| Objective:Fargesin is a neolignan isolated from Magnolia plants such as Magnolia biondiiand and Magnoliae flos, which are widely used in the treatment of managing rhinitis,inflammatory, histamine, sinusitis and headache. In our previous studies, we had successfully made a model of vascular smooth muscle/cell membrane chromatography(VSM/CMC). This model was established to varify the interaction between active compounds and target receptors in the vascular smooth muscle cell membrane. We found that fargesin had chromatographic retention in the VSM/CMC models and had vasorelaxant effect in rat aortic ring assays, indicating that it may have the antihypertensive effects, so we need further study on the pharmacological activity and mechanisms of fargesin.Methods:We developed a 2-kidney, 1-clip(2K1C) model of hypertension to investigate its possible antihypertensive effects. After 6 weeks, the systolic blood pressure(SBP) was measured using the tail-cuff method in conscious rats. Only hypertensive rats(SBP≥150mm Hg) were used in the experiments. The 2K1 C hypertensive rats were divided into six groups(n=8/group), named: SHAM(sham surgery-treated with vehicle), MODEL(2K1C surgery-treated with vehicle), CAP(2K1C surgery-treated with captopril, 25 mg/kg/day),Far-H(2K1C surgery-treated with fargesin, 50 mg/kg/day), Far-M(2K1C surgery-treated with fargesin, 25 mg/kg/day) and Far-L(2K1C surgery-treated with fargesin, 12.5mg/kg/day). In the model and control groups, rats received the indicated preparations or identical quantities of vehicle(0.5% sodium carboxymethyl cellulose as placebo) orally by daily gavage for 5 weeks, respectively. After the last measurement of blood pressure and weight, animals were anaesthetised and blood was taken from the rats’ abdominal aorta.Anesthetized rats were sacrificed and then their livers and hearts were carefully excised,cleaned, and then weighed. All biological samples were stored until analysis. And wedetected malondialdehyde, angiotensin II, endothelin-1 levels and activities of superoxide dismutase, catalase, nitric oxide synthase, glutathione peroxidase by commercial kits and analyze using a spectrophotometer.Results:Blood pressure kept stable throughout the 6 weeks experimental study period in the sham group. After the left renal artery was clipped, blood pressure increased gradually in the 2K1 C model group. Treating with fargesin to the hypertensive rats produced an obvious decline of the blood pressure. During the experimental period, the heart weight,left ventricular and the heart weight/body weight ratio of the untreated hypertensive rats were significantly increased compared to the sham group. These data in the Far groups reduced significantly, but didn’t show dose dependence.When the experiment came to end, ET-1 and Angiotensin-II reached high levels in the model group. After chronic administration of fargesin, ET was lower than that in the model group and angiotensin-II decreased even lower than values in the captopril group. The concentrations of MDA were increased markedly in the hypertensive rats compared with the concentration in the sham rats. The activities of CAT, NOS, GSH-Px and SOD, were significantly decreased in the untreated hypertensive rats compared to the sham rats.Conclusion:These data suggest that fargesin can decrease SBP and improve the cardiac hypertrophy in the 2K1 C hypertensive rats. The mechanism of antihypertensive effect of fargesin is associated with its anti-oxidative actions and promoting NO release. |
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