Division of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei 112, Taiwan, China.
World J Gastroenterol. 2012 Dec 14;18(46):6809-18. doi: 10.3748/wjg.v18.i46.6809.
To explore the bioactivity of an ethanolic extract of Schizandra arisanensis (SA-Et) and isolated constituents against interleukin-1β and interferon-γ-mediated β cell death and abolition of insulin secretion.
By employing BRIN-BD11 cells, the effects of SA-Et administration on cytokine-mediated cell death and abolition of insulin secretion were evaluated by a viability assay, cell cycle analysis, and insulin assay. The associated gene and protein expressions were also measured. In addition, the bioactivities of several peak compounds collected from the SA-Et were tested against cytokine-mediated β cell death.
Our results revealed that SA-Et dose-dependently ameliorated cytokine-mediated β cell death and apoptosis. Instead of suppressing inducible nitric oxide synthase/nitric oxide cascade or p38MAPK activity, suppression of stress-activated protein kinase/c-Jun NH2-terminal kinase activity appeared to be the target for SA-Et against the cytokine mix. In addition, SA-Et provided some insulinotropic effects which re-activated the abolished insulin exocytosis in cytokine-treated BRIN-BD11 cells. Finally, schiarisanrin A and B isolated from the SA-Et showed a dose-dependent protective effect against cytokine-mediated β cell death.
This is the first report on SA-Et ameliorating cytokine-mediated β cell death and dysfunction via anti-apoptotic and insulinotropic actions.
探讨五味子醇提物(SA-Et)及其分离成分对白细胞介素-1β和干扰素-γ介导的β细胞死亡和胰岛素分泌抑制的生物活性。
采用 BRIN-BD11 细胞,通过活力测定、细胞周期分析和胰岛素测定,评估 SA-Et 给药对细胞因子介导的细胞死亡和胰岛素分泌抑制的影响。还测量了相关基因和蛋白的表达。此外,还测试了从 SA-Et 中收集的几种峰化合物对细胞因子介导的β细胞死亡的生物活性。
我们的结果表明,SA-Et 可剂量依赖性地改善细胞因子介导的β细胞死亡和凋亡。SA-Et 对细胞因子混合物的作用靶点似乎不是抑制诱导型一氧化氮合酶/一氧化氮级联或 p38MAPK 活性,而是抑制应激激活蛋白激酶/c-Jun NH2-末端激酶活性。此外,SA-Et 具有一定的胰岛素促分泌作用,可使细胞因子处理的 BRIN-BD11 细胞中被抑制的胰岛素胞吐作用重新激活。最后,从 SA-Et 中分离得到的五味子甲素 A 和 B 对细胞因子介导的β细胞死亡具有剂量依赖性的保护作用。
这是首次报道 SA-Et 通过抗凋亡和胰岛素促分泌作用改善细胞因子介导的β细胞死亡和功能障碍。