Evaluating the Alpha Glucosidase and Alpha Amylase Inhibiting the Potential of Curcumin with Empagliflozin an in Vitro Approach

Abstract

Diabetes mellitus (DM) is a metabolic disorder that causes chronic hyperglycemia due to insulin deficiency or resistance. Post-prandial hyperglycemia control requires major therapeutic efforts, where ?-amylase and ?-glucosidase are important enzyme targets that play a significant role in the reduction of digestion of carbohydrate and absorption of glucose. Here an in-vitro study was undertaken to test the inhibition of ?-amylase and ?-glucosidase by a natural polyphenolic curcumin and synthetic SGLT2 inhibitor Empagliflozin, alone and in combination. Inhibition assays of enzyme were conducted with starch and maltose as substrates, whose absorbance was read at 540 nm on a UV–Visible spectrophotometer. The combination of Curcumin and Empagliflozin synergistically enhanced anti-amylase (IC?? = 96.4 ?g/mL) and anti-glucosidase (IC?? = 84.3 ?g/mL) activities compared with their individual potency for both ?-amylase (Curcumin IC?? =142.6 ?g/mL and Empagliflozin IC??=167.3 µM ) as well as for ?-glucosidase inhibition ( namely, Curcumin IC50=121.5 µM; Empagliflozin IC50=156.8µM), respectively). Statistical analysis (one-way ANOVA with Tukey’s test) confirmed the favorable combination effect (FIC index < 1, p < 0.05) of the joint action compared to the monotherapy. The findings indicate co-treatment of Curcumin and Empagliflozin may offer an additive/synergistic inhibition over carbohydrate hydrolyzing enzymes in better regulation of postprandial glucose levels. This indicates the usefulness of combining plant mates with synthetic compounds as an adjunctive therapeutic strategy in type 2 DM treatment.

Introduction

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to insufficient or ineffective insulin. Its prevalence is rising globally, with serious complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Postprandial hyperglycemia is a key contributor to Type 2 diabetes (T2DM), making α-amylase and α-glucosidase—enzymes involved in carbohydrate digestion—important therapeutic targets. Inhibiting these enzymes slows carbohydrate breakdown and glucose absorption, reducing blood sugar spikes.

Empagliflozin, an SGLT2 inhibitor, lowers glucose by promoting urinary excretion and may have additive effects when combined with natural bioactive compounds like curcumin, a turmeric-derived polyphenol with antioxidant, anti-inflammatory, and antidiabetic properties. Curcumin can inhibit carbohydrate-hydrolyzing enzymes, modulate insulin signaling, and protect pancreatic β-cells, though its bioavailability is limited.

This study evaluated the in vitro α-amylase and α-glucosidase inhibitory activities of curcumin, empagliflozin, and their combination. Results showed:

• α-Amylase inhibition: Curcumin (IC?? = 142.6 µg/mL) and empagliflozin (IC?? = 167.3 µg/mL) had moderate activity, while the combination (1:1) showed enhanced inhibition (IC?? = 96.4 µg/mL), approaching the standard drug acarbose (IC?? = 78.5 µg/mL).

• α-Glucosidase inhibition: Curcumin (IC?? = 121.5 µg/mL) was more potent than empagliflozin (IC?? = 156.8 µg/mL). Their combination increased efficacy (IC?? = 84.3 µg/mL), close to acarbose (IC?? = 72.6 µg/mL).

Statistical analysis confirmed the combination’s synergistic effect (FIC < 1, p < 0.05).

Conclusion

This current research study demonstrates that both Curcumin and Empagliflozin have considerable inhibitory activity on ?-amylase or ?-glucosidase, key enzymes in carbohydrate transformation. Their combined effect was more potent than either separately, suggesting a synergistic interaction that reduces postprandial hyperglycemia better than either agent acting alone. Since Curcumin is a natural scavenger of oxygen radicals and Empagliflozin a fully certified anti-diabetic drug, the combination could prove doubly advantageous with respect to enzyme inhibition and metabolism regulation. All this while requiring fewer side effects three is significant for transitioning from conventional monotherapies. This result suggests further in-vivo investigation and the development of formulations in order to confirm its kinetic mechanism and provide a basis for development of clinical practice applications as a new adjunct therapy for diabetes control along with existing treatment modes.

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Copyright

Copyright © 2025 Sharadha Markam, Nikhil Singh, Pankaj Kumar Pandey, Parmjeet Kumar, Piyush Verma, Pooja Vishwakarma, Prabhakar Kaushik, Dr. Jagdish C. Rathi . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.