健脾养血解毒汤通过调节氧化磷酸化的电子传递改善银屑病小鼠的能量代谢。
Jianpi-Yangxue-Jiedu decoction improves the energy metabolism of psoriasis mice by regulating the electron transfer of oxidative phosphorylation.
作者信息
Zhao Ning, Wang YaZhuo, Qu BaoQuan, Zhu HaoYue, Yang DanYang, Zhang XiaWei, Zhao JingXia, Wang Yan, Meng YuJiao, Chen Zhaoxia, Li Ping, Di TingTing
机构信息
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing, People's Republic of China; Capital Medical University, Beijing, 100069, People's Republic of China.
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing, People's Republic of China; Capital Medical University, Beijing, 100069, People's Republic of China.
出版信息
J Ethnopharmacol. 2024 Apr 24;324:117714. doi: 10.1016/j.jep.2024.117714. Epub 2024 Jan 5.
ETHNOPHARMACOLOGICAL RELEVANCE
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.
AIM OF THE STUDY
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.
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSIONS
JPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.
民族药理学相关性
炎症性皮肤病银屑病与免疫相关。健脾养血解毒汤（JPYX）是治疗银屑病的有效药物。然而，JPYX的潜在作用机制尚未阐明。
研究目的
本研究的目的是在高脂饮食背景下探讨JPYX治疗银屑病疗效的潜在机制。
材料与方法
本研究建立了咪喹莫特（IMQ）诱导的银屑病样病变小鼠高脂喂养模型。采用超高效液相色谱-串联质谱（UPLC-MS/MS）检测JPYX的血液成分。运用网络药理学、代谢组学和转录组学方法预测JPYX水煎剂治疗银屑病的机制。
结果
JPYX可抑制炎性细胞因子释放，减少角质形成细胞增殖，提高皮肤、淋巴结和胸腺中调节性T细胞百分比，显著减轻银屑病病变。网络药理学预测白细胞介素-1β（IL-1β）、肿瘤坏死因子（TNF）、信号转导和转录激活因子3（STAT3）及表皮生长因子受体（EGFR）可能是潜在靶点，京都基因与基因组百科全书（KEGG）结果显示磷脂酰肌醇-3激酶-蛋白激酶B-哺乳动物雷帕霉素靶蛋白（PI3K-AKT-mTOR）可能是潜在作用机制。实验数据验证表明JPYX水煎剂显著降低mTOR和AKT磷酸化水平。代谢组学分析显示，氨基酸及其代谢产物、苯及其取代物、醛酮酯类、杂环化合物等是JPYX调节的主要代谢产物。对差异代谢产物进行KEGG富集分析。脂肪酸生物合成、I型聚酮化合物结构、类固醇激素生物合成、不饱和脂肪酸生物合成等。转录组学结果显示JPYX显著调节皮肤发育、角质形成细胞分化和氧化磷酸化。进一步实验数据验证表明JPYX水煎剂显著降低线粒体NADH脱氢酶亚基4（mt-Nd4）、线粒体NADH脱氢酶亚基5（mt-Nd5）、线粒体NADH脱氢酶亚基1（mt-Nd1）、干扰素诱导蛋白205（Ifi205）、干扰素诱导蛋白211（Ifi211）和线粒体ATP合成酶8（mt-Atp8）的mRNA水平。
结论
JPYX可能通过调节脂肪酸代谢途径和氧化磷酸化电子传递改善银屑病。
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