Phytotherapy as Multi-Hit Therapy to Confront the Multiple Pathophysiology in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Experimental Interventions

Non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated fatty liver disease (MAFLD), is a metabolic condition distinguished by fat deposition in the hepatocytes. It has a prevalence of about 25% worldwide and is associated with other conditions such as diabetes mellitus, obesity, hypertension, etc. Background and Objectives: There is currently no approved drug therapy for NAFLD. Current measures in the management of NAFLD include lifestyle modification such as an increase in physical activity or weight loss. Development of NAFLD involves a number of parallel hits: including genetic predisposition, insulin resistance, disordered lipid metabolism, mitochondrial dysfunction, lipotoxicity, oxidative stress, etc. Herbal therapy may have a role to play in the treatment of NAFLD, due to their numerous bioactive constituents and the multiple pharmacological actions they exhibit. Therefore, this systematic review aims to investigate the potential multi-targeting effects of plant-derived extracts in experimental models of NAFLD. Materials and Methods: We performed a systematic search on databases and web search engines from the earliest available date to 30 April 2021, using relevant keywords. The study included articles published in English, assessing the effects of plant-derived extracts, fractions, or polyherbal mixtures in the treatment of NAFLD in animal models. These include their effects on at least disordered lipid metabolism, insulin resistance/type 2 diabetes mellitus (T2DM), and histologically confirmed steatosis with one or more of the following: oxidative stress, inflammation, hepatocyte injury, obesity, fibrosis, and cardiometabolic risks factors. Results: Nine articles fulfilled our inclusion criteria and the results demonstrated the ability of phytomedicines to simultaneously exert therapeutic actions on multiple targets related to NAFLD. Conclusions: These findings suggest that herbal extracts have the potential for effective treatment or management of NAFLD.