The Second Clinical Medical College, and Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
The Second Clinical Medical College, and Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510006, PR China.
Biomed Pharmacother. 2019 Oct;118:109232. doi: 10.1016/j.biopha.2019.109232. Epub 2019 Jul 29.
Triptolide(T9) is a predominant bioactive component extracted from Chinese herb Tripterygium wilfordii Hook F. (TwHF), and has multiple pharmacological activities, such as immunosuppressive and anti-inflammatory activities, et al. However, severe adverse effects and toxicity, particularly nephrotoxicity, limit its clinical application. It has been demonstrated that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway could alleviate T9-induced nephrocyte damage. The aim of this study was to investigate the potential protective role of triptriolide (T11) against T9-induced nephrocyte apoptosis in vitro and in vivo. Renal injury models were established in human kidney 2 (HK2) cells and BALB/c mice using T9, and the protective effects of T11 were probed in vitro and in vivo, respectively. T9 induced nephrocyte damage in HK2 cells and BALB/c mice by induction of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA) and glutathione (GSH) and reduction of superoxide dismutase (SOD), which resulted in the apoptosis of nephrocyte and injury of renal function. While, pretreatment of T11 effectively reversed these changes, resulting in the obvious decrease of oxidative stress and renal function parameters, ameliorated nephrocyte apoptosis, improved cell morphology, and higher increase of Nrf2, NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) protein levels in vitro and in vivo. Altogether, T11 protected against T9-induced nephrocyte apoptosis possibly via suppressing oxidative stress.
雷公藤红素（T9）是从中国草药雷公藤（TwHF）中提取的主要生物活性成分，具有多种药理活性，如免疫抑制和抗炎活性等。然而，严重的不良反应和毒性，特别是肾毒性，限制了其临床应用。已经证明，核因子红细胞 2 相关因子 2（Nrf2）信号通路的激活可以减轻 T9 诱导的肾细胞损伤。本研究旨在探讨三萜内酯（T11）在体外和体内对 T9 诱导的肾细胞凋亡的潜在保护作用。在人肾 2（HK2）细胞和 BALB/c 小鼠中使用 T9 建立肾损伤模型，并分别在体外和体内研究 T11 的保护作用。T9 通过诱导活性氧（ROS）、乳酸脱氢酶（LDH）、丙二醛（MDA）和谷胱甘肽（GSH）以及降低超氧化物歧化酶（SOD）来诱导肾细胞损伤和肾功能损伤，导致肾细胞凋亡。然而，T11 的预处理有效逆转了这些变化，导致氧化应激和肾功能参数明显减少，肾细胞凋亡减轻，细胞形态改善，体外和体内的 Nrf2、NAD(P)H：醌氧化还原酶 1（NQO1）和血红素加氧酶 1（HO-1）蛋白水平升高。总之，T11 通过抑制氧化应激来保护 T9 诱导的肾细胞凋亡。
