# Magnolol Ameliorates Cisplatin-Induced Acute Kidney Injury with Activation of Nrf2-Associated Antioxidant Responses

## TL;DR

Magnolol protects against kidney damage caused by cisplatin chemotherapy by reducing inflammation and boosting antioxidant defenses.

## Contribution

This study demonstrates magnolol's renoprotective effects in a mouse model of cisplatin-induced acute kidney injury through multiple molecular mechanisms.

## Key findings

- Magnolol reduced serum markers of kidney injury like blood urea nitrogen and creatinine.
- It inhibited inflammation, endoplasmic reticulum stress, and cell death in kidney tissues.
- Magnolol activated Nrf2, enhancing antioxidant responses to protect against cisplatin toxicity.

## Abstract

Cisplatin (CDDP) is a cornerstone chemotherapeutic drug, yet its efficacy is frequently compromised by renal toxicity, primarily manifesting as acute kidney injury (AKI). Magnolol (MG) is a polyphenol from Magnolia officinalis and has been widely documented for its pronounced antioxidant and anti-inflammatory properties. This study evaluated the renoprotective effects of MG in a murine model of CDDP-induced AKI. Male C57BL/6 mice received MG (20 mg/kg) via daily intraperitoneal injection for four consecutive days, starting one day before a single CDDP injection. MG significantly reduced the serum concentrations of blood urea nitrogen and creatinine. Histopathological assessment revealed attenuated tubular damage and reduced expression of tubular injury markers. MG inhibited pro-inflammatory cytokines at both systemic and renal levels, alleviated endoplasmic reticulum stress, and suppressed activation of mitogen-activated protein kinase signaling pathways. Apoptotic damage was mitigated, as shown by the fewer TUNEL-positive cells and lowered expression of pro-apoptotic markers. In parallel, ferroptotic processes were alleviated through downregulation of pro-ferroptotic proteins and preservation of key antioxidant regulators. Importantly, MG restored nuclear factor erythroid 2-related factor 2 activity and upregulated downstream antioxidant effectors. These findings highlight the multi-targeted renoprotective actions of MG and support its possible utility as a therapeutic agent to prevent CDDP-induced renal injury.