State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, China.
Department of Allergy and Clinical Immunology, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.
Biomed Pharmacother. 2022 Jun;150:112957. doi: 10.1016/j.biopha.2022.112957. Epub 2022 Apr 21.
Obesity and metabolic disorders have gradually become public health-threatening problems. The metabolic disorder is a cluster of complex metabolic abnormalities which are featured by dysfunction in glucose and lipid metabolism, and results from the increasing prevalence of visceral obesity. With the core driving factor of insulin resistance, metabolic disorder mainly includes type 2 diabetes mellitus (T2DM), micro and macro-vascular diseases, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and the dysfunction of gut microbiota. Strategies and therapeutic attention are demanded to decrease the high risk of metabolic diseases, from lifestyle changes to drug treatment, especially herbal medicines. Indole is a parent substance of numerous bioactive compounds, and itself can be produced by tryptophan catabolism to stimulate glucagon-like peptide-1 (GLP-1) secretion and inhibit the development of obesity. In addition, in heterocycles drug discovery, the indole scaffold is primarily found in natural compounds with versatile biological activity and plays a prominent role in drug molecules synthesis. In recent decades, plenty of natural or synthesized indole deriviatives have been investigated and elucidated to exert effects on regulating glucose hemeostasis and lipd metabolism. The aim of this review is to trace and emphasize the compounds containing indole scaffold that possess immense potency on preventing metabolic disorders, particularly T2DM, obesity and NAFLD, along with the underlying molecular mechanisms, therefore facilitate a better comprehension of their druggability and application in metabolic diseases.
肥胖和代谢紊乱逐渐成为威胁公众健康的问题。代谢紊乱是一组复杂的代谢异常，其特征是葡萄糖和脂质代谢功能障碍，并且是由内脏肥胖患病率的增加引起的。以胰岛素抵抗为核心驱动因素，代谢紊乱主要包括 2 型糖尿病（T2DM）、微血管和大血管疾病、非酒精性脂肪性肝病（NAFLD）、血脂异常和肠道微生物群功能障碍。需要采取策略和治疗措施来降低代谢疾病的高风险，从生活方式改变到药物治疗，特别是草药。吲哚是许多生物活性化合物的母体物质，本身可以通过色氨酸分解代谢产生，刺激胰高血糖素样肽-1（GLP-1）的分泌并抑制肥胖的发展。此外，在杂环药物发现中，吲哚支架主要存在于具有多种生物活性的天然化合物中，在药物分子合成中起着重要作用。在过去的几十年中，已经研究和阐明了大量的天然或合成的吲哚衍生物，以发挥调节血糖稳态和脂质代谢的作用。本综述的目的是追踪和强调含有吲哚支架的化合物在预防代谢紊乱方面的巨大潜力，特别是 2 型糖尿病、肥胖和非酒精性脂肪性肝病，以及潜在的分子机制，从而更好地理解它们的成药性和在代谢疾病中的应用。
