Sangyod rice extract mitigates insulin resistance in HepG2 cells and hepatic steatosis in diabetic rats via AMPK/mTOR/MAPK signaling pathways

• Published in: Food bioscience Vol. 61; p. 104662
• Main Authors: Hanchang, Wanthanee, Woonnoi, Wanwipha, Saetan, Jirawat, Suttithumsatid, Wiwit, Tanasawet, Supita, Sanprick, Amornrat, Moolsup, Furoida, Sukketsiri, Wanida
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2024
• Subjects: HepG2 cells; Insulin resistance; Non-alcoholic fatty liver disease; Nuclear factor kappa B; Oryza sativa; Type 2 diabetes; Type 2 diabetes; Oryza sativa; Insulin resistance; HepG2 cells; Non-alcoholic fatty liver disease; Nuclear factor kappa B
• ISSN: 2212-4292; 2212-4306
• DOI: 10.1016/j.fbio.2024.104662

Non-alcoholic fatty liver disease (NAFLD), marked by inflammation, oxidative stress, and insulin resistance (IR), often has a significant impact on public health. To date, Sangyod rice (SR) has been found to inhibit adipocyte adipogenesis; however, its impact on NAFLD in an animal model remains unexplored. The present study investigated the effects of SR ethanolic extract (SREE) on NAFLD in an experimental model induced by a high-fat diet (HFD) and streptozotocin (STZ). Additionally, the effect of SREE on IR was also evaluated in HepG2 cells. In IR HepG2 cells, SREE and the positive drug metformin caused an increase in glucose uptake. Furthermore, SREE and metformin downregulated the expression of the following gens: acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FasN), microsomal triglyceride transfer protein (MTTP), sterol regulatory element-binding proteins (SREBP)-2, and SREBP-1c. In contrast, SREE and metformin upregulated the expression of carnitine palmitoyltransferase-1 (CPT-1α) gene in the IR HepG2 cells. In animal model, the study included five groups: normal control, diabetes (DM) with HFD only, DM with HFD plus metformin, and DM with HFD supplemented with either 250 or 500 mg/kg body weight of SREE. SREE at the highest dose declined hepatic lipid contents, de novo lipogenesis enzymes, inflammatory cytokines, and oxidative stress similar to the positive drug metformin. Moreover, SREE exerts potent and multifaceted pharmacological actions, including the reduction of oxidative stress, inhibition of inflammatory reactions by blocking the nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways, and mitigation of IR by restoring the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) axis. As a result, SREE attenuated hepatic steatosis, liver inflammation, and oxidative stress in HFD and STZ-induced NAFLD in rats, suggesting its potential for NAFLD prevention.