title: Total Flavonoids from Clinopodium chinense (Benth.) O. Ktze Protect against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.
abstract: Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. This study aims to investigate the protective effects of the total flavonoids from Clinopodium chinense (Benth.) O. Ktze (TFCC) against doxorubicin- (DOX-) induced cardiotoxicity. Male rats were intraperitoneally injected with a single dose of DOX (3 mg/kg) every 2 days for three injections. Heart samples were collected 2 weeks after the last DOX dose and then analyzed. DOX delayed body and heart growth and caused cardiac tissue injury, oxidative stress, apoptotic damage, mitochondrial dysfunction, and Bcl-2 expression disturbance. Similar experiments in H9C2 cardiomyocytes showed that doxorubicin reduced cell viability, increased ROS generation and DNA fragmentation, disrupted mitochondrial membrane potential, and induced apoptotic cell death. However, TFCC pretreatment suppressed all of these adverse effects of doxorubicin. Signal transduction studies indicated that TFCC suppressed DOX-induced overexpression of p53 and phosphorylation of JNK, p38, and ERK. Studies with LY294002 (a PI3K/AKT inhibitor) demonstrated that the mechanism of TFCC-induced cardioprotection also involves activation of PI3K/AKT. These findings indicated the potential clinical application of TFCC in preventing DOX-induced cardiac oxidative stress.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, No. 151, North Road Malianwa, Haidian District, Beijing 100094, China.
authors.forename: Rong Chang
authors.initials: RC
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, No. 151, North Road Malianwa, Haidian District, Beijing 100094, China.
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Xu
authors.affiliation: Academy of Forestry, Baishan, Jilin 134302, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhi Liu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, No. 151, North Road Malianwa, Haidian District, Beijing 100094, China.
authors.forename: Gui Bo
authors.initials: GB
authors.lastname: Sun
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, No. 151, North Road Malianwa, Haidian District, Beijing 100094, China.
authors.forename: Yin Di
authors.initials: YD
authors.lastname: Zhu
authors.affiliation: Academy of Chinese Materia Medica, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Dong
authors.affiliation: Harbin University of Commerce, Xuehai Street, Songbei District, Harbin, Heilongjiang 150028, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, China.
authors.forename: Hai Jing
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Academy of Chinese Materia Medica, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, No. 151, North Road Malianwa, Haidian District, Beijing 100094, China.
authors.forename: Xiao Bo
authors.initials: XB
authors.lastname: Sun