Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells.
Triptolide (TP) is a diterpene triepoxide with variety biological activities, such as anti-inflammatory, anti-cancerogenic, immunomodulatory and pro-apoptotic activities. However, its clinical application was limited by potential toxicity. Quercetin (Que) is a member of flavonoids with anti-oxidant effects. In this study, we aimed to demonstrate the protective effect of Que in TP-induced oxidative stress and decrease of testosterone generation in reproductive damage. Leydig cells were treated with TP (20, 40 and 60 nM), which caused obvious oxidative stress increasing intracellular ROS, decreasing activities and expressions of GPx and SOD. Apoptosis was resulted from depolarization of mitochondrial membrane potential (ΔΨm) and release of cytochrome C (Cyt-C) showing increase of BAX/Bcl-2 ratio, caspase-3 and caspase-9. Treatment of Que (5 μM) prior to triptolide could restore all the TP-induced alteration in a certain dose range indicating that the oxidative stress might be one reason of TP-induced reproductive toxic effect. These results suggest that the compatibility with Que might reduce the TP-induced reproductive toxicity, which provide a probability to extend the usage of TP.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.
Jie
J
Hu
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.
Qinwei
Q
Yu
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.
Fang
F
Zhao
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China; Central Laboratory, General Clinical Research Center, Nanjing First Hospital, Nanjing 210006, PR China.
Jinzi
J
Ji
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, PR China.
Zhenzhou
Z
Jiang
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.
Xin
X
Chen
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.
Peng
P
Gao
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Yuran
Y
Ren
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Shuai
S
Shao
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, PR China. Electronic address: lyzhang@cpu.edu.cn.
Luyong
L
Zhang
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: brookming@163.com.
Ming
M
Yan
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000633:toxicity*; D004852:Epoxy Compounds / Q000633:toxicity; D006801:Humans; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010616:Phenanthrenes / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D020011:Protective Agents; C001899:triptolide; D011794:Quercetin
Apoptosis; Leydig cells; Nrf2; Oxidative stress; Quercetin; Triptolide