Jianpi-Yangxue-Jiedu decoction improves the energy metabolism of psoriasis mice by regulating the electron transfer of oxidative phosphorylation

银屑病 药理学 小桶 PI3K/AKT/mTOR通路 化学 代谢组学 汤剂 蛋白激酶B 生物化学 医学 磷酸化 细胞凋亡 内科学 免疫学 转录组 基因表达 色谱法 基因
作者
Ning Zhao,YaZhuo Wang,BaoQuan Qu,Honglong Zhu,DanYang Yang,XiaWei Zhang,Jingxia Zhao,Jingxia Zhao,Yujiao Meng,Zhaoxia Chen,Ping Li,Tingting Di
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:324: 117714-117714 被引量:1
标识
DOI:10.1016/j.jep.2024.117714
摘要

The inflammatory skin condition psoriasis is immune-related. The decoction of Jianpi-Yangxue-Jiiedu (JPYX) is a useful medication for psoriasis. However, the underlying mechanics of JPYX have not yet been clarified. The objective of this study was to investigate the mechanism underlying the efficacy of JPYX in the treatment of psoriasis in the context of a high-fat diet. This work generated a high-fat feeding model of imiquimod (IMQ)-induced psoriasis-like lesion mice. The blood composition of JPYX was examined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The mechanism of JPYX decoction for treating psoriasis was predicted using methods of network pharmacology, metabolomics, and transcriptomics. JPYX prevented the release of inflammatory cytokines, decreased keratinocyte proliferation, enhanced the percentage of Treg cells in the skin, lymph nodes, and thymus, and greatly alleviated psoriatic lesions. Network pharmacology predicted that IL-1β, TNF, STAT3, and EGFR may be potential targets, and KEGG results showed that PI3K-AKT-mTOR may be a potential mechanism of action. Verification of experimental data demonstrated that the JPYX decoction dramatically decreased mTOR and AKT phosphorylation. According to metabolomics analysis, amino acids and their metabolites, benzene and its substitutes, aldehyde ketone esters, heterocyclic compounds, etc. were the primary metabolites regulated by JPYX. KEGG enrichment analysis of differential metabolites was performed. Fatty acid biosynthesis, Type I polyketide structures, Steroid hormone biosynthesis, Biosynthesis of unsaturated fatty acid, etc. Transcriptomic results showed that JPYX significantly regulated skin development, keratinocyte differentiation, and oxidative phosphorylation. Further experimental data verification showed that JPYX decoction significantly reduced the mRNA levels of mt-Nd4, mt-Nd5, mt-Nd1, Ifi205, Ifi211, and mt-Atp8. JPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.
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