Integrated analysis of metabolomic and transcriptomic profiling reveals the effect of Buyang Huanwu decoction on Parkinson's disease in mice

Jianran Hu; Ping Li; Hongyan Han; Pengyu Ji; Xin Zhao; Zhuoyu Li

doi:10.1016/j.phymed.2023.154755

Integrated analysis of metabolomic and transcriptomic profiling reveals the effect of Buyang Huanwu decoction on Parkinson's disease in mice

Phytomedicine. 2023 Jun:114:154755. doi: 10.1016/j.phymed.2023.154755. Epub 2023 Mar 13.

Authors

Jianran Hu¹, Ping Li², Hongyan Han², Pengyu Ji¹, Xin Zhao³, Zhuoyu Li⁴

Affiliations

¹ Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China; Department of Biological Science and Technology, Jinzhong University, Jinzhong 030619, China.
² Department of Biological Science and Technology, Jinzhong University, Jinzhong 030619, China.
³ Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
⁴ Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China. Electronic address: lzy@sxu.edu.cn.

PMID: 36948142
DOI: 10.1016/j.phymed.2023.154755

Abstract

Background: Parkinson's disease (PD) is a common, complex, and chronic neurodegenerative disorder involved in multi-system. At present, medicine for PD has many limitations. Buyang Huanwu decoction (BHD), a famous traditional Chinese medicinal (TCM) formulae, is used in the treatment of PD clinically in China. However, the therapeutic mechanism is still unknown.

Purpose: We aimed to explore the pharmacological mechanism of BHD alleviating PD through an integrated liver metabolome and brain transcriptome analysis.

Methods: The mice with PD were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioral tests and immunohistochemistry were used to evaluate the neuroprotective effects of BHD. The non-targeted metabolomics analysis was conducted to profile differentially accumulated metabolites (DAMs) in the liver using a UHPLC-Q-Exactive MS/MS method. The differentially expressed genes (DEGs) in the brain were investigated by transcriptomic analysis on an Illumina sequencing platform. The correlations of DAMs and DEGs were investigated using an integrated metabolomic and transcriptomic approach.

Results: The results of behavioral tests and immunohistochemistry proved the alleviated effects of BHD on PD symptoms. A total of 14 and 36 DAMs were detected in the groups treated with low- (L group) and high-dose (H group) BHD respectively under the positive ion mode. Compared with the PD model group (M group), three enriched pathways including metabolic pathways, ABC transporters, and biosynthesis of amino acids were common in the L and H group. Transcriptomic analysis proved that BHD could regulate the expression of numerous genes, some of which were targeted by Ben-Ldopa such as Creb5, Gm45623, Ccer2, Cd180, Fosl2, Crip3, and Noxred1. Based on the integrated metabolomic and transcriptomic analysis, 7 metabolite-gene pairs were found in four comparisons, including C vs M, M vs P, M vs L, and M vs H, and 6 enriched pathways containing purine metabolism, glycine/serine/threonine metabolism, phenylalanine metabolism, carbon fixation in photosynthetic organisms, thiamine metabolism, and ABC transporters were overlapped.

Conclusions: Though the underlying pharmacological mechanism of BHD is still lacking, we provided evidence that BHD could improve dopaminergic neurons in MPTP-induced PD mice by regulating liver metabolism and brain transcriptome. The correlation between the liver and the brain was preliminarily revealed in this study.

Keywords: Buyang Huanwu decoction; Integrated analysis; Metabolomic profiling; Parkinson's disease; Transcriptomic profiling.

MeSH terms

Animals
Gene Expression Profiling
Mice
Parkinson Disease*
Tandem Mass Spectrometry
Transcriptome

Substances

buyang huanwu