Integrated transcriptomics and network pharmacology to reveal the mechanism of Physochlainae Radix in the treatment of asthma

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2025-02-06 DOI:10.1016/j.phymed.2025.156470

Jinyan Tan , Jianing Zhang , Weidong Yang , Jianli Li , Yun Zang , Siqi Yang , Yan Liu , Rui Mao , Leilei Xie , Bingyou Yang , Yingli Wang , Yangang Cheng

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Abstract

Background

Physochlainae Radix (PR), a valuable traditional Chinese medicine, has been historically applied for the treatment of bronchitis and asthma in clinic, yet its mechanisms have not been clearly elucidated.

Purpose

This study aims to reveal the underlying mechanisms of PR in treating asthma, employing transcriptomics and network pharmacology approaches.

Methods

To evaluate the therapeutic effects of PR on asthma, we established the asthmatic model in ICR mice by using OVA. Firstly, we employed LC-MS and GNPS to analyze the major chemical constituents in PR. Subsequently, the effects of PR in asthma treatment were assessed through histology, biochemical analysis, and immunofluorescence (IF) assay. Further, an integrated approach of transcriptomics and network pharmacology was applied to identify the target proteins and related pathways of PR against asthma. IF, immunohistochemical (IHC), enzyme-linked immunosorbent assay (ELISA), and western blotting (WB) were utilized for experimental validation and mechanistic studies.

Results

Using UPLC/Q-Orbitrap-MS and GNPS, we eventually identified 23 potential active components from PR. It was discovered for the first time that PR contains a large number of steroidal saponins. PR treatment has been shown to improve lung function, histomorphological changes, and inflammation in the OVA-induced asthma model. According to the results of the transcriptomics and network pharmacology research, PR targeted CXCR2, CCR1, MMP3, MMP9, and IL-17 as crucial elements for treating asthma through the TLR4/MyD88/NF-κB, MAPK, and IL-17 pathways. The key proteins of these pathways were validated by IF and/or WB. Additionally, it was verified that the therapeutic effect of PR on asthmatic mice was related to the inhibition of the activation of the TLR4/MyD88 pathway by introducing TAK-242, an inhibitor of TLR4.

Conclusions

This research revealed that PR improves asthma through the TLR4/MyD88/NF-κB, MAPK, and IL-17 pathways. It is worth noting that this is the first time that transcriptomics and network pharmacology have been comprehensively used to explore the mechanism of PR in treating asthma. This finding advances our understanding of the pharmacological mechanisms underlying PR and lends support to its usage as a treatment agent for asthma.

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整合转录组学和网络药理学揭示青藤治疗哮喘的机制

背景：青霉是临床上治疗支气管炎和哮喘的珍贵中药，但其作用机制尚不清楚。目的利用转录组学和网络药理学方法，揭示PR治疗哮喘的潜在机制。方法采用OVA法建立ICR小鼠哮喘模型，评价其对哮喘的治疗作用。首先，我们采用LC-MS和GNPS分析了PR中的主要化学成分。随后，我们通过组织学、生化分析和免疫荧光（IF）检测来评估PR对哮喘的治疗效果。此外，利用转录组学和网络药理学的综合方法鉴定了PR抗哮喘的靶蛋白和相关途径。采用IF、免疫组织化学（IHC）、酶联免疫吸附试验（ELISA）和western blotting （WB）进行实验验证和机制研究。结果通过UPLC/Q-Orbitrap-MS和GNPS鉴定出了23种潜在有效成分，首次发现其含有大量甾体皂苷。在ova诱导的哮喘模型中，PR治疗已被证明可以改善肺功能、组织形态学改变和炎症。根据转录组学和网络药理学研究结果，PR通过TLR4/MyD88/NF-κB、MAPK和IL-17通路靶向CXCR2、CCR1、MMP3、MMP9和IL-17作为治疗哮喘的关键元件。这些通路的关键蛋白通过IF和/或WB验证。此外，我们还通过引入TLR4抑制剂TAK-242，验证了PR对哮喘小鼠的治疗作用与抑制TLR4/MyD88通路的激活有关。结论PR通过TLR4/MyD88/NF-κB、MAPK、IL-17通路改善哮喘。值得注意的是，这是首次综合运用转录组学和网络药理学来探讨PR治疗哮喘的机制。这一发现促进了我们对PR的药理学机制的理解，并支持其作为哮喘治疗剂的使用。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.