Effect of Betulinic Acid on Diabetes and its Associated Complications: An Experimental Study

Introduction: Diabetes Mellitus (DM) is a metabolic disease characterised by elevated blood sugar levels and associated complications, such as inflammation, oxidative stress and tissue damage. Betulinic Acid (BA), a naturally occurring pentacyclic triterpene, has demonstrated potential medicinal benefits, such as anti-inflammatory and antioxidant qualities. Hence, it may be useful to explore BA for its antidiabetic activity. Aim: To assess the impact of BA on diabetes and its related complications using in-vitro enzyme inhibitory assays and a cell line model. Materials and Methods: This experimental study was conducted at the Centre for Global Health Research, Saveetha Medical College and Hospitals, Chennai, Tamil Nadu, India from May 2024 to June 2024. In-vitro enzyme inhibitory assays, such as α-amylase inhibition, α-glucosidase inhibition, Aldose Reductase (AR) inhibition and Advanced Glycation End product (AGE) assays, were performed. A cellular glucose uptake assay was conducted using L6 rat skeletal muscle cells with fluorescent 2-NBDG and glucose. Results: The results demonstrated significant inhibition of carbohydrate-hydrolysing enzymes. The percentage inhibition of α-amylase and α-glucosidase ranged from 0.92±0.02% to 67.64±0.06% and from 7.90±0.02% to 74.02±0.05%, respectively, for BA concentrations ranging from 5 to 100 μM. BA exhibited 71.28±0.06% inhibition of AGE compared to aminoguanidine, which showed 79.24±0.07% inhibition at 100 μM. BA also demonstrated 69.97±0.04% inhibition of AR activity compared to metformin, which showed 76.75±0.05% inhibition at 100 μM. Furthermore, BA increased glucose uptake in a dosedependent manner, with the 92 μM concentration exhibiting a glucose uptake of 75.32±0.73 compared to metformin. Through increased cellular glucose absorption in-vitro, BA showed strong antidiabetic efficacy. Conclusion: BA demonstrates promising potential as a therapeutic agent for the management of diabetes. Its ability to boost glucose absorption and reduce oxidative stress suggests that it may help improve insulin sensitivity and halt the progression of diabetes-related complications.