title: Madecassoside suppresses LPS-induced TNF-alpha production in cardiomyocytes through inhibition of ERK, p38, and NF-kappaB activity.
abstract: Madecassoside (MA) is a major triterpenoid component of Centella asiatica that has a wide range of biological activities, including wound-healing and antioxidative activities. In the present study, we evaluated the therapeutic effect of MA on rat cardiac dysfunction during sepsis induced by lipopolysaccharide (LPS), as well as the possible mechanism. Pretreatment of the neonatal rat cardiomyocytes with MA inhibited LPS-induced TNF-alpha production in a concentration-dependent manner. In addition, pretreatment of the rats with MA (20 mg/kg, i.g.) significantly inhibited the elevation of plasma TNF-alpha, delayed the fall of mean arterial blood pressure, and attenuated the tachycardia induced by LPS. We further observed that MA prevented the LPS-induced nuclear factor-kappa B (NF-kappaB) translocation from the cytoplasm into the nucleus, and inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38. These results suggest that MA inhibits LPS-stimulated TNF-alpha production through the blocking of ERK1/2, p38 and NF-kappaB pathways in cardiomyocytes. MA may have cardioprotective effects in LPS-mediated sepsis.
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Li
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hou
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Zeng
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Xie
authors.forename: Si-Wang
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D028041:Centella; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015533:Transcriptional Activation / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C093443:madecassoside; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases