title: Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF-κB and MAPKs activation via the phosphatidylinositol 3-kinase signaling.
abstract: The phenolic glucoside gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties. However, the role and precise molecular mechanisms explaining how gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown. To study this, rat H9c2 cardiomyocytes were treated with gastrodin and/or lipopolysaccharide (LPS). Our results showed that gastrodin treatment strongly suppressed nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) family activation and upregulation of the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-stimulated H9c2 cardiomyocytes. Simultaneously, gastrodin obviously upregulated the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling in a dose-dependent manner. However, wortmannin, a specific PI3-K inhibitor, blocked the inhibitory effects of gastrodin on LPS-stimulated H9c2 cardiomyocytes. Furthermore, PI3-K/Akt inhibition partially abolished the inhibitory effects of gastrodin on the phosphorylation of inhibitor κB-α (IκB-α), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and activity of NF-κB. Here we report activation of the PI3-K/Akt signaling by gastrodin and that inhibition of this pathway reverses the inhibitory effects of gastrodin on NF-κB and MAPKs activation in H9c2 cardiomyocytes.
authors: Department of Anatomy, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China. yangping19871022@gmail.com
authors: Ping
authors: P
authors: Yang
authors: Yi
authors: Y
authors: Han
authors: Li
authors: L
authors: Gui
authors: Jun
authors: J
authors: Sun
authors: Yuan-li
authors: YL
authors: Chen
authors: Rui
authors: R
authors: Song
authors: Jia-zhi
authors: JZ
authors: Guo
authors: Ya-nan
authors: YN
authors: Xie
authors: Di
authors: D
authors: Lu
authors: Lin
authors: L
authors: Sun
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D005960:Glucosides / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D001592:Benzyl Alcohols; D005960:Glucosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C045345:gastrodin; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D000077191:Wortmannin