{"title":"Soshihotang作为缓解长冠肺炎炎症的潜在治疗方案及其相关机制:体外研究和网络药理学分析","authors":"Ga-Ram Yu , Dong-Woo Lim , Won-Hwan Park","doi":"10.1016/j.eujim.2025.102505","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Long COVID is a persistent symptom that appears in many COVID-19 patients, regardless of whether they are asymptomatic, mild, or severe. At least 10 % of the global population suffers from long COVID. The anti-inflammatory effects of six Korean national insurance-covered herbal prescriptions were evaluated in LPS-treated RAW264.7 cells. Additional network pharmacology analysis was conducted to assess their potential for mitigating chronic respiratory tract inflammation. This study aimed to provide an experimental basis for the clinical application of herbal prescriptions and compounds in long COVID patients.</div></div><div><h3>Methods</h3><div>Six candidate prescriptions were selected from the 56 national insurance-covered herbal prescriptions used in Korea. The <em>in vitro</em> efficacies and mechanisms of these six prescriptions on LPS-activated murine macrophages were evaluated. The long COVID-related targets isolated from patients with long COVID and obtained from the GEO online database were identified. These targets were compared with the potential targets of the most potent prescription used in this study.</div></div><div><h3>Results</h3><div>Soshihotang (SST) significantly downregulated iNOS and COX2 expression and reduced the production of nitric oxide and inflammatory cytokines, such as TNFα, IL-1β, and IL-6. SST also inhibited IκBα phosphorylation and reduced the nuclear translocation of NF-κB. Network pharmacological analysis showed that SST influenced the NF-κB signaling pathway. In addition, Saikosaponin D, a major ingredient of Bupleuri Radix (a major herb in SST), showed similar effects and mechanisms to those of SST, including the NF-κB and TNFα signaling pathways. Thus, SST may modulate the inflammatory pathways associated with long COVID through its active component, saikosaponin D.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the potent anti-inflammatory effects of SST are due to its suppression of inflammatory cytokines by blocking NF-κB translocation. In addition, the predicted target was reconfirmed using network pharmacology. Nevertheless, further study on the clinical application of SST as insurance-covered herbal medicine on long COVID patients is needed.</div></div>","PeriodicalId":11932,"journal":{"name":"European Journal of Integrative Medicine","volume":"77 ","pages":"Article 102505"},"PeriodicalIF":1.7000,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Soshihotang as a potential therapeutic option for alleviating inflammation and related mechanisms associated with long COVID: An in vitro study and network pharmacology analysis\",\"authors\":\"Ga-Ram Yu , Dong-Woo Lim , Won-Hwan Park\",\"doi\":\"10.1016/j.eujim.2025.102505\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>Long COVID is a persistent symptom that appears in many COVID-19 patients, regardless of whether they are asymptomatic, mild, or severe. At least 10 % of the global population suffers from long COVID. The anti-inflammatory effects of six Korean national insurance-covered herbal prescriptions were evaluated in LPS-treated RAW264.7 cells. Additional network pharmacology analysis was conducted to assess their potential for mitigating chronic respiratory tract inflammation. This study aimed to provide an experimental basis for the clinical application of herbal prescriptions and compounds in long COVID patients.</div></div><div><h3>Methods</h3><div>Six candidate prescriptions were selected from the 56 national insurance-covered herbal prescriptions used in Korea. The <em>in vitro</em> efficacies and mechanisms of these six prescriptions on LPS-activated murine macrophages were evaluated. The long COVID-related targets isolated from patients with long COVID and obtained from the GEO online database were identified. These targets were compared with the potential targets of the most potent prescription used in this study.</div></div><div><h3>Results</h3><div>Soshihotang (SST) significantly downregulated iNOS and COX2 expression and reduced the production of nitric oxide and inflammatory cytokines, such as TNFα, IL-1β, and IL-6. SST also inhibited IκBα phosphorylation and reduced the nuclear translocation of NF-κB. Network pharmacological analysis showed that SST influenced the NF-κB signaling pathway. In addition, Saikosaponin D, a major ingredient of Bupleuri Radix (a major herb in SST), showed similar effects and mechanisms to those of SST, including the NF-κB and TNFα signaling pathways. Thus, SST may modulate the inflammatory pathways associated with long COVID through its active component, saikosaponin D.