6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-01, Vol.29 (2), p.419
• Main Authors: Yang, Ah Young, Kim, Kiryeong, Kwon, Hyun Hee, Leem, Jaechan, Song, Jeong Eun
• Format: Article
• Language: English
• Subjects: 6-shogaol; Amino acids; Analysis; Animals; Antioxidants; Apoptosis; Biochemistry; Biomarkers; Body weight; Catechols; Cell Death; Choline; Diet; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Enzymes; Fibrosis; Health aspects; Hepatitis; Inflammation; Inflammation - drug therapy; Kinases; Lipids; Liver; Liver Cirrhosis - drug therapy; Liver Cirrhosis - etiology; Liver diseases; Male; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; non-alcoholic steatohepatitis; Oxidative Stress; Pathogenesis; Proteins; Racemethionine; Tumor necrosis factor-TNF
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29020419

Non-alcoholic steatohepatitis (NASH) is becoming an increasingly serious global health threat, distinguished by hepatic lipid accumulation, inflammation, and fibrosis. There is a lack of approved pharmaceutical interventions for this disease, highlighting the urgent need for effective treatment. This study explores the hepatoprotective potential of 6-shogaol, a natural compound derived from ginger, in a methionine- and choline-deficient (MCD) dietary mouse model of NASH. Male C57BL/6J mice were subjected to the MCD diet for 4 weeks to induce NASH, with concurrent intraperitoneal administration of 6-shogaol (20 mg/kg) three times a week. While 6-shogaol did not impact body weight, liver weight, or hepatic lipid accumulation, it effectively mitigated liver injury, inflammation, and fibrosis in MCD diet-fed mice. Mechanistically, 6-shogaol inhibited lipid and DNA oxidation, restored hepatic glutathione levels, and regulated the expression of pro-oxidant and antioxidant enzymes. Furthermore, 6-shogaol inhibited apoptosis and necroptosis, as indicated by a decrease in TUNEL-stained cells and downregulation of apoptosis- and necroptosis-associated proteins. Additionally, 6-shogaol alleviated endoplasmic reticulum (ER) stress, as demonstrated by decreased expression of molecules associated with unfolded protein response pathways. These findings underscore the potential of 6-shogaol as a therapeutic intervention for NASH by targeting pathways related to oxidative stress, cell death, and ER stress.