# Anti-Hyperglycemic and Antioxidant Effects of Sclerocarya birrea Leaf Crude Extract and Biosynthesized Silver Nanoparticles In Vitro

## TL;DR

This study explores the use of Sclerocarya birrea leaf extract and silver nanoparticles in managing diabetes-related hyperglycemia and oxidative stress.

## Contribution

The study introduces biosynthesized silver nanoparticles from Sclerocarya birrea as a novel formulation with anti-hyperglycemic and antioxidant properties.

## Key findings

- Sclerocarya birrea leaf extract and silver nanoparticles inhibited key digestive enzymes, showing potential for managing postprandial hyperglycemia.
- Silver nanoparticles provided superior cytoprotection against oxidative stress in kidney cells compared to the leaf extract.
- Neither formulation significantly affected glucose uptake or SGLT1 expression in intestinal cells.

## Abstract

Postprandial hyperglycemia represents a critical therapeutic target in type 2 diabetes mellitus (T2DM), requiring interventions that simultaneously address glycemic dysregulation and oxidative stress. This study evaluated the anti-hyperglycemic and antioxidant properties of Sclerocarya birrea leaf crude extract (CE) and biosynthesized silver nanoparticles (AgNPs). Phytochemical screening, nanoparticle characterization (UV–Vis, XRD, TEM, SEM, DLS, FTIR), enzyme inhibition assays (α-amylase, α-glucosidase, DPP-IV), glucose dynamics in Caco-2 cells, and antioxidant assays (DPPH, total antioxidant capacity, H2O2 cytoprotection) were performed. Phytochemical analysis identified flavonoids, tannins, alkaloids, and terpenoids as major constituents of Sclerocarya birrea leaf extract. AgNPs exhibited spherical morphology (36.8 ± 8.6 nm, n = 100 particles analyzed), face-centered cubic crystallinity (crystallite size: 32.1 nm), and characteristic surface plasmon resonance at 451 nm. Both formulations inhibited α-amylase (CE IC50: 14 µg/mL; AgNPs IC50: 14.07 µg/mL, n = 3) and α-glucosidase (CE IC50: 15.96 µg/mL; AgNPs IC50: 15.82 µg/mL, n = 3), showing substantial inhibition, though less potent than acarbose. Uniquely, AgNPs demonstrated selective DPP-IV inhibition (IC50: 220.5 µg/mL, n = 3, p < 0.001 vs. CE), completely absent in CE. In antioxidant assays, DPPH scavenging potency was comparable between formulations (CE IC50: 23.45 µg/mL; AgNPs IC50: 22.26 µg/mL, n = 3), while CE achieved higher maximal scavenging at the tested concentrations. Conversely, AgNPs provided superior intracellular cytoprotection against H2O2-induced oxidative stress in kidney cells (80.2 ± 2.1% viability at 76 µg/mL vs. CE 69.8 ± 3.4% at 190 µg/mL, n = 3, p < 0.001), representing a 2.5-fold dose advantage. Neither formulation significantly altered glucose uptake or SGLT1 expression in intestinal epithelial cells (p > 0.05, two-way ANOVA, n = 3). These findings establish S. birrea-based formulations, particularly AgNPs, as promising multifunctional candidates for managing postprandial hyperglycemia and oxidative complications in T2DM. They also highlight nanotechnology-enhanced phytomedicine as an innovative therapeutic strategy.