# Eleutheroside E alleviates cisplatin-induced ototoxicity by down-regulating MAPK/NF-κB/NLRP3 signaling pathway and inhibiting cochlear cell pyroptosis

## TL;DR

Eleutheroside E protects against hearing loss caused by cisplatin by reducing inflammation and cell death in the ear.

## Contribution

Eleutheroside E is shown to alleviate cisplatin-induced ototoxicity via the MAPK/NF-κB/NLRP3 pathway and pyroptosis inhibition.

## Key findings

- EE preserves auditory function in mice by reducing cochlear hair cell and SGN damage.
- EE suppresses cisplatin-induced pro-inflammatory responses and pyroptosis.
- EE does not compromise the antitumor efficacy of cisplatin.

## Abstract

Cisplatin is a broad-spectrum anticancer agent. Its main side effect - ototoxicity - may impact the quality of patient’s life. Eleutheroside E (EE), the main active component of Acanthopanax, exhibits antioxidant and anti-inflammatory properties. This study investigates the protective effects of EE against cisplatin-induced ototoxicity and its underlying mechanisms. We use C57BL/6 J mice, the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, and cultured cochlear basement membranes in our experiments. We employ network pharmacology and 4D-FastDIA quantitative proteomic analysis. Our results demonstrate that Cisplatin significantly impairs auditory function in mice. However, EE co-treatment preserves auditory function across most measured frequencies, correlating with reduced damage to cochlear hair cells and spiral ganglion neurons(SGNs). Here, we show that EE attenuates cisplatin-induced pro-inflammatory responses and cellular pyroptosis, possibly via downregulation of the MAPK/NF-κB/NLRP3 signaling pathway. In conclusion, EE may offer a promising strategy for reducing Cisplatin’s ototoxicity without affecting its antitumor efficacy.

Eleutheroside E is a natural compound that protects hearing from cisplatin damage, working by suppressing the MAPK/NF-κB/NLRP3 pathway and pyroptosis. The antitumor efficacy of cisplatin was not reduced under the presented experiment condition.