Tangeretin prevents cardiac failure induced by reperfusion/ischaemia by inhibiting apoptosis, endoplasmic reticulum stress, and JNK/ERK pathway
Yu Liu 1,   Jian Wang 1,   Chuanlei Zhang 1,   Xinran Hou 1,   Yan Kong 1
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Department of Anaesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Submission date: 2020-01-14
Final revision date: 2020-06-02
Acceptance date: 2020-06-04
Online publication date: 2020-07-08
Cardiac diseases constitute the leading cause of human mortality across the globe. The study was conducted to examine the cardiac preventive effects of tangeretin on H9c2 cardiomyocytes.

Material and methods:
Ischaemia/reperfusion was induced in H9c2 cardiomyocytes through anoxygenic conditions. CCK8 was used for estimation of the viability of cardiomyocytes. SOD, CAT, and GSH were determined by biochemical assays. Apoptosis was assessed through DAPI, EdU, and Annexin V/PI staining assays. ROS levels were determined by flow cytometry. The mRNA expression was determined by qRT-PCR, and protein expression was determined by western blotting.

The results showed that tangeretin treatment enhanced the proliferation of ischaemic cardiomyocytes in a time-dependent fashion. The EDU and DAPI staining assays showed that ischaemic cardiomyocytes exhibited lower proliferation rates and higher apoptosis. However, treatment with tangeretin exerted protective effects by inhibiting apoptosis in ischaemic cardiomyocytes. Additionally, annexin V/PI assay showed that tangeretin treatment reduced the percentage of the apoptotic cells in the ischaemic cardiomyocytes. The expression of Bax and caspase-3 were decreased and that of Bcl-2 was increased in ischaemic cardiomyocytes upon tangeretin treatment. The low cytometric analysis showed that tangeretin suppressed the ROS levels in ischaemic cardiomyocytes by increasing the expression of SOD, CAT, and GSH. Finally, tangeretin blocked the JNK/ERK signalling pathway in the ischaemic H9c2 cardiomyocytes.

This study establishes the cardio-protective role of tangeretin and may pave the way for conducting more such studies in the future.