基于网络药理学分析落新妇干预类风湿性关节炎的作用机制及实验验证

doi:10.5246/jcps.2024.03.020

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (3): 248-257.DOI: 10.5246/jcps.2024.03.020

基于网络药理学分析落新妇干预类风湿性关节炎的作用机制及实验验证

陈莹¹, 应海霞¹, 蔡婷婷², 徐云玲²^,^*()

^1. 浙江金华广福肿瘤医院中药房, 浙江金华 321000
^2. 浙江省中医药研究院/浙江省立同德医院, 天然药物研究所, 浙江杭州 310007

收稿日期:2023-10-25 修回日期:2023-11-28 接受日期:2023-12-27 出版日期:2024-03-31 发布日期:2024-03-31
通讯作者: 徐云玲

Analyzing the mechanism and experimental validation of Astilbe chinensis in the treatment of rheumatoid arthritis through network pharmacology

Ying Chen¹, Haixia Ying¹, Tingting Cai², Yunling Xu²^,^*()

¹ Traditional Chinese Medicine Pharmacy, Jinhua Guangfu Oncology Hospital, Jinhua 321000, Zhejiang, China
² Institute of Natural Medicine Research, Zhejiang Academy of Traditional Chinese Medicine/Tongde Hospital of Zhejiang Province, Hangzhou 310007, Zhejiang, China

Received:2023-10-25 Revised:2023-11-28 Accepted:2023-12-27 Online:2024-03-31 Published:2024-03-31
Contact: Yunling Xu
Supported by:
Natural Science Foundation of Zhejiang Province (Grant No. LQ22H280020).

摘要/Abstract

摘要：

本研究以网络药理学和体外实验相结合的综合策略为基础, 预测落新妇改善风湿性关节炎的可能活性成分与作用机制。首先从文献中获取落新妇的有效化合物, 从DisGeNET、GeneCards和OMIM数据库分别筛选出与RA相关的靶点, 然后构建化合物-靶标网络和蛋白-蛋白相互作用网络, 以预测落新妇可能的关键成分及药物靶点, 最后通过体外实验进行验证。最终筛选出29个潜在活性成分和117个交叉药理靶标, 其关键活性成分可能是落新妇酸、3β-乙酰基齐墩果酸、3β-羟基齐墩果-12-烯-27-酸、4-O-没食子酰岩白菜素和儿茶素, 关键作用靶点可能是AKT1、MMP9、EGFR、CASP3和HSP90AA1; GO富集分析显示信号转导、蛋白水解和细胞凋亡过程的负调控与落新妇治疗RA机制密切相关; KEGG通路分析表明癌症、破骨细胞分化和内分泌抵抗信号通路与落新妇干预RA有关。体外实验表明落新妇提取取物可以抑制巨噬细胞炎症因子NO、TNF-α和IL-6的分泌, 降低诱导型一氧化氮合酶(iNOS)、TNF-α和IL-6在LPS诱导的RAW 264.7细胞中的mRNA表达。本研究增加了中药落新妇及其有效成分抗RA药理作用的新认识, 也为后续研究提供思路与依据。

关键词: 落新妇, 类风湿性关节炎, 网络药理, 抗炎活性

Abstract:

To unravel the active components and potential mechanisms of Astilbe chinensis in treating rheumatoid arthritis (RA), we employed a comprehensive strategy that combined network pharmacology and biological activity verification. Firstly, we identified the relevant compounds in A. chinensis from the literature, and RA-related targets were gathered through DisGeNET, GeneCards, and OMIM databases. Subsequently, compound-target and protein-protein interaction networks were constructed to predict the key compounds and promising protein targets of A. chinensis. Finally, these predictions were validated through in vitro anti-inflammatory activity experiments. A total of 29 potential active compounds and 117 intersecting pharmacological targets were identified. Among them, key active compounds included 3β,6β-dihydroxy olean-12-en-27-oic acid (astilbic acid), 3β-acetoxyolean-12-en-27-oic acid (3-acetyl oleanolic acid), 3β-hydroxyurs-12-en-27-oic acid, 4-O-galloylbergenin, and (+)/(-)-catechin. Key targets were identified as AKT1, MMP9, EGFR, CASP3, and HSP90AA1. GO enrichment analysis indicated that signal transduction, proteolysis, and negative regulation of the apoptotic process were closely associated with A. chinensis treatment in RA. KEGG pathway analysis indicated that pathways in cancer, osteoclast differentiation, and endocrine resistance might be crucial for A. chinensis intervention in RA. This finding suggested that multiple components in A. chinensis could regulate various signaling pathways and targets, playing preventive and therapeutic roles in RA. In vitro experiments demonstrated that A. chinensis extracts inhibited the secretion of inflammatory factors (NO, TNF-α, and IL-6) and significantly suppressed the expression of inducible nitric oxide synthase (iNOS), IL-6, and TNF-α mRNA in LPS-induced RAW 264.7 cells. Collectively, our findings not only established the theoretical basis for the efficacy of A. chinensis in treating RA but also provided a direction for subsequent research.

Key words: Astilbe chinensis, Rheumatoid arthritis, Network pharmacology, Anti-inflammatory activity

Supporting:

陈莹, 应海霞, 蔡婷婷, 徐云玲. 基于网络药理学分析落新妇干预类风湿性关节炎的作用机制及实验验证[J]. 中国药学(英文版), 2024, 33(3): 248-257.

Ying Chen, Haixia Ying, Tingting Cai, Yunling Xu. Analyzing the mechanism and experimental validation of Astilbe chinensis in the treatment of rheumatoid arthritis through network pharmacology[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(3): 248-257.

图/表 6

Figure 1. (A) Wayne diagram of the active ingredients of A. chinensis and RA; (B) Active ingredient-RA target network.

Figure 2. PPI network.

Figure 3. Enrichment analysis. (A) GO function analysis diagram; (B) KEGG pathway enrichment bubble diagram.

Figure 4. Potential targets and mechanism of A. chinensis in endocrine resistance signaling pathway.

Figure 5. Determination results of nitrite, TNF-α, and IL-6 contents in culture medium in each group. (x ± s, n＝3). ##P < 0.01 vs. the control group, while *P < 0.05 and **P < 0.01 vs. the LPS-treated group.

Figure 6. Inhibitory effect of A. chinensis extracts on iNOS, TNF-α, and IL-6 mRNA expressions in LPS-induced RAW264.7 cells. (x ± s, n＝3). ##P < 0.01 vs. the control group, while *P < 0.05 and **P < 0.01 vs. the LPS-treated group.

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基于网络药理学分析落新妇干预类风湿性关节炎的作用机制及实验验证

Analyzing the mechanism and experimental validation of Astilbe chinensis in the treatment of rheumatoid arthritis through network pharmacology

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