研究动态
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青萝抗炎机制的研究。通过调节 TLR4/MyD88/NF-κB 通路:综合网络药理学、血清药物化学和代谢组学。

Investigation into the anti-inflammatory mechanism of Pothos chinensis (Raf.) Merr. by regulating TLR4/MyD88/NF-κB pathway: Integrated network pharmacology, serum pharmacochemistry, and metabolomics.

发表日期:2024 Jul 02
作者: Guanlin Xiao, Minjuan Yang, Zhihao Zeng, Ruiyin Tang, Jieyi Jiang, Guangyin Wu, Canhui Xie, Dezheng Jia, Xiaoli Bi
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

炎症与疾病进展直接相关,并显着增加全球疾病负担。 Pothos chinensis (Raf.) Merr. (PCM) 在中国瑶医学中常用来治疗肿瘤和骨科疾病,如膝骨关节炎和风湿性骨不适。前期研究发现PCM具有显着的抗炎特性,通过血清药物化学、网络药理学和血清代谢组学的综合策略,探讨PCM的活性成分及其抗炎药理机制。分别采用UPLC-QTOF-MS/MS和UPLC对PCM的化学成分进行分析,分析了吸收到血液中的PCM的原型成分。根据吸收到血液成分的特征,利用网络药理学发现了PCM抗炎的潜在靶点和信号通路。此外,使用 UPLC-QTOF-MS/MS 进行的代谢组学研究确定了与 PCM 抗炎作用相关的生物标志物和代谢途径。最后,通过体内和体外实验验证了假设的机制。首次鉴定了PCM中的40种化学成分,并对其中7种化学成分进行了定量分析,同时发现了5种血清迁移原型成分。网络药理学KEGG富集分析显示,花生四烯酸代谢、酪氨酸代谢、TNF信号通路、NF-κB信号通路、苯丙氨酸代谢是PCM抗炎的主要信号通路。药效学结果表明,PCM 可改善肝损伤和炎症细胞浸润,并下调肝脏中 IL-1β、NF-κB p65 和 MyD88 的蛋白表达。代谢组学研究鉴定出53种不同的血清代谢物,主要与嘌呤和嘧啶代谢、苯丙氨酸代谢、初级胆汁酸生物合成和甘油磷脂代谢相关。综合结果表明,PCM的抗炎调节网络与PCM的5个代谢物、3个代谢途径、7个靶点和4个活性成分有关。此外,分子对接鉴定了活性成分与核心靶点之间的结合能力,并通过体外实验验证了活性成分的抗炎功效。我们的研究证明了PCM的抗炎作用,这些发现为对 PCM 抗炎活性成分和代谢机制的新见解。版权所有 © 2024。Elsevier B.V. 出版。
Inflammation is directly related to disease progression and contributes significantly to the global burden of disease. Pothos chinensis (Raf.) Merr. (PCM) is commonly used in Yao medicine in China to treat tumors, and orthopedic illnesses such as knee osteoarthritis, and rheumatic bone discomfort. PCM was found to have significant anti-inflammatory properties in previous studies.To explore the active compounds of PCM and their anti-inflammatory pharmacological mechanisms through an integrated strategy of serum pharmacochemistry, network pharmacology, and serum metabolomics.The qualitative and quantitative analyses of the chemical components of PCM were performed using UPLC-QTOF-MS/MS and UPLC, respectively, and the prototype components of PCM absorbed into the blood were analyzed. Based on the characterized absorbed into blood components, potential targets and signaling pathways of PCM anti-inflammatory were found using network pharmacology. Furthermore, metabolomics studies using UPLC-QTOF-MS/MS identified biomarkers and metabolic pathways related to the anti-inflammatory effects of PCM. Finally, the hypothesized mechanisms were verified by in vivo and in vitro experiments.Forty chemical components from PCM were identified for the first time, and seven of them were quantitatively analyzed, while five serum migratory prototype components were found. Network pharmacology KEGG enrichment analysis revealed that arachidonic acid metabolism, Tyrosine metabolism, TNF signaling pathway, NF-κB signaling pathway, and phenylalanine metabolism were the main signaling pathways of PCM anti-inflammatory. Pharmacodynamic results showed that PCM ameliorated liver injury and inflammatory cell infiltration and downregulated protein expression of IL-1β, NF-κB p65, and MyD88 in the liver. Metabolomics studies identified 53 different serum metabolites, mainly related to purine and pyrimidine metabolism, phenylalanine metabolism, primary bile acid biosynthesis, and glycerophospholipid metabolism. The comprehensive results demonstrated that the anti-inflammatory modulatory network of PCM was related to 5 metabolites, 3 metabolic pathways, 7 targets, and 4 active components of PCM. In addition, molecular docking identified the binding ability between the active ingredients and the core targets, and the anti-inflammatory efficacy of the active ingredients was verified by in vitro experiments.Our study demonstrated the anti-inflammatory effect of PCM, and these findings provide new insights into the active ingredients and metabolic mechanisms of PCM in anti-inflammation.Copyright © 2024. Published by Elsevier B.V.