Bauhinia championii Flavone Attenuates Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes by Improving Mitochondrial Dysfunction.
This study aimed to determine the effects ofBauhinia championiiflavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation. Cell viability was detected by CCK-8 assay. Apoptotic rate was measured by Annexin V/PI staining. Levels of mitochondria-associated ROS, mitochondrial transmembrane potential (∆Ψm) and mitochondrial permeability transition pores (MPTP) opening were assessed by fluorescent probes. ATP production was measured by ATP assay kit. The release of cytochrome c, translocation of Bax, and related proteins were measured by western blotting. Our results showed that pretreatment with BCF significantly improved cell viability and attenuated the cardiomyocyte apoptosis caused by H/R. Furthermore, BCF increased ATP production and inhibited ROS-generating mitochondria, depolarization of ΔΨm, and MPTP opening. Moreover, BCF pretreatment decreased Bax mitochondrial translocation, cytochrome c release, and activation of caspase-3, as well as increased the expression of p-PI3K, p-Akt, and the ratio of Bcl-2 to Bax. Interestingly, a specific inhibitor of phosphatidylinositol 3-kinase, LY294002, partly reversed the anti-apoptotic effect of BCF. These observations indicated that BCF pretreatment attenuates H/R-induced myocardial apoptosis strength by improving mitochondrial dysfunction via PI3K/Akt signaling pathway.
Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin 541004, Guangxi, China. liaoping555@163.com.
Ping
P
Liao
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. sunguibo@126.com.
Guibo
G
Sun
Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin 541004, Guangxi, China. 15807731320@163.com.
Chan
C
Zhang
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. lily_12506053@163.com.
Min
M
Wang
Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin 541004, Guangxi, China. sandysun318@163.com.
Yao
Y
Sun
Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin 541004, Guangxi, China. yuehanzhou2012@163.com.
Yuehan
Y
Zhou
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. sunsubmit@163.com.
Xiaobo
X
Sun
Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin 541004, Guangxi, China. jianjielucky@aliyun.com.
Jie
J
Jian
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D036481:Bauhinia / Q000737:chemistry*; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D047309:Flavones; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D010100:Oxygen
Bauhinia championii flavone; PI3K/Akt; apoptosis; hypoxia-reoxygenation; mitochondrial dysfunction