Combining Network Pharmacology and Transcriptomics to Investigate the Mechanisms of Yujiang Paidu Decoction in the Treatment of Chronic Rhinosinusitis with Nasal Polyps.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2024-08-27 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S461769

Yujie Li, Yadong Yin, Juan Xiong, Zhipeng Zhang, Linglong Li, Baoshun Zhang, Feng Zhang, Dehong Mao

{"title":"Combining Network Pharmacology and Transcriptomics to Investigate the Mechanisms of Yujiang Paidu Decoction in the Treatment of Chronic Rhinosinusitis with Nasal Polyps.","authors":"Yujie Li, Yadong Yin, Juan Xiong, Zhipeng Zhang, Linglong Li, Baoshun Zhang, Feng Zhang, Dehong Mao","doi":"10.2147/DDDT.S461769","DOIUrl":null,"url":null,"abstract":"Background: Yujiang Paidu Decoction (YJPD) has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear.Purpose: This study aimed to elucidate the potential mechanism of action of YJPD in the treatment of CRSwNP based on network pharmacology, transcriptomics and experiments.Methods: A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioral tests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation.Results: Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro.Conclusion: YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365509/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S461769","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Yujiang Paidu Decoction (YJPD) has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear.

Purpose: This study aimed to elucidate the potential mechanism of action of YJPD in the treatment of CRSwNP based on network pharmacology, transcriptomics and experiments.

Methods: A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioral tests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation.

Results: Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro.

Conclusion: YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

结合网络药理学和转录组学研究余江白头翁煎剂治疗慢性鼻炎合并鼻息肉的机制

背景：余江派杜煎剂（YJPD）在治疗慢性鼻炎方面具有临床疗效，但其对慢性鼻炎伴鼻息肉（CRSwNP）的作用和机制仍不清楚。目的：本研究旨在基于网络药理学、转录组学和实验，阐明余江派杜煎（YJPD）治疗慢性鼻炎伴鼻息肉（CRSwNP）的潜在作用机制：方法：使用卵清蛋白（OVA）和金黄色葡萄球菌肠毒素B（SEB）建立了为期12周的CRSwNP小鼠模型，并在体外用IL-13诱导了人鼻上皮细胞（HNEpC）模型。通过行为测试、扫描电子显微镜（SEM）、显微 CT 和鼻腔组织病理变化的观察来研究 YJPD 的治疗效果。通过网络药理学和转录组学研究，探讨了YJPD在CRSwNP治疗中的药理机制。最后，进行了ELISA、免疫荧光、RT-qPCR、Western印迹和Tunel验证：结果：不同剂量的YJPD干预能有效缓解CRSwNP小鼠的摩擦和打喷嚏症状。此外，YJPD 还能显著减少异常血清学标志物、鼻黏膜结构损伤、炎性细胞浸润、上睑下垂细胞增生，抑制 OVA 特异性 IgE 水平和 Th2 细胞因子（如 IL-4、IL-5 和 IL-13）的分泌。此外，转录组学和网络药理学分析表明，YJPD 可通过抑制 MAPK/AP-1 信号通路发挥抗炎和抗凋亡作用。实验结果支持了这一结论，在体外 IL13 诱导的 HNEpCs 中观察到的类似结果也进一步证实了这一结论：结论：YJPD 可通过抑制 MAPK/AP-1 信号通路的异常激活来缓解炎症状态和上皮细胞凋亡。这一发现为将 YJPD 用作 CRSwNP 的潜在治疗方法提供了有力依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.