Himpe Eddy, Cunha Daniel A, Song Imane, Bugliani Marco, Marchetti Piero, Cnop Miriam, Bouwens Luc
Cell Differentiation Lab, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), Brussels, Belgium.
PLoS One. 2016 Jun 14;11(6):e0157604. doi: 10.1371/journal.pone.0157604. eCollection 2016.
Previous studies demonstrated that a phenylpropenoic acid glucoside (PPAG) from rooibos (Aspalathus linearis) extract had anti-hyperglycemic activity and significant protective effects on the pancreatic beta cell mass in a chronic diet-induced diabetes model. The present study evaluated the cytoprotective effect of the phytochemical on beta cells exposed to acute cell stress.
Synthetically prepared PPAG was administered orally in mice treated with a single dose of streptozotocin to acutely induce beta cell death and hyperglycemia. Its effect was assessed on beta cell mass, proliferation and apoptotic cell death. Its cytoprotective effect was also studied in vitro on INS-1E beta cells and on human pancreatic islet cells.
Treatment with the phytochemical PPAG protected beta cells during the first days after the insult against apoptotic cell death, as evidenced by TUNEL staining, and prevented loss of expression of anti-apoptotic protein BCL2 in vivo. In vitro, PPAG protected INS-1E beta cells from streptozotocin-induced apoptosis and necrosis in a BCL2-dependent and independent way, respectively, depending on glucose concentration. PPAG also protected human pancreatic islet cells against the cytotoxic action of the fatty acid palmitate.
These findings show the potential use of PPAG as phytomedicine which protects the beta cell mass exposed to acute diabetogenic stress.
先前的研究表明,来自南非红叶茶(Aspalathus linearis)提取物的一种苯丙烯酰葡萄糖苷(PPAG)具有抗高血糖活性,并且在慢性饮食诱导的糖尿病模型中对胰腺β细胞群具有显著的保护作用。本研究评估了这种植物化学物质对暴露于急性细胞应激的β细胞的细胞保护作用。
将合成制备的PPAG口服给予用单剂量链脲佐菌素处理的小鼠,以急性诱导β细胞死亡和高血糖症。评估其对β细胞群、增殖和凋亡性细胞死亡的影响。还在体外对INS-1Eβ细胞和人胰岛细胞研究了其细胞保护作用。
植物化学物质PPAG处理在损伤后的头几天保护β细胞免受凋亡性细胞死亡,TUNEL染色证明了这一点,并且在体内防止了抗凋亡蛋白BCL2表达的丧失。在体外,PPAG分别以依赖BCL2和不依赖BCL2的方式保护INS-1Eβ细胞免受链脲佐菌素诱导的凋亡和坏死,这取决于葡萄糖浓度。PPAG还保护人胰岛细胞免受脂肪酸棕榈酸酯的细胞毒性作用。
这些发现表明PPAG作为植物药具有潜在用途,可保护暴露于急性致糖尿病应激的β细胞群。