Anti-hepatic fibrosis activity and mechanisms of natural polysaccharides: A comprehensive review

Hepatic fibrosis (HF) can be reversed via a self-repair mechanism targeting the activation of hepatic stellate cells (HSCs), which are considered the central driving force behind its progression. Currently, many inhibitors or antagonists of HF are in the development phase. However, research is often halted due to adverse reactions triggered by drug interactions or because the drugs fail to demonstrate significant efficacy, with many trials being discontinued at phase II. Natural polysaccharides have shown notable advantages in treating HF, making them promising candidates for therapy. This review summarizes the mechanisms involved in the activation of HSCs, including the roles of inflammatory immune response, oxidative stress, gut microbiota, epithelial-mesenchymal transition, ferroptosis, exosomes, and signaling pathways, with particular emphasis on the role of inflammation. Furthermore, it reviews the latest research on natural polysaccharides targeting these mechanisms in the treatment of HF, such as plant-derived, fungal, and marine polysaccharides. Additionally, the clinical applications of polysaccharides, their multifunctionality as drug carriers, and the challenges associated with these applications have been discussed, along with potential strategies to address these challenges. This article aims to provide new insights into the development of clinical drugs targeting HSCs for the treatment of HF.