Lee Dahae, Kim Ki Hyun, Lee Jaemin, Hwang Gwi Seo, Lee Hye Lim, Hahm Dae-Hyun, Huh Chang Ki, Lee Sang Cheon, Lee Sanghyun, Kang Ki Sung
School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Department of Integrative Plant Science, Chung-Ang University, Anseong, Korea.
J Pharm Pharmacol. 2017 Jul;69(7):875-883. doi: 10.1111/jphp.12719. Epub 2017 Apr 11.
Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic β-cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study.
The effects of C. japonicum var. maackii and its active component cirsimaritin against streptozotocin (STZ)-induced cytotoxicity were assessed in INS-1 cells. By Western blotting analysis, protein expressions related to apoptosis were evaluated. The involvement of apoptosis was also confirmed with image-based cytometric assay and caspase activity tests.
Cirsium japonicum var. maackii extract and cirsimaritin in non-toxic concentrations improved cell viability to near normal levels and protected INS-1 cells against STZ-induced damage. In addition, cirsimaritin reduced the intracellular oxidative stress induced by STZ. Cirsimaritin effectively suppressed apoptosis in pancreatic β cells by decreasing the activation of caspase-8 and caspase-3, BID and the DNA repair protein poly (ADP-ribose) polymerase (PARP) and increasing anti-apoptotic BCL-2 protein expression.
This study demonstrates the therapeutic potential and action mechanism of cirsimaritin for the prevention and treatment of type 1 diabetes mellitus.
维持葡萄糖稳态对细胞存活至关重要。尽管大蓟（Cirsium japonicum var. maackii）具有多种健康益处，但其对1型糖尿病中胰腺β细胞凋亡的影响及潜在机制仍不清楚，本研究对此进行了实验研究。
在INS-1细胞中评估大蓟及其活性成分蓟苦素对链脲佐菌素（STZ）诱导的细胞毒性的影响。通过蛋白质印迹分析，评估与凋亡相关的蛋白质表达。还通过基于图像的细胞计数分析和半胱天冬酶活性测试来确认凋亡的参与情况。
无毒浓度的大蓟提取物和蓟苦素可将细胞活力提高到接近正常水平，并保护INS-1细胞免受STZ诱导的损伤。此外，蓟苦素降低了STZ诱导的细胞内氧化应激。蓟苦素通过降低半胱天冬酶-8和半胱天冬酶-3、BID以及DNA修复蛋白聚（ADP-核糖）聚合酶（PARP）的激活，并增加抗凋亡BCL-2蛋白表达，有效抑制了胰腺β细胞的凋亡。
本研究证明了蓟苦素在预防和治疗1型糖尿病方面的治疗潜力和作用机制。
