Protective Effects of Gnetin C from Melinjo Seed Extract against High-Fat Diet-Induced Hepatic Steatosis and Liver Fibrosis in NAFLD Mice Model

• Published in: Nutrients Vol. 15; no. 18; p. 3888
• Main Authors: Kabir, Tohfa, Yoshiba, Haruki, Agista, Afifah Zahra, Sultana, Halima, Ohsaki, Yusuke, Yeh, Chiu-Li, Hirakawa, Ryota, Tani, Hiroko, Ikuta, Tomoki, Nochi, Tomonori, Yang, Suh-Ching, Shirakawa, Hitoshi
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2023; MDPI
• Subjects: Blood sugar; Diabetes; Diet; Fatty acids; Fibrosis; Glucose; gnetin C; hepatic fibrosis; hepatic steatosis; Instrument industry; Insulin; Kinases; Lipids; Liver cancer; Liver cirrhosis; Liver diseases; Metabolism; NAFLD; Plasma; Resveratrol; RNA; Seeds; Transforming growth factors; United States; Japan
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15183888

Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, can progress to hepatic steatosis, inflammation, and advanced fibrosis, increasing the risk of cirrhosis. Resveratrol, a natural polyphenol with antioxidant and anti-inflammatory properties, is beneficial in treating multiple metabolic diseases. Gnetin C, a resveratrol derivative obtained from Melinjo seed extract (MSE), shares similar health-promoting properties. We investigated the role of gnetin C in preventing NAFLD in a mouse model and compared it with resveratrol. Male C57BL/6J mice were fed a control diet (10% calories from fat), a high-fat choline-deficient (HFCD) diet (46% calories from fat) and HFCD diet supplemented with gnetin C (150 mg/kg BW·day−1) or resveratrol (150 mg/kg BW·day−1) for 12 weeks. Gnetin C supplementation reduced body and liver weight, and improved blood glucose levels and insulin sensitivity. Both gnetin C- and resveratrol reduced hepatic steatosis, with gnetin C also decreasing liver lipid content. Gnetin C and resveratrol ameliorated HFCD diet-induced hepatic fibrosis. The mRNA expression results, and western blot analyses showed that gnetin C and, to some extent, resveratrol downregulated fibrosis markers in the TGF-β1 signaling pathway, indicating a possible safeguarding mechanism against NAFLD. These results suggest that gnetin C supplementation may protect against lipid deposition and hepatic fibrosis.