Geniposide from Gardenia jasminoides var. radicans Makino Attenuates Myocardial Injury in Spontaneously Hypertensive Rats via Regulating Apoptotic and Energy Metabolism Signalling Pathway

Abstract

Introduction

Hypertension is closely related to myocardial injury. Long-term hypertension can cause myocardial injury. Therefore, it is very important to find drugs to treat myocardial injury caused by hypertension. The aim of present study is to investigate the effects and mechanisms of geniposide on myocardial injuries in spontaneously hypertensive rats (SHR) and H9c2 cells induced by NaCl solution.

Materials and Methods

Male Wistar–Kyoto (WKY) and SHR rats were given different doses of geniposide (25 mg/kg/d or 50 mg/kg/d) or distilled water for three consecutive weeks. Meanwhile, an H9c2 cell line-injury model was established using a solution of 150 µmol/L NaCl for 8 h. The cardiac function and related indexes of rats were detected.

Results

The results showed that geniposide decreased the levels of COI and COIII, which promoted the phosphorylation of AMPK (p-AMPK) and enhanced the energy metabolism pathway. Geniposide improved myocardial apoptosis by regulating apoptotic proteins (p38, BAX and Bcl-2). Finally, heart function was regulated, and the markers of myocardial injury were decreased. Geniposide increased the viability of H9c2 cells treated with the NaCl solution and decreased the rate of apoptosis by regulating the levels of apoptotic proteins. Geniposide could activate energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and reduce H9c2 cell apoptosis.

Conclusion

Our results showed that the mechanisms by which geniposide improves myocardial injury in SHR may be through regulating the energy metabolism signalling pathway (AMPK/SirT1/FOXO1) and improving myocardial apoptosis by regulating apoptotic proteins.

Keywords:

• geniposide
• SHR
• myocardial injury
• apoptosis
• energy metabolism

Acknowledgments

This work was supported by the National Key Research and Development Project (The Major Project for Research of the Modernization of TCM): Key Technology Research for the Characteristic Chinese Medicine Industry Chain of Rehmannia glutinosa (2019YFC1708802); the Ph.D. Research Funds of Henan University of Chinese Medicine (RSBSJJ2018-04); Major science and technology projects of Henan Province (171100310500); Henan province high-level personnel special support “ZhongYuan One Thousand PeoplePlan”-Zhongyuan Leading Talent (ZYQR201810080); and the project of evaluation,intensive cultivation and demonstration of Henan Local Medicinal Materials (NO.[2016] 149).

Disclosure

The authors declare that they have no conflicts of interest in this work.