In vitro, ex vivo and in vivo anti-hypertensive activity of Chrysophyllum cainito L. extract.

Chrysophyllum cainito L., a traditional herbal medicine, could have the potential for management of hypertension due to presence of polyphenolic compounds. The extracts and fractions of the pulp of plant were evaluated for in vitro (inhibition of angiotensin I converting enzyme/ACE assay), ex vivo (isolated aorta relaxation assay) and in vivo (salt induced hypertensive rat assay). The alcoholic and aqueous extract (ALE and AQE respectively) of fruit of plant C. cainito was having 14.8 and 9.2% yield respectively. The fractionation with ethyl alcohol (EAF) and butanol (BTF) yielded 2.52 & 2.17% respectively from ALE and 0.46 & 0.31% respectively from AQE with respect to fruit pulp dry weight. More phenolic content was found in ALE (3.75±0.15 mg gallic acid equivalent or GAE g(-1) of dry power of fruit pulp) compared to AQE and maximum in ethyl acetate fraction of ALE (ALE-EAF) (2.32±0.21 mg GAE g(-1) of dry power of fruit pulp) among all fractions. ACE inhibition activity was found to be maximum in ALE-EAF 62.5±7.34%. While ex vivo study using isolated tissue of aorta showed again showed maximum activity (62.82±6.19 and 46.47±8.32% relaxation with 50 µg mL(-1) and 10 µg mL(-1) GAE concentration respectively). ALE-EAF reduced the elevated arterial pressure of salt induced hypertensive rat significantly to the level of normotensive animal group. Results of ALE-EAF have shown its potential as a source for novel constituent for the treatment hypertension and should further be studied for isolation of specific constituent for more effectiveness.

Huang-lian-jie-du-tang protects rats from cardiac damages induced by metabolic disorder by improving inflammation-mediated insulin resistance.

Huang-lian-jie-du-tang (HLJDT), a traditional Chinese medicine, has been shown to improve insulin resistance (IR) induced by inflammation, a key event in the development of metabolic syndrome (MS). The present study aimed to investigate the protective effects of HLJDT on MS and explore the underlying mechanism. MS rats were established with obese-diets and treated with normal saline, aspirin or HLJDT. The myocardial lesions were identified by echocardiogram, transmission electron microscope, and Sirius-red staining. The inflammatory cytokines were measured by ELISA and real-time PCR. The activation of NF-κB, JNK, SOCS3, IRS1 and AKT in the heart was detected by immunohistochemistry and Western blot analysis. Compared with the controls, MS rats developed obvious obesity, hypertension, dyslipidemia, IR, inflammation, and cardiac damage. Moreover, phosphorylated IRS-1 at Ser307 was correlated with the activation of NF-κB, JNK and SOCS3 and the inhibition of AKT in the heart from MS rats. These data suggest that serine phosphorylation of IRS-1 in response to inflammation is mediated, in part, by NF-κB, JNK and SOCS3. Notably, HLJDT inhibited the activation of NF-κB and reduced serine phosphorylation of IRS-1. In summary, HLJDT protects myocardium from IR-mediated injury by inhibiting serine phosphorylation of IRS-1 in MS rats.

Tong-xin-luo capsule inhibits left ventricular remodeling in spontaneously hypertensive rats by enhancing PPAR-gamma expression and suppressing NF-kappaB 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 x kg(-1) x d(-1)). Eight Wistar Kyoto (WKY) rats fed with 0.9% NaCl 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-kappaB P65) and peroxisome proliferators activated receptor gamma (PPAR-gamma) protein and phosphorylated inhibitor kappa alpha (IkappaBalpha) protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IkappaBalpha and NF-kappaB were measured by co-immunoprecipitation. PPAR-gamma mRNA, collagen I mRNA and collagen III mRNA were measured by real-time PCR. RESULTS: TXL inhibited NF-kappaB P65 expression and ventricular remodeling and suppressed the activation of NF-kappaB compared with the SHR group (P < 0.01, P < 0.05). TXL reduced IkappaBalpha phosphorylation, increased expression of PPAR-gamma protein and enhanced the physical interaction of the P65-P50 heterodimer with IkappaBalpha. The mRNA expression of PPAR-gamma was enhanced but the mRNA expression of collagen I mRNA and collagen I 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-gamma that could result in the inhibition of the activation of NF-kappaB.