# Renoprotective mechanisms of bioconverted wild-simulated ginseng: mitigating oxidative stress, inflammation, and apoptosis to protect against ischemic renal injury via Nrf2/HO-1/NF-κB/caspase-3 signaling

## TL;DR

This study shows that bioconverted wild-simulated ginseng protects against kidney injury by reducing oxidative stress and inflammation through specific signaling pathways.

## Contribution

The study demonstrates that bioconverted wild-simulated ginseng has stronger renoprotective effects than other ginseng forms via Nrf2/HO-1/NF-κB/caspase-3 signaling.

## Key findings

- BWG showed greater renoprotection than BPG and PG in ischemic kidney injury models.
- BWG reduced oxidative stress and inflammation by activating the Nrf2/HO-1 pathway and suppressing NF-κB.
- BWG improved kidney function and cell survival by lowering BUN, Cr, and Caspase-3 activation.

## Abstract

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 inadequate 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 against 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 h 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 the 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, leading to increased expression of antioxidant enzymes (CAT, GPX-1, SOD-1) and reduced malondialdehyde (MDA) levels. Moreover, the extracts downregulated pro-inflammatory cytokines (TNF-α, IL-1β), suppressed NF-κB phosphorylation, decreased 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.

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