Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Rhynchophylline alleviates endothelial injury in spontaneously hypertensive rats by regulating PPARÎ³-mediated iron death

Zhidong Zhu, Haiming Shi

Department of Cardiology, Huashan Hospital, Fudan University, Shanghai 200040, China;

For correspondence:- Haiming Shi Email: hm_shi07@163.com Tel:+862152889999

Accepted: 30 January 2023 Published: 28 February 2023

Citation: Zhu Z, Shi H. Rhynchophylline alleviates endothelial injury in spontaneously hypertensive rats by regulating PPARÎ³-mediated iron death. Trop J Pharm Res 2023; 22(2):327-333 doi: 10.4314/tjpr.v22i2.15

© 2023 The authors.
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Abstract

Purpose: To determine the effects of rhynchophylline (Rhy) on the progression of cardiovascular diseases in rats.

Methods: Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR, 7 week old, weighing 180 – 200 g) were used in this study. The rats were divided into WKY, SHR, SHR+ Rhy (30 mg/kg), and SHR+ Rhy (50 mg/kg). WKY rats were used as the normal control group which had free access to distilled water. The rats were then orally administered Rhy (30 and 50 mg/kg daily by gavage). For inhibition of PPARr, T0070907 was given at a dose of 2 mg/kg for 24 h. The blood pressure of control, spontaneously hypertensive rats (SHR), and SHR rhynchophylline (Rhy) rats were measured. While PPARr levels in the hypertensive rats were assessed by Western blot. Cell apoptosis in response to SHR and Rhy were evaluated by TdT-mediated dUTP nick-end labeling (TUNEL) and Western blot assays, whereas oxidative stress and inflammatory response in SHR rats treated with Rhy were determined by enzyme linked immunosorbent assay (ELISA) and Immunoblot assays, respectively.

Results: Rhy decreased hypertension and up-regulated PPARγ in SHR rats (p < 0.01). In addition, Rhy improved SHR endothelial cell apoptosis by inducing PPARγ, and also produced reduction in proinflammatory factor secretion by inducing PPARγ. Furthermore, Rhy mitigated oxidative stress and iron death by inducing PPARγ (p < 0.001).

Conclusion: Rhynchophylline provides a promising method in alleviating endothelial injury in SHR rats by modulating PPARγ-mediated inflammation and oxidative stres. We therefore thought Rhy alleviated endothelial injury and could serve as a promising drug.

Keywords: Endothelial dysfunction, Hypertension, Rhynchophylline (Rhy), Uncaria, PPARÎ³, Oxidative stress