Trigonelline and its impact on insulin resistance: A detailed examination of its pharmacological benefits

A global health concern, insulin resistance (IR) is associated with metabolic diseases like obesity, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus (T2DM). Because of their cost, side effects, and partial efficacy, current therapies frequently fall short. This review aims to critically assess trigonelline (TRG)'s therapeutic potential in treating insulin resistance by analyzing evidence, evaluating its effectiveness in increasing insulin sensitivity, and discussing its advantages over conventional treatments, while also addressing critically research gaps and clinical translation opportunities. A systematic search was performed using scientific databases like PubMed and Scopus to assess the pharmacological benefits of TRG in IR and its metabolic complications. Inclusion and exclusion criteria were applied to select relevant preclinical and clinical studies, ensuring high methodological quality. Coffee and fenugreek contain the natural alkaloid TRG, which has shown promise as a treatment option. The preclinical and clinical data on TRG's contribution to bettering lipid metabolism, glycemic control, and insulin sensitivity (IS) are summarized in this review. TRG works through a variety of mechanisms, such as GLP-1 modulation, PPARγ activation, stimulation of the p38 MAPK/ATF-2 signaling pathway and antioxidant and anti-inflammatory properties. These findings were supported by in silico investigations. Clinical trials are scarce despite encouraging preclinical results, underscoring the need for additional study to confirm TRG's safety and effectiveness in people. The potential of TRG as a fresh, organic remedy is highlighted in this manuscript.