Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China.
Department of Pharmacy, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Dokl Biochem Biophys. 2023 Aug;511(1):156-161. doi: 10.1134/S1607672923600057.
Tripterine (TP, also called celastrol), a pentacyclic triterpene extracted from Tripterygium wilfordii, has beneficial effects on multiple diseases, including obesity and diabetes. However, the effects of TP on β‑cell lipotoxicity have not been fully explored. Here, we found that TP modulated β-cell lipotoxicity in a concentration-dependent and bidirectional manner. At low concentrations, TP potentially protected MIN6 β-cells from palmitate (PA)-induced lipotoxicity. At high concentrations, TP significantly promoted β-cell lipotoxicity, further reinforcing PA-induced cell apoptosis. Furthermore, low-concentration TP inhibited the PA-induced increase in reactive oxygen species (ROS) levels, and its protective effects were abolished by the ROS inducer tert-butyl hydroperoxide. Conversely, high-concentration TP significantly exacerbated the PA-triggered ROS generation, and its enhanced cytotoxicity was partially reversed by the ROS inhibitor N-acetyl-L-cysteine. Thus, TP plays a dual role in β-cell lipotoxicity, suggesting that care should be taken when it is used for obesity and diabetes treatment.
雷公藤红素（TP，也称为 celastrol）是从雷公藤中提取的五环三萜类化合物，对多种疾病（包括肥胖和糖尿病）具有有益作用。然而，TP 对β细胞脂毒性的影响尚未得到充分探索。在这里，我们发现 TP 以浓度依赖和双向的方式调节β细胞脂毒性。在低浓度下，TP 可能保护 MIN6 β细胞免受棕榈酸（PA）诱导的脂毒性。在高浓度下，TP 显著促进β细胞脂毒性，进一步增强 PA 诱导的细胞凋亡。此外，低浓度的 TP 抑制 PA 诱导的活性氧（ROS）水平升高，而 ROS 诱导剂叔丁基过氧化氢可消除其保护作用。相反，高浓度的 TP 显著加剧 PA 引发的 ROS 生成，而 ROS 抑制剂 N-乙酰-L-半胱氨酸部分逆转了其增强的细胞毒性。因此，TP 在β细胞脂毒性中起双重作用，提示在用于肥胖和糖尿病治疗时应谨慎使用。
