Cycloastragenol targets Fpr2 to inhibit the TLR4/NF-κB signaling pathway and alleviate neuroinflammation in Parkinson's disease

Abstract

Background

Parkinson's disease (PD) is a neurodegenerative disease, and neuroinflammation is an important factor in its pathogenesis. Therefore, improving neuroinflammation has become a key direction in PD research. Cycloastragenol (CAG) is one of the active ingredients in Astragalus membranaceus, which has pharmacological activities such as anti-inflammatory, antioxidant, and neuroprotective effects. However, there are few reports on its pharmacological effects on PD. Therefore, it is necessary to comprehensively evaluate the pharmacological effects of CAG on PD and elucidate the potential mechanisms of action, providing new ideas for drug development in PD.

Objective

To comprehensively and systematically evaluate the pharmacological effects of CAG on PD and reveal its potential mechanisms of action.

Research design and methods

Firstly, the pharmacological effects of CAG on cell viability, cytotoxicity, behavior, and pathology were evaluated using PD in vitro (MPP⁺ induced SH-SY5Y cells) and in vivo models (MPTP induced mouse model). Furthermore, potential targets and signaling pathways will be screened based on metabolomics and transcriptomics. Ultimately, the connection between the target and the signaling pathway will be validated to elucidate the potential mechanism by which CAG exerts its effects.

Result

CAG can significantly improve the behavioral indicators of PD mice, enhance neuronal vitality, and improve neuroinflammatory levels by inhibiting the expression of inflammatory factors. In addition, CAG can target and activate the expression of Fpr2, thereby regulating the TLR4/NF-κB signaling pathway and promoting the resolution of inflammation.