Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.
Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
Molecules. 2022 Mar 24;27(7):2102. doi: 10.3390/molecules27072102.
Carnosic acid (CA), a natural polyphenolic diterpene derived from , has been proven to possess a broad spectrum of medicinal properties. Nevertheless, no studies on its impact on pancreatic β-cells have been conducted to date. Herein, clonal rat INS-1 (832/13) cells were pretreated with CA for 24 h and then incubated with streptozotocin (STZ) for 3 h. Several functional experiments were performed to determine the effect of CA on STZ-induced pancreatic β-cell damage, including cell viability assay, apoptosis analysis, and measurement of the level of insulin secretion, glucose uptake, malondialdehyde (MDA), reactive oxygen species (ROS), and proteins expression. STZ treatment decreased cell survival, insulin secretion, glucose uptake, and increased apoptosis, MDA, and ROS production in INS-1 cells. Furthermore, protein expression/phosphorylation analysis showed significant down-regulation in insulin, PDX-1, PI3K, AKT/p-AKT, and Bcl. On the other hand, expression of BAX and BAD and cleaved PARP were significantly increased. Interestingly, preincubation with CA reversed the adverse impact of STZ at the cellular and protein expression levels. In conclusion, the data indicate that CA protects β-cells against STZ-induced damage, presumably through its modulatory effect on the different pathways, including the Pi3K/AKT/PDX-1/insulin pathway and mitochondria-mediated apoptosis.
迷迭香酸（CA）是一种天然多酚二萜类化合物，来源于 ，已被证明具有广泛的药用特性。然而，迄今为止，尚无研究探讨其对胰腺β细胞的影响。在此，用 CA 预处理克隆大鼠 INS-1（832/13）细胞 24 h，然后用链脲佐菌素（STZ）孵育 3 h。进行了几项功能实验来确定 CA 对 STZ 诱导的胰腺β细胞损伤的影响，包括细胞活力测定、细胞凋亡分析以及胰岛素分泌、葡萄糖摄取、丙二醛（MDA）、活性氧（ROS）和蛋白质表达水平的测定。STZ 处理降低了 INS-1 细胞的存活率、胰岛素分泌、葡萄糖摄取，并增加了细胞凋亡、MDA 和 ROS 的产生。此外，蛋白表达/磷酸化分析显示胰岛素、PDX-1、PI3K、AKT/p-AKT 和 Bcl 的表达显著下调。另一方面，BAX 和 BAD 的表达和 PARP 的裂解明显增加。有趣的是，CA 的预孵育在细胞和蛋白表达水平上逆转了 STZ 的不良影响。总之，数据表明 CA 可保护β细胞免受 STZ 诱导的损伤，这可能是通过其对不同途径的调节作用实现的，包括 Pi3K/AKT/PDX-1/胰岛素途径和线粒体介导的细胞凋亡。
