Update of Indoles: Promising molecules for ameliorating metabolic diseases

• Published in: Biomedicine & pharmacotherapy Vol. 150; p. 112957
• Main Authors: Hu, Wei, Yan, Guanyu, Ding, Qian, Cai, Jianghong, Zhang, Zhongyi, Zhao, Ziming, Lei, Heping, Zhu, Yi Zhun
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2022; Elsevier
• Subjects: Dyslipidemia; Hepatic steatosis; Indole derivatives; Insulin resistance; Obesity; Type 2 diabetes mellitus; FFA; T2DM; DNA-PKcs; NAFLD; MCP-1; DPP-IV; JNK; HFD; NOD-SCID; Dyslipidemia; Type 2 diabetes mellitus; ub; NRF2; UPR; Fasn; STZ; PPX; IL-1b; Obesity; GLP-1; FBPase; ACSL; SGLT2; ASK1; USP2; IAA; DYRK1A; DIM; GP; AhR; PGC-1α; Hepatic steatosis; PPARα; SREBP-1c; SIRT1; NR4A1; AR; PTP1B; FABP4; TNF-α; TRAFs; CPT-1b; I3C; Insulin resistance; Indole derivatives
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112957

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. [Display omitted] •Indole scaffold was introduced in this review as a privileged structure in drug design for alleviating diabetes.•Indole alkaloids have potential in preventing metabolic disorders, including diet-induced obesity and fatty liver disease.•Mechanism studies of antidiabetic synthesized indoles indicated that these molecules act via various targets.