Available online 26 October 2025

Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is a severe condition linked to higher morbidity and mortality. Panax ginseng (PG) possesses renoprotective properties; however, its limited bioavailability restricts its efficacy. Wild-simulated PG (WSG), processed to boost its bioactive components, exhibits improved renoprotective effects.. This research examines PG, bioconverted PG (BPG), and bioconverted WSG (BWG) for their protective roles on I/R induced AKI in mice.

C57BL/6 mice underwent bilateral renal pedicle clamping via a dorsal approach for 30 min to induce ischemia, followed by clamp release and 24 hours of reperfusion. Blood and kidney samples were collected at the end of the reperfusion period. Sham-operated mice underwent identical procedures without vascular clamping. Additionally, hydrogen peroxide (H2O2) induced oxidative stress in HK-2 cells.

The effects of each extract were evaluated. Expression of antioxidant, inflammatory, and apoptotic factors was confirmed using western blotting, immunohistochemistry, and TUNEL assays. Both extracts improved survival of H2O2-treated HK-2 cells and enhanced kidney function, as indicated by reduced BUN and Cr levels. Histopathological analysis showed decreased injury, preserved tubular structure, and reduced inflammation in extract-treated groups. These protective effects were linked to activation of the Nrf2/HO-1 pathway, increasing antioxidant enzymes (CAT, GPX-1, SOD-1) and reducing malondialdehyde (MDA) levels. Additionally, the extracts downregulated pro-inflammatory cytokines (TNF-α, IL-1β), suppressed NF-κB phosphorylation, and lowered Bax/Bcl-2 ratio and Caspase-3 activation, enhancing cell survival.

BPG and BWG remarkably ameliorated I/R-induced AKI through modulation of Nrf2/HO-1/NF-κB/Caspase-3 signaling pathway, with BWG exhibiting more substantial renoprotective effects.

Bioconverted Wild-simulated Ginseng

Ischemic Renal Injury

Nrf2/HO-1/NF-κB/Caspase-3 Signaling

Oxidative Stress

Renoprotection

© 2025 The Korean Society of Ginseng. Publishing services by Elsevier B.V.