journal article Dec 04, 2015

Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in Nonalcoholic Fatty Liver Disease through the AMPK/Nrf2 Pathway

Phytotherapy Research Vol. 30 No. 3 pp. 402-411 · Wiley
Abstract
This study was designed to investigate the antioxidative, antiinflammatory and metabolism‐regulating effects of gastrodin (GSTD) in the treatment of nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) was used to induce steatosis in HL‐7702 cells; a high‐fat or high‐fat and high‐cholesterol diet was used to induce NAFLD in mice and rats. Our results showed that GSTD significantly increased hepatic superoxide dismutase (SOD) but decreased reactive oxygen species (ROS)/malondialdehyde (MDA) and reduced the mRNA levels of proinflammatory cytokines both in vitro and in vivo. GSTD promoted the phosphorylation of nuclear factor erythroid‐2‐related factor‐2 (Nrf2) at serine (Ser) 40, stimulated its nuclear translocation and increased hepatic expression of heme oxygenase‐1 (HO‐1). GSTD activated AMP‐activated protein kinase (AMPK), suppressed hepatic steatosis, lowered serum triglyceride (TG)/glucose and decreased body weight gain in animals with NAFLD. The stimulating effects of GSTD on the Nrf2 pathway as well as its antioxidative/antiinflammatory activities were abolished by compound C in OA‐treated HL‐7702 cells. In summary, our results demonstrate that GSTD activates the AMPK/Nrf2 pathway, ameliorates oxidative stress/proinflammatory response and improves lipid metabolism in NAFLD. Our findings may support the future clinical application of GSTD for the treatment of NAFLD to reduce hepatic steatosis, oxidative stress and proinflammatory response. Copyright © 2015 John Wiley & Sons, Ltd.
Topics

No keywords indexed for this article. Browse by subject →

References
40
[3]
Structural and functional characterization of Nrf2 degradation by glycogen synthase kinase 3/β-TrCP

Antonio Cuadrado

Free Radical Biology and Medicine 10.1016/j.freeradbiomed.2015.04.029
[6]
Geng Y "Experimental study of Gastrodia Powder in improving hepatic steatosis in rats intragastrically administered with fat emulsion" Chin Med Her (2013)
[7]
Geng Y "Gastrodin ameliorates oleic acid‐induced fat accumulation through activation of AMPK pathway in HL‐7702 cells" Chin Pharmacol Bull (2015)
[8]
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

Jorge Henao-Mejia, Eran Elinav, Chengcheng Jin et al.

Nature 10.1038/nature10809
[14]
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway

Thomas W. Kensler, Nobunao Wakabayashi, Shyam Biswal

Annual Review of Pharmacology and Toxicology 10.1146/annurev.pharmtox.46.120604.141046