proteins such as CYP3A4, MMP1, PPARδ, PPARγ, AKT1, CYP1A2, and STAT3. This study provides a scientific basis for the potential use of TC in managing NAFLD and NASH, encouraging further research and development in this domain.