# Beyond α-Glucosidase and α-Amylase Inhibition: Integrated In Vitro and Multi-Scale In Silico Insights into the Antidiabetic and Antioxidant Mechanisms of Oxalis corniculata L. Aerial Parts

## TL;DR

This study explores how Oxalis corniculata plant parts may help manage diabetes by inhibiting digestive enzymes and offering antioxidant effects, supported by both lab tests and computer simulations.

## Contribution

The study integrates in vitro and multi-scale in silico methods to reveal novel antidiabetic and antioxidant mechanisms of Oxalis corniculata beyond enzyme inhibition.

## Key findings

- The ethyl acetate fraction of Oxalis corniculata showed strong inhibition of α-glucosidase and α-amylase, better than acarbose.
- Molecular docking and simulations confirmed stable interactions with digestive enzymes and antioxidant properties.
- Network pharmacology identified modulation of insulin resistance pathways and redox-related enzymes as key mechanisms.

## Abstract

Diabetes mellitus is a major global health concern associated with severe metabolic and cardiovascular complications. This study evaluated the antidiabetic and antioxidant activities of Oxalis corniculata L. aerial parts, with a focus on α-glucosidase and α-amylase inhibition, using a combination of in vitro assays and in silico analyses. Among the tested fractions, the ethyl acetate fraction exhibited the strongest inhibitory activity against both enzymes, with IC50 values of 0.097 and 0.015 mg/mL for α-glucosidase and α-amylase, respectively, surpassing those of the reference drug, acarbose. This fraction also demonstrated potent antioxidant activity, with IC50 values of 0.025 and 0.020 mg/mL in DPPH and ABTS assays, respectively. To elucidate the underlying mechanisms beyond digestive enzyme inhibition, bioactive constituents were screened and evaluated using network pharmacology, molecular docking, molecular dynamics simulations, and density functional theory (DFT) calculations. Molecular docking and dynamic simulations confirmed stable and energetically favorable interactions with α-glucosidase and α-amylase. Network pharmacology analysis revealed that the antidiabetic effects of O. corniculata involve modulation of insulin resistance-related pathways, particularly PI3K/Akt signaling, GLUT4 translocation, and inflammation-associated targets, alongside regulation of oxidative stress through redox-related enzymes. Complementary DFT analysis provided molecular-level insights into the antioxidant mechanisms, highlighting favorable electronic properties that support efficient radical scavenging. Overall, this integrated experimental–computational study provided valuable evidence of O. corniculata aerial parts as a promising multi-target phytotherapeutic candidate for diabetes management, extending its therapeutic relevance beyond α-glucosidase and α-amylase inhibition.