1. Academic Validation
  2. BDNF mimetic 7,8-dihydroxyflavone rescues rotenone-induced cytotoxicity in cardiomyocytes by ameliorating mitochondrial dysfunction

BDNF mimetic 7,8-dihydroxyflavone rescues rotenone-induced cytotoxicity in cardiomyocytes by ameliorating mitochondrial dysfunction

  • Free Radic Biol Med. 2023 Feb 8;S0891-5849(23)00055-2. doi: 10.1016/j.freeradbiomed.2023.02.006.
Peng-Zhou Hang 1 Feng-Qin Ge 2 Man-Ru Zhang 3 Qi-Hang Li 2 Hua-Qing Yu 3 Yu-Chen Song 2 Dan-Dan Guo 2 Jing Zhao 4 Hua Zhu 5
Affiliations

Affiliations

  • 1 Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
  • 2 Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; Medical College, Yangzhou University, Yangzhou, 225009, China.
  • 3 Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
  • 4 Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China. Electronic address: zhaojinghmu@163.com.
  • 5 Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China. Electronic address: daitutu990201@163.com.
Abstract

The relationship between mitochondrial dysfunction and Cardiovascular Disease pathogenesis is well recognized. 7,8-Dihydroxyflavone (7,8-DHF), a mimetic of brain-derived neurotrophic factor, inhibits mitochondrial impairments and improves cardiac function. However, the regulatory role of 7,8-DHF in the mitochondrial function of cardiomyocytes is not fully understood. To investigate the potential mito-protective effects of 7,8-DHF in cardiomyocytes, we treated H9c2 or HL-1 cells with the mitochondrial respiratory complex I inhibitor rotenone (Rot) as an in vitro model of mitochondrial dysfunction. We found that 7,8-DHF effectively eliminated various concentrations of Rot-induced cell death and reduced Lactate Dehydrogenase release. 7,8-DHF significantly improved mitochondrial membrane potential and inhibited mitochondrial Reactive Oxygen Species. Moreover, 7,8-DHF decreased routine and leak respiration, restored protein levels of mitochondrial complex I-IV, and increased ATP production in Rot-treated H9c2 cells. The protective role of 7,8-DHF in Rot-induced damage was validated in HL-1 cells. Nuclear phosphorylation protein expression of signal transducer and activator of transcription 3 (STAT3) was significantly increased by 7,8-DHF. The present study suggests that 7,8-DHF rescues Rot-induced cytotoxicity by inhibiting mitochondrial dysfunction and promoting nuclear translocation of p-STAT3 in cardiomyocytes, thus nominating 7,8-DHF as a new pharmacological candidate agent against mitochondrial dysfunction in cardiac diseases.

Keywords

7,8-Dihydroxyflavone; Mitochondrial complex; Rotenone; STAT3.

Figures
Products