A triterpenoid-enriched extract of bitter melon leaves alleviates hepatic fibrosis by inhibiting inflammatory responses in carbon tetrachloride-treated mice

• Published in: Food & function Vol. 12; no. 17; pp. 785 - 7815
• Main Authors: Chang, Mei-Ling, Lin, Yu-Ting, Kung, Hsiu-Ni, Hou, Yu-Chen, Liu, Jun-Jen, Pan, Min-Hsiung, Chen, Hui-Ling, Yu, Chun-Hsien, Tsai, Po-Jung
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 07.09.2021
• Subjects: Actin; Alanine; Alanine transaminase; Alanine Transaminase - genetics; Alanine Transaminase - immunology; Animal tissues; Animals; Anti-Inflammatory Agents - administration & dosage; Aspartate aminotransferase; Aspartate Aminotransferases - genetics; Aspartate Aminotransferases - immunology; Carbon; Carbon tetrachloride; Carbon Tetrachloride - adverse effects; Collagen; Cytokines; Deposition; Dietary supplements; Fibrosis; Gene expression; Growth factors; Humans; Inflammation; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - immunology; Liver; Liver - drug effects; Liver - enzymology; Liver - immunology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - genetics; Liver Cirrhosis - immunology; Liver diseases; Male; Metastases; Mice; Mice, Inbred ICR; Momordica charantia - chemistry; Monocytes; Muscles; Plant Extracts - administration & dosage; Plant Leaves - chemistry; Smooth muscle; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-like receptors; Transforming growth factor-b; Triterpenes - administration & dosage; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d1fo00884f

Liver fibrosis is a progression of chronic liver disease characterized by excess deposition of fibrillary collagen. The aim of this study was to investigate the protective effect of a triterpenoid-enriched extract (TEE) from bitter melon leaves against carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in mice. Male ICR mice received TEE (100 or 150 mg kg −1 ) by daily oral gavage for one week before starting CCl 4 administration and throughout the entire experimental period. After intraperitoneal injection of CCl 4 for nine weeks, serum and liver tissues of the mice were collected for biochemical, histopathological and molecular analyses. Our results showed that TEE supplementation reduced CCl 4 -induced serum aspartate aminotransferase and alanine aminotransferase activities. Histopathological examinations revealed that CCl 4 administration results in hepatic fibrosis, while TEE supplementation significantly suppressed hepatic necroinflammation and collagen deposition. In addition, TEE supplementation decreased α-smooth muscle actin (α-SMA)-positive staining and protein levels of α-SMA and transforming growth factor-β1. TEE-supplemented mice had lower mRNA expression levels of interleukin-6, tumor necrosis factor-α, and toll-like receptor 4. Moreover, TEE (150 mg kg −1 ) supplementation significantly reduced intrahepatic inflammatory Ly6C + monocyte infiltration. We demonstrated that TEE could ameliorate hepatic fibrosis by regulating inflammatory cytokine secretion and α-SMA expression in the liver to reduce collagen accumulation. A triterpenoid-enriched extract isolated from bitter melon leaves exhibited a hepatoprotective effect in CCl 4 -induced experimental fibrosis.