Abstract
Background: Liver fibrosis driven by chronic injury oxidative stress and inflammation represents a significant global health burden Natural compounds such as protocatechuic acid PCA and DCarvone DCar possess known antioxidant and antiinflammatory properties but their combined therapeutic potential against liver fibrosis remains unexplored
Purpose: This study aimed to investigate the synergistic antifibrotic effects of PCA and DCar in both cellular and animal models of liver fibrosis
Study design: A combined in vitro and in vivo approach was employed In vitro experiments utilized the HSCT6 hepatic stellate cell line while in vivo studies involved a CClinduced liver fibrosis rat model
Methods: HSCT6 cells were treated with PCA 50 M and DCar 50 ngmL individually and in combination Cytotoxicity MTT assay apoptosis flow cytometry and Hoechst staining and Annexin A2 levels were assessed In rats with CClinduced fibrosis body weight liver enzymes ALT AST ALP albumin LDH activity fibrotic markers TIMP1 Col11 antioxidant enzymes SOD Cyp2e1 inflammatory cytokines IL6 TNF NFB and histological changes were evaluated following treatment with PCA DCar or their combination
Results: PCADCar treatment significantly improved HSCT6 cell morphology reduced cytotoxicity p 0001 and decreased apoptosis compared to individual treatments In vivo PCADCar restored body weight normalized liver enzymes downregulated TIMP1 and Col11 enhanced antioxidant activity and reduced inflammatory markers p 001 Histological analysis confirmed improved liver architecture with reduced fibrosis and inflammation
Conclusion: The combination of PCA and DCar exhibits synergistic antifibrotic effects by mitigating oxidative stress inflammation and extracellular matrix deposition These findings highlight its potential as a dietary or therapeutic strategy for liver fibrosis warranting further clinical exploration
Keywords: Liver Fibrosis Oxidative Stress Inflammation Protocatechuic Acid DCarvone Synergistic Effect