Advancements in Plant-Based Therapeutics for Hepatic Fibrosis: Molecular Mechanisms and Nanoparticulate Drug Delivery Systems

Abstract

Chronic liver injuries often lead to hepatic fibrosis, a condition characterized by excessive extracellular matrix accumulation and abnormal connective tissue hyperplasia. Without effective treatment, hepatic fibrosis can progress to cirrhosis or hepatocellular carcinoma. Current treatments, including liver transplantation, are limited by donor shortages and high costs. As such, there is an urgent need for effective therapeutic strategies. This review focuses on the potential of plant-based therapeutics, particularly polyphenols, phenolic acids, and flavonoids, in treating hepatic fibrosis. These compounds have demonstrated anti-fibrotic activities through various signaling pathways, including TGF-β/Smad, AMPK/mTOR, Wnt/β-catenin, NF-κB, PI3K/AKT/mTOR, and hedgehog pathways. Additionally, this review highlights the advancements in nanoparticulate drug delivery systems that enhance the pharmacokinetics, bioavailability, and therapeutic efficacy of these bioactive compounds. Methodologically, this review synthesizes findings from recent studies, providing a comprehensive analysis of the mechanisms and benefits of these plant-based treatments. The integration of novel drug delivery systems with plant-based therapeutics holds significant promise for developing effective treatments for hepatic fibrosis.

Keywords: flavonoids; hepatic fibrosis; phenolic acids.

Figure 1

A diagram of signaling pathways modulated by polyphenols and their drug delivery systems in hepatic fibrosis. This figure was created with BioRender.com.

Figure 2

A diagram illustrating the role of immune cells and immune responses mediated by polyphenols in the resolution of liver fibrosis. This figure was created with BioRender.com.