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the potent anti-inflammatory effects of SST are due to its suppression of inflammatory cytokines by blocking NF-κB translocation. In addition, the predicted target was reconfirmed using network pharmacology. Nevertheless, further study on the clinical application of SST as insurance-covered herbal medicine on long COVID patients is needed.</div></div>\",\"PeriodicalId\":11932,\"journal\":{\"name\":\"European Journal of Integrative Medicine\",\"volume\":\"77 \",\"pages\":\"Article 102505\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-05-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Integrative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1876382025000575\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Integrative Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1876382025000575","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
long COVID是许多COVID-19患者出现的持续症状,无论他们是无症状、轻度还是重度。全球至少有10%的人口患有长期COVID。在lps处理的RAW264.7细胞中评估6种韩国国民保险中草药的抗炎作用。另外进行了网络药理学分析,以评估其减轻慢性呼吸道炎症的潜力。本研究旨在为中药方剂及复方在长冠肺炎患者中的临床应用提供实验依据。方法从56种全国医保处方中选取6种候选处方。观察6方对lps激活小鼠巨噬细胞的体外作用及机制。从长冠状病毒感染者中分离到的长冠状病毒相关靶点,并从GEO在线数据库中获取。这些靶点与本研究中使用的最有效处方的潜在靶点进行了比较。结果soshihotong (SST)显著下调iNOS和COX2的表达,减少一氧化氮和炎症因子TNFα、IL-1β、IL-6的产生。SST还能抑制i -κB α磷酸化,减少NF-κB的核易位。网络药理学分析表明,SST影响NF-κB信号通路。柴胡中的主要成分柴胡皂苷D (Saikosaponin D)与SST的作用和机制相似,包括NF-κB和tnf - α信号通路。因此,SST可能通过其活性成分柴胡皂苷d调节与长冠肺炎相关的炎症通路。结论这些发现表明,SST的有效抗炎作用可能是通过阻断NF-κB易位来抑制炎症细胞因子。此外,利用网络药理学对预测靶点进行了再确认。然而,SST作为参保中草药在长期COVID患者中的临床应用仍需进一步研究。
Soshihotang as a potential therapeutic option for alleviating inflammation and related mechanisms associated with long COVID: An in vitro study and network pharmacology analysis
Introduction
Long COVID is a persistent symptom that appears in many COVID-19 patients, regardless of whether they are asymptomatic, mild, or severe. At least 10 % of the global population suffers from long COVID. The anti-inflammatory effects of six Korean national insurance-covered herbal prescriptions were evaluated in LPS-treated RAW264.7 cells. Additional network pharmacology analysis was conducted to assess their potential for mitigating chronic respiratory tract inflammation. This study aimed to provide an experimental basis for the clinical application of herbal prescriptions and compounds in long COVID patients.
Methods
Six candidate prescriptions were selected from the 56 national insurance-covered herbal prescriptions used in Korea. The in vitro efficacies and mechanisms of these six prescriptions on LPS-activated murine macrophages were evaluated. The long COVID-related targets isolated from patients with long COVID and obtained from the GEO online database were identified. These targets were compared with the potential targets of the most potent prescription used in this study.
Results
Soshihotang (SST) significantly downregulated iNOS and COX2 expression and reduced the production of nitric oxide and inflammatory cytokines, such as TNFα, IL-1β, and IL-6. SST also inhibited IκBα phosphorylation and reduced the nuclear translocation of NF-κB. Network pharmacological analysis showed that SST influenced the NF-κB signaling pathway. In addition, Saikosaponin D, a major ingredient of Bupleuri Radix (a major herb in SST), showed similar effects and mechanisms to those of SST, including the NF-κB and TNFα signaling pathways. Thus, SST may modulate the inflammatory pathways associated with long COVID through its active component, saikosaponin D.
Conclusion
These findings suggest that the potent anti-inflammatory effects of SST are due to its suppression of inflammatory cytokines by blocking NF-κB translocation. In addition, the predicted target was reconfirmed using network pharmacology. Nevertheless, further study on the clinical application of SST as insurance-covered herbal medicine on long COVID patients is needed.
期刊介绍:
The European Journal of Integrative Medicine (EuJIM) considers manuscripts from a wide range of complementary and integrative health care disciplines, with a particular focus on whole systems approaches, public health, self management and traditional medical systems. The journal strives to connect conventional medicine and evidence based complementary medicine. We encourage submissions reporting research with relevance for integrative clinical practice and interprofessional education.
EuJIM aims to be of interest to both conventional and integrative audiences, including healthcare practitioners, researchers, health care organisations, educationalists, and all those who seek objective and critical information on integrative medicine. To achieve this aim EuJIM provides an innovative international and interdisciplinary platform linking researchers and clinicians.
The journal focuses primarily on original research articles including systematic reviews, randomized controlled trials, other clinical studies, qualitative, observational and epidemiological studies. In addition we welcome short reviews, opinion articles and contributions relating to health services and policy, health economics and psychology.