Methodologies for Investigating Natural Medicines for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD)

Moon      Sun Kim; Sidney      Kung; Thomas      Grewal; Basil      D. Roufogalis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is emerging as a prominent condition in Western countries. In this review we describe the characteristics and current treatments of NAFLD and discuss opportunities for developing new therapeutic management approaches, with a particular emphasis on development of animal studies and in vitro assays for identification of components of natural product medicines. The main manifestation of NAFLD is hepatic lipid accumulation in the form of lipid droplets (LDs), known as hepatic steatosis (fatty liver). Current treatments for NAFLD generally aim to reduce triglyceride (TG) accumulation, often utilizing thiazolidinedines (TZDs) and fibrates, which are known to lower TG levels in hyperlipidemia, diabetes and metabolic syndrome. Both of these compounds act through activation of nuclear receptors of the Peroxisome Proliferator-Activated Receptor (PPAR) family, thereby activating genes involved in triglyceride metabolism. Thus treatment using natural PPAR and PPAR ligands, such as polyunsaturated fatty acids (PUFA), has also been considered. Alternatively, natural medicines for the treatment of NAFLD have a long and successful history of controlling disease without prominent side effects. However, active compounds in natural medicine responsible for lowering hepatic TG levels are yet poorly characterized. This points to the need for medium-high throughput screening assays to identify active components within natural herbs. As outlined in this review, the quantification of the size and number of lipid droplets could provide an opportunity to screen compound libraries derived from natural medicine for their potential to reduce NAFLD.

Keywords: Nonalcoholic fatty liver disease (NAFLD), fibrates, thiazolidinediones (TZD), natural medicines, automated screening assays, natural herbs, hepatic steatosis, hepatic TG accumulation, metabolic perturbations, metabolic syndrome, plasma glucose, hepatic necroinflammation, non-alcoholic hepatic steatosis, hormonal and non-hormonal regulators