Fanlian Huazhuo Formula: A promising herbal preparation for metabolic liver disease

Abstract

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased significantly in recent decades and is projected to increase further due to the rising obesity rates. MASLD patients are at higher risk of developing advanced liver diseases “cirrhosis and hepatocellular carcinoma” as well as liver- or cardiovascular-related mortality. Existing lipid-lowering therapies failed to reduce the risk of mortality in these patients. Therefore, there is an urgent need for pharmacotherapies that can control and even reverse this disease. Fanlian Huazhuo Formula (FLHZF) is a combination herbal preparation, and its various individual constituents regulate hepatic lipid metabolism, adipose tissue inflammation, and gut microbiota. Despite, these useful effects, limited information is available on its benefits in diet-induced hepatosteatosis. In this article, we discuss the research findings recently published about the therapeutic effects of FLHZF in suppressing MASLD development and underlying mechanisms. Utilizing a series of in vitro and in vivo experiments, the authors demonstrated for the first time that FLHZF suppresses MASLD in male mice possibly by inhibiting hepatic de novo lipogenesis pathways and reducing hepatocyte death. This study paves the way for future investigations aimed at investigating FLHZF’s role in inhibiting lipogenesis particularly using radioactively-labeled glucose and acetate, and governing hepatocyte mitochondrial function, gut microbiome profile, and its effects in other models of MASLD, and female mice.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Fanlian Huazhuo Formula; De novo lipogenesis; Cell death; Adenosine-5’-monophosphate-activated protein kinase alpha; Acetyl-CoA carboxylase

Core Tip: Various constituents of Fanlian Huazhuo Formula (FLHZF) have been shown to regulate several metabolic and inflammatory parameters in diabetic mice, including hepatic lipid metabolism and injury, body weight, adipose tissue inflammation, and gut microbiota. Niu et al reported novel insights into the therapeutic benefits of FLHZF in diet-induced metabolic dysfunction-associated steatotic liver disease using various complementary approaches. However, future studies are required to better understand the underlying molecular mechanisms, determine the therapeutic efficacy of FLHZF in other models, and rule out its sex-specific benefits.