Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria Hillcrest 0083, South Africa.
Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Universidad Católica de Murcia, 30107 Murcia, Spain.
Molecules. 2019 Nov 7;24(22):4030. doi: 10.3390/molecules24224030.
Culinary herbs and spices are widely used as a traditional medicine in the treatment of diabetes and its complications, and there are several scientific studies in the literature supporting the use of these medicinal plants. However, there is often a lack of knowledge on the bioactive compounds of these herbs and spices and their mechanisms of action. The aim of this study was to use inverse virtual screening to provide insights into the bioactive compounds of common herbs and spices, and their potential molecular mechanisms of action in the treatment of diabetes. In this study, a library of over 2300 compounds derived from 30 common herbs and spices were screened in silico with the DIA-DB web server against 18 known diabetes drug targets. Over 900 compounds from the herbs and spices library were observed to have potential anti-diabetic activity and liquorice, hops, fennel, rosemary, and fenugreek were observed to be particularly enriched with potential anti-diabetic compounds. A large percentage of the compounds were observed to be potential polypharmacological agents regulating three or more anti-diabetic drug targets and included compounds such as achillin B from yarrow, asparasaponin I from fenugreek, bisdemethoxycurcumin from turmeric, carlinoside from lemongrass, cinnamtannin B1 from cinnamon, crocin from saffron and glabridin from liquorice. The major targets identified for the herbs and spices compounds were dipeptidyl peptidase-4 (DPP4), intestinal maltase-glucoamylase (MGAM), liver receptor homolog-1 (NR5A2), pancreatic alpha-amylase (AM2A), peroxisome proliferator-activated receptor alpha (PPARA), protein tyrosine phosphatase non-receptor type 9 (PTPN9), and retinol binding protein-4 (RBP4) with over 250 compounds observed to be potential inhibitors of these particular protein targets. Only bay leaves, liquorice and thyme were found to contain compounds that could potentially regulate all 18 protein targets followed by black pepper, cumin, dill, hops and marjoram with 17 protein targets. In most cases more than one compound within a given plant could potentially regulate a particular protein target. It was observed that through this multi-compound-multi target regulation of these specific protein targets that the major anti-diabetic effects of reduced hyperglycemia and hyperlipidemia of the herbs and spices could be explained. The results of this study, taken together with the known scientific literature, indicated that the anti-diabetic potential of common culinary herbs and spices was the result of the collective action of more than one bioactive compound regulating and restoring several dysregulated and interconnected diabetic biological processes.
烹饪香草和香料被广泛用作治疗糖尿病及其并发症的传统药物，文献中有多项科学研究支持这些药用植物的使用。然而，人们通常对这些草药和香料的生物活性化合物及其作用机制知之甚少。本研究旨在使用反向虚拟筛选为常见香草和香料的生物活性化合物提供深入了解，并探讨它们在糖尿病治疗中的潜在分子机制。在这项研究中，使用 DIA-DB 网络服务器对 18 种已知的糖尿病药物靶点对源自 30 种常见香草和香料的超过 2300 种化合物进行了计算机筛选。观察到草药和香料库中的 900 多种化合物具有潜在的抗糖尿病活性，甘草、啤酒花、茴香、迷迭香和胡芦巴尤为富含潜在的抗糖尿病化合物。观察到很大一部分化合物可能是调节三个或更多抗糖尿病药物靶点的多效性药物，其中包括来自蓍草的 Achillin B、来自胡芦巴的 asparasaponin I、来自姜黄的双去甲氧基姜黄素、来自柠檬草的 carlinoside、来自肉桂的肉桂单宁 B1、来自藏红花的藏红花酸和来自甘草的甘草素。鉴定出的主要靶标为二肽基肽酶 4 (DPP4)、肠麦芽糖酶-葡糖苷酶 (MGAM)、肝受体同源物-1 (NR5A2)、胰腺α-淀粉酶 (AM2A)、过氧化物酶体增殖物激活受体α (PPARA)、蛋白酪氨酸磷酸酶非受体型 9 (PTPN9)和视黄醇结合蛋白-4 (RBP4)，观察到超过 250 种化合物可能是这些特定蛋白质靶标的抑制剂。只有月桂叶、甘草和百里香被发现含有可能调节所有 18 种蛋白质靶标的化合物，其次是黑胡椒、孜然、莳萝、啤酒花和马郁兰，含有 17 种蛋白质靶标。在大多数情况下，一种植物内的一种以上化合物可能潜在地调节特定的蛋白质靶标。研究观察到，通过对这些特定蛋白质靶标的多化合物-多靶点调节，可以解释这些草药和香料降低高血糖和高血脂的主要抗糖尿病作用。将本研究结果与已知的科学文献结合起来，表明常见烹饪香草和香料的抗糖尿病潜力是多种生物活性化合物共同作用的结果，这些化合物调节和恢复了几个失调和相互关联的糖尿病生物学过程。
