title: Arctigenin efficiently enhanced sedentary mice treadmill endurance.
abstract: Physical inactivity is considered as one of the potential risk factors for the development of type 2 diabetes and other metabolic diseases, while endurance exercise training could enhance fat oxidation that is associated with insulin sensitivity improvement in obesity. AMP-activated protein kinase (AMPK) as an energy sensor plays pivotal roles in the regulation of energy homeostasis, and its activation could improve glucose uptake, promote mitochondrial biogenesis and increase glycolysis. Recent research has even suggested that AMPK activation contributed to endurance enhancement without exercise. Here we report that the natural product arctigenin from the traditional herb Arctium lappa L. (Compositae) strongly increased AMPK phosphorylation and subsequently up-regulated its downstream pathway in both H9C2 and C2C12 cells. It was discovered that arctigenin phosphorylated AMPK via calmodulin-dependent protein kinase kinase (CaMKK) and serine/threonine kinase 11(LKB1)-dependent pathways. Mice treadmill based in vivo assay further indicated that administration of arctigenin improved efficiently mice endurance as reflected by the increased fatigue time and distance, and potently enhanced mitochondrial biogenesis and fatty acid oxidation (FAO) related genes expression in muscle tissues. Our results thus suggested that arctigenin might be used as a potential lead compound for the discovery of the agents with mimic exercise training effects to treat metabolic diseases.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors: Xuan
authors: X
authors: Tang
authors: Jingjing
authors: J
authors: Zhuang
authors: Jing
authors: J
authors: Chen
authors: Liang
authors: L
authors: Yu
authors: Lihong
authors: L
authors: Hu
authors: Hualiang
authors: H
authors: Jiang
authors: Xu
authors: X
authors: Shen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005080:Exercise Test / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D029001:Herbal Medicine; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010766:Phosphorylation; D057185:Sedentary Behavior; D015398:Signal Transduction
chemical_list: D005227:Fatty Acids; D005663:Furans; D017705:Lignans; D055372:AMP-Activated Protein Kinases; C071942:arctigenin