Günther Ilka, Rimbach Gerald, Nevermann Sandra, Neuhauser Cathrina, Stadlbauer Verena, Schwarzinger Bettina, Schwarzinger Clemens, Ipharraguerre Ignacio R, Weghuber Julian, Lüersen Kai
Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
School of Engineering, University of Applied Sciences Upper Austria, Wels, Austria.
Front Pharmacol. 2021 Dec 15;12:794404. doi: 10.3389/fphar.2021.794404. eCollection 2021.
Medicinal plant extracts are becoming increasingly important as an alternative for traditional drugs against diabetes mellitus (DM). For this reason, we initialized a target-based screening of 111 root extracts from an open access plant extract library (PECKISH) by ascertaining their inhibitory efficacy on α-glucosidase. The two most active extracts L. (roseroot) and L. (avens root) were further tested for their antidiabetic activities in terms of their impact on different regulatory key points of glucose homeostasis. To this end, various enzyme- and cell culture-based assays were employed including the determination of sodium-dependent glucose transporter 1 (SGLT1) activity in Caco-2 monolayers by Ussing chambers and of glucose transporter 4 (GLUT4) translocation in a GFP-reporter cell line. Subsequently, the antidiabetic potential of the root extracts were further evaluated in models, namely hen's eggs test and the fruit fly . Avens root extract was found to be a more potent inhibitor of the enzymes α-glucosidase and dipeptidyl peptidase-4 (DPP4) than roseroot extract. Most importantly, only avens root extract exhibited antidiabetic activity in the two models eliciting a reduced blood glucose level in the model and a decline of the triglyceride level in a dietary starch-induced obesity model. Analyses of the polyphenolic composition of the avens root extract by HPLC revealed a high content of ellagic acid and its derivatives as well as ellagitannins such as pedunculagin, stenophyllanin, stachyurin, casuarinin and gemin A. In conclusion, avens root extract represents a promising medicinal plant that should be considered in further studies on hyperglycemia in laboratory rodents and humans.
药用植物提取物作为传统抗糖尿病药物的替代品正变得越来越重要。因此，我们通过测定111种来自开放获取植物提取物库（PECKISH）的根提取物对α-葡萄糖苷酶的抑制功效，启动了一项基于靶点的筛选。对两种活性最高的提取物——蔷薇根提取物和水杨梅根提取物，进一步测试了它们对葡萄糖稳态不同调控关键点的影响，以评估其抗糖尿病活性。为此，采用了各种基于酶和细胞培养的测定方法，包括使用尤斯灌流小室测定Caco-2单层细胞中钠依赖性葡萄糖转运蛋白1（SGLT1）的活性，以及在绿色荧光蛋白报告细胞系中测定葡萄糖转运蛋白4（GLUT4）的转位。随后，在鸡胚试验和果蝇模型中进一步评估了根提取物的抗糖尿病潜力。结果发现，水杨梅根提取物比蔷薇根提取物对α-葡萄糖苷酶和二肽基肽酶-4（DPP4）的抑制作用更强。最重要的是，只有水杨梅根提取物在这两种模型中表现出抗糖尿病活性，在鸡胚模型中降低了血糖水平，在饮食淀粉诱导的肥胖果蝇模型中降低了甘油三酯水平。通过高效液相色谱法对水杨梅根提取物的多酚成分进行分析，发现其含有高含量的鞣花酸及其衍生物，以及诸如柯里拉京、窄叶水杨梅素、水苏素、桤木素和双聚A等鞣花单宁。总之，水杨梅根提取物是一种有前景的药用植物，在进一步针对实验室啮齿动物和人类高血糖的研究中应予以考虑。
