title: Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFβ/Smads and NF-κB pathways.
abstract: Cardiac remodeling is a key determinant in the clinical course and outcome of heart failure and characterized by cardiac hypertrophy, fibrosis, cardiomyocyte apoptosis and inflammation. The anti-inflammatory, anti-apoptotic and anti-fibrotic effects of paeoniflorin have been identified in various types of tissue and cells. However, the role of paeoniflorin in cardiac remodeling remains unclear. We performed aortic banding (AB) in mice to induce a cardiac remodeling model in response to pressure overload. Paeoniflorin (20 mg/kg) was administered by daily intraperitoneal (i.p.) injection. Paeoniflorin treatment promoted the survival rate and improved cardiac function of mice at 8 weeks post surgery. AB-induced cardiac hypertrophy, as assessed by heart weight, gross heart, HE and WGA staining, cross-sectional area of cardiomyocyte and mRNA expresssion of hypertrophic makers, was attenuated by paeoniflorin. Paeoniflorin also inhibited collagen deposition, expression of TGFβ, CTGF, collagen Iα and collagen IIIα, and phosphorylation of Smad2 and Smad3 in the heart exposed to pressure overload. Cardiomyocyte apoptosis and induction of Bax and cleaved caspase3 in response to AB were suppressed by paeoniflorin. Furthermore, paeoniflorin decreased the quantity of CD68+ cells, protein levels of TNF-α and IL-1β, and phosphorylation of IκBα and NFκB-p65 in the heart after AB. In conclusion, paeoniflorin attenuated cardiac hypertrophy, fibrosis, apoptosis and inflammation, and improved left ventricular function in pressure overloaded mice. The cardioprotective effect of paeoniflorin is associated with the inhibition of TGFβ/Smads and NF-κB pathways.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan 430060, People's Republic of China.
authors: Heng
authors: H
authors: Zhou
authors: He-Xin
authors: HX
authors: Yang
authors: Yuan
authors: Y
authors: Yuan
authors: Wei
authors: W
authors: Deng
authors: Jie-Yu
authors: JY
authors: Zhang
authors: Zhou-Yan
authors: ZY
authors: Bian
authors: Jing
authors: J
authors: Zong
authors: Jia
authors: J
authors: Dai
authors: Qi-Zhu
authors: QZ
authors: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005960:Glucosides / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*; D006027:Glycosides
chemical_list: D001565:Benzoates; D015415:Biomarkers; D001952:Bridged-Ring Compounds; D005960:Glucosides; D039821:Monoterpenes; D016328:NF-kappa B; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C015423:peoniflorin; D006027:Glycosides