Tong-xin-luo capsule inhibits left ventricular remodeling in spontaneously hypertensive rats by enhancing PPAR-γ expression and suppressing NF-κB activity

Background Tong-xin-luo capsule (TXL), used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats (SHR). Methods Sixteen eight-week-old SHRs were randomized into an SHR group (n=8) and a TXL group (n=8) that were given Tong-xin-luo capsule (1.5 mg·kg -1 ·d -1 ). Eight Wistar Kyoto (WKY) rats fed with 0.9% NaCI served as the control group (WKY group). Systolic blood pressure (BP), body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 (NF-KB P65) and peroxisome proliferators activated receptor y (PPAR-γ) protein and phosphorylated inhibitor kappa a (IKBα) protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IKBα and NF-KB were measured by co-immunoprecipitation. PPAR-y mRNA, collagen I mRNA and collagen III mRNA were measured by real-time PCR. Results TXL inhibited NF-KB P65 expression and ventricular remodeling and suppressed the activation of NF-KB compared with the SHR group (P<0.01, P<0.05). TXL reduced IKBα phosphorylation, increased expression of PPAR-y protein and enhanced the physical interaction of the P65-P50 heterodimer with IKBα. The mRNA expression of PPAR-y was enhanced but the mRNA expression of collagen I mRNA and collagen III mRNA were suppressed by TXL. Conclusions In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process of TXL increasing the expression of PPAR-y that could result in the inhibition of the activation of NF-KB.