# Zhigancao decoction alleviates Parkinson’s disease via inhibiting TNF/NF-κB and Ras/ERK-mediated neuroinflammation and apoptosis

## TL;DR

Zhigancao decoction helps treat Parkinson’s disease by reducing inflammation and cell death through specific pathways.

## Contribution

ZGCD is shown to target both TNF/NF-κB and Ras/ERK pathways in Parkinson’s disease using a systems pharmacology approach.

## Key findings

- ZGCD improves motor function in Parkinson’s disease mouse models.
- ZGCD protects neurons by inhibiting neuroinflammation and apoptosis.
- Apigenin and bisdemethoxycurcumin are key bioactive compounds in ZGCD.

## Abstract

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons, with neuroinflammation and apoptosis serving as key pathological drivers. In this study, we investigated the traditional herbal formula Zhigancao Decoction (ZGCD) using an integrated strategy that combined network pharmacology prediction, experimental validation in MPTP-induced mouse and MPP+-treated cellular models, and molecular docking simulation. Our results demonstrate that ZGCD alleviates motor deficits and protects dopaminergic neurons by concurrently inhibiting the TNF/NF-κB and Ras/ERK signaling pathways, thereby reducing the release of pro-inflammatory cytokines and markers of apoptosis. In vitro experiments further confirmed that the bioactive components apigenin and bisdemethoxycurcumin contribute to this multi-pathway regulatory effect. This systems pharmacology approach elucidates how ZGCD simultaneously targets interconnected disease-relevant pathways, highlighting its potential as a multi-target therapeutic strategy for neurodegenerative disorders.

•ZGCD ameliorates motor dysfunction in MPTP-induced Parkinson’s disease mice•ZGCD protects dopaminergic neurons by mitigating neuroinflammation and apoptosis•The mechanism involves the dual inhibition of the TNF/NF-κB and Ras/ERK pathways•Active compounds apigenin and bisdemethoxycurcumin contribute to these effects

ZGCD ameliorates motor dysfunction in MPTP-induced Parkinson’s disease mice

ZGCD protects dopaminergic neurons by mitigating neuroinflammation and apoptosis

The mechanism involves the dual inhibition of the TNF/NF-κB and Ras/ERK pathways

Active compounds apigenin and bisdemethoxycurcumin contribute to these effects

Biological sciences; Ethnopharmacology; Phytopharmacy