Abstract
Fenugreek (Trigonella foenum-graecum) is a widely grown dietary herb in Asia, and its seeds are traditionally used for several diseases, including diabetes. The seeds and leaves possess a variety of compounds that play an important role in regulating their hypoglycemic effect. However, so far, no extensive systematic review exists on its antidiabetic effect, highlighting the molecular mechanisms and isolated compounds. The purpose of this review is to summarize the preclinical and clinical antidiabetic properties of fenugreek and its isolated compounds by focusing on underlying mechanisms. PubMed, Google Scholar, Science Direct, and Scopus databases were searched to retrieve articles until June, 2024. Preclinical studies demonstrated that the antidiabetic effect of fenugreek was mostly associated with enhanced glucose transporter type-4 (GLUT4) translocation and hexokinase activity, decreased glucose-6-phosphatase and fructose-1,6-bisphosphatase activities, inhibited α-amylase and maltase activities, protected β cells, and increased insulin release. Furthermore, few studies have reported its role as a glucagon-like peptide-1 (GLP-1) modulator, 5'-AMP-activated kinase (AMPK) activator, and dipeptidyl peptidase-IV (DPP-IV) inhibitor. Further clinical trials showed that fenugreek seeds improved blood glucose levels, insulin resistance, insulin sensitivity, and lipid profiles. This study highlights significant evidence of the antidiabetic effect of fenugreek and its isolated compounds; therefore, it could be a potential therapy for diabetes.