Pathophysiology

Background: Liver fibrosis is a progressive global disease characterized by persistent inflammation and excessive extracellular matrix (ECM) deposition, which can lead to cirrhosis and liver cancer. Currently, limited treatments are available for liver fibrosis, making the development of safe and effective therapeutic drugs crucial. Purpose: This study aimed to evaluate the anti-fibrotic effects of Meconopsis bhutanica extract (MBE) on liver fibrosis, analyze its pharmacological components, and explore its underlying mechanisms using multi-omics approaches. Methods: Phytochemical analysis was performed by LC-MS profiling as well as NMR experiments. C57BL/6 mice were then intraperitoneally injected twice a week with 10% CCl4 for 6 weeks. The prevention group was continuously gavaged with MBE daily. Transcriptomic and metabolomic analyses were employed to identify the mechanisms involved in its anti-fibrotic effects. Results: The study of the phytochemical composition showed that flavonoids and phenylethanoid glycosides are the main active components in MBE. Treatment with MBE (100 mg/kg or 400 mg/kg) significantly reduced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), while enhancing the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). MBE also decreased malondialdehyde (MDA) and inflammatory-related cytokines. Furthermore, MBE suppressed hepatic fibrosis markers and reduced lipid accumulation. MBE activated peroxisome proliferator-activated receptor γ (PPARγ), inhibited mitogen-activated protein kinases (MAPKs), and modulated taurine and hypotaurine metabolism. Conclusion: MBE exerted anti-inflammatory and antioxidant effects by activating PPARγ, inhibiting MAPKs, regulating taurine and hypotaurine metabolism, and reducing lipid levels, thereby inhibiting liver fibrosis. These findings highlighted the potential of MBE as a promising therapeutic agent for liver fibrosis.

Jun 1, 2025