Nonalcoholic Fatty Liver Disease Therapy: Exploring Molecular Mechanisms of Well-defined Composition from Natural Plants

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, that can progress to nonalcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and eventually lead to liver transplantation. It is linked to obesity and related metabolic syndromes such as type 2 diabetes and hyperlipidemia. NAFLD makes 25% of individuals globally have 5-10% fat accumulating in hepatocytes in the absence of alcohol abuse, hepatitis virus infection, or other secondary causes and debilitating consequences in the quality of life. Up to now, there are no FDA-approved drugs available for NAFLD. Recently, plant-derived substances (such as tea, flaxseed, cinnamon, silybin, soy, curcumin, and licorice root) are playing an increasingly promising role in the treatment and prevention of NAFLD. Studies on the treatment of the NAFLD by these developed natural plants mostly focus on AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and NFκB signaling pathways and antioxidant mechanisms. The pathogenesis of the NAFLD is complicated, which could involve lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, autophagy, epigenetic regulation, immune response disorder, and hepatic microenvironment (such as the hepatoenteric axis changes). Plants are one of the main resources of the drugs, more importantly, the development of a well-defined composition will be more important for drug discovery and NAFLD treatment.

This Research Topic aims to discover and develop novel natural compounds, active ingredients, combination formulas, or prescriptions in plants with therapeutic selectivity that can be used for nonalcoholic fatty liver disease (NAFLD). Meanwhile, the novel discovery of molecular pathogenic mechanisms of NAFLD studies is welcome. This collection of this special issue will contribute cutting-edge evidence on the mechanisms of NAFLD development and make available updated information on novel natural products which have been investigated to treat NAFLD.

In this Research Topic, we welcome pharmacology-focused Original Research, Reviews, Clinical Trials, Methods, and Opinion articles that relate to the following aspects:
• Underlying novel mechanisms or pathways of well-defined composition from natural plants for prevention and treatment of NAFLD (in vitro and in vivo).
• Development of molecular targets, the multi-targets, and synergistic mechanism discovery for compounds from plants.
• Investigation of the efficacy and safety of NAFLD therapy.
• Clinical application of active ingredients in plants in the management of NAFLD.
• The molecular mechanisms of NAFLD occurrence and development.

Note to authors: Only the well-defined composition from plants will be considered in this Research Topic. The plant mixture or extract of uncertain composition will not be accepted.