Drug Design, Development and Therapy (Mar 2021)
Geniposide from Gardenia jasminoides var. radicans Makino Attenuates Myocardial Injury in Spontaneously Hypertensive Rats via Regulating Apoptotic and Energy Metabolism Signalling Pathway
Abstract
Ying Hou,1,* Peipei Yuan,1,* Yang Fu,1 Qi Zhang,1 Liyuan Gao,1 Yaxin Wei,1 Xiaoke Zheng,1,2 Weisheng Feng1,2 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Engineering and Technology Center for Chinese Medicine Development of Henan Province, Henan Science and Technology Department, Zhengzhou, 450046, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoke Zheng; Weisheng FengCollege of Pharmacy, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, 450046, People’s Republic of ChinaTel +86-371-6019-0296Email [email protected]; [email protected]: 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
