Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo 11562, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Science and Arts (MSA), Cairo 12566, Egypt.
Molecules. 2018 Dec 15;23(12):3334. doi: 10.3390/molecules23123334.
Diabetes mellitus (DM) is a chronic metabolic disease with high morbimortality rates. DM has two types: type 1, which is often associated with a total destruction of pancreatic beta cells, and non-insulin-dependent or type 2 diabetes mellitus (T2DM), more closely associated with obesity and old age. The main causes of T2DM are insulin resistance and/or inadequate insulin secretion. Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in T2DM, as its overexpression may induce insulin resistance. Thus, since PTP1B may be a therapeutic target for both T2DM and obesity, the search for novel and promising natural inhibitors has gained much attention. Hence, several marine organisms, including macro and microalgae, sponges, marine invertebrates, sea urchins, seaweeds, soft corals, lichens, and sea grasses, have been recently evaluated as potential drug sources. This review provides an overview of the role of PTP1B in T2DM insulin signaling and treatment, and highlights the recent findings of several compounds and extracts derived from marine organisms and their relevance as upcoming PTP1B inhibitors. In this systematic literature review, more than 60 marine-derived metabolites exhibiting PTP1B inhibitory activity are listed. Their chemical classes, structural features, relative PTP1B inhibitory potency (assessed by IC values), and structure⁻activity relationships (SARs) that could be drawn from the available data are discussed. The upcoming challenge in the field of marine research-metabolomics-is also addressed.
糖尿病（DM）是一种具有高病死率的慢性代谢疾病。DM 有两种类型：1 型，常与胰腺β细胞的完全破坏有关；以及 2 型糖尿病（T2DM），与肥胖和老年更为密切相关。T2DM 的主要原因是胰岛素抵抗和/或胰岛素分泌不足。蛋白酪氨酸磷酸酶 1B（PTP1B）负调节胰岛素信号通路，在 T2DM 中发挥重要作用，因为其过表达可能会导致胰岛素抵抗。因此，由于 PTP1B 可能是 T2DM 和肥胖症的治疗靶点，因此寻找新型有前途的天然抑制剂已引起广泛关注。因此，最近已经评估了几种海洋生物，包括大型和微型藻类、海绵、海洋无脊椎动物、海胆、海藻、软珊瑚、地衣和海草，作为潜在的药物来源。本文综述了 PTP1B 在 T2DM 胰岛素信号转导和治疗中的作用，并强调了最近从海洋生物中获得的几种化合物和提取物的发现，及其作为新型 PTP1B 抑制剂的相关性。在这项系统的文献综述中，列出了超过 60 种具有 PTP1B 抑制活性的海洋衍生代谢物。讨论了它们的化学类别、结构特征、相对 PTP1B 抑制活性（通过 IC 值评估）以及从现有数据中得出的结构-活性关系（SARs）。还讨论了海洋研究代谢组学领域即将面临的挑战。
