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Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19.
Zhao, Jing; Tian, Saisai; Lu, Dong; Yang, Jian; Zeng, Huawu; Zhang, Feng; Tu, Dongzhu; Ge, Guangbo; Zheng, Yuejuan; Shi, Ting; Xu, Xin; Zhao, Shiyi; Yang, Yili; Zhang, Weidong.
  • Zhao J; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Tian S; School of Pharmacy, Second Military Medical University, Shanghai, China.
  • Lu D; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Yang J; School of Pharmacy, Second Military Medical University, Shanghai, China.
  • Zeng H; School of Pharmacy, Second Military Medical University, Shanghai, China.
  • Zhang F; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Tu D; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Ge G; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Zheng Y; Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Shi T; Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Xu X; Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
  • Zhao S; Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
  • Yang Y; Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
  • Zhang W; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; School of Pharmacy, Second Military Medical University, Shanghai, China. Electronic address: wdzhangy@hotmail.com.
Phytomedicine ; 85: 153315, 2021 May.
Article in English | MEDLINE | ID: covidwho-752997
Semantic information from SemMedBD (by NLM)
1. Organ LOCATION_OF Protection
Subject
Organ
Predicate
LOCATION_OF
Object
Protection
2. Anti-Inflammatory Agents AFFECTS Immune
Subject
Anti-Inflammatory Agents
Predicate
AFFECTS
Object
Immune
3. Severe Acute Respiratory Syndrome AFFECTS High Confidence
Subject
Severe Acute Respiratory Syndrome
Predicate
AFFECTS
Object
High Confidence
4. 2019 novel coronavirus INTERACTS_WITH Virus
Subject
2019 novel coronavirus
Predicate
INTERACTS_WITH
Object
Virus
5. Transcriptional Activation AFFECTS interleukin-10|IL10
Subject
Transcriptional Activation
Predicate
AFFECTS
Object
interleukin-10|IL10
6. Organ LOCATION_OF Protection
Subject
Organ
Predicate
LOCATION_OF
Object
Protection
7. Anti-Inflammatory Agents AFFECTS Immune
Subject
Anti-Inflammatory Agents
Predicate
AFFECTS
Object
Immune
8. Severe Acute Respiratory Syndrome AFFECTS High Confidence
Subject
Severe Acute Respiratory Syndrome
Predicate
AFFECTS
Object
High Confidence
9. 2019 novel coronavirus INTERACTS_WITH Virus
Subject
2019 novel coronavirus
Predicate
INTERACTS_WITH
Object
Virus
10. Transcriptional Activation AFFECTS interleukin-10|IL10
Subject
Transcriptional Activation
Predicate
AFFECTS
Object
interleukin-10|IL10
ABSTRACT

BACKGROUND:

The traditional Chinese medicine (TCM) formula Qing-Fei-Pai-Du decoction (QFPDD) was the most widely used prescription in China's campaign to contain COVID-19, which has exhibited positive effects. However, the underlying mode of action is largely unknown.

PURPOSE:

A systems pharmacology strategy was proposed to investigate the mechanisms of QFPDD against COVID-19 from molecule, pathway and network levels. STUDY DESIGN AND

METHODS:

The systems pharmacological approach consisted of text mining, target prediction, data integration, network study, bioinformatics analysis, molecular docking, and pharmacological validation. Especially, we proposed a scoring method to measure the confidence of targets identified by prediction and text mining, while a novel scheme was used to identify important targets from 4 aspects.

RESULTS:

623 high-confidence targets of QFPDD's 12 active compounds were identified, 88 of which were overlapped with genes affected by SARS-CoV-2 infection. These targets were found to be involved in biological processes related with the development of COVID-19, such as pattern recognition receptor signaling, interleukin signaling, cell growth and death, hemostasis, and injuries of the nervous, sensory, circulatory, and digestive systems. Comprehensive network and pathway analysis were used to identify 55 important targets, which regulated 5 functional modules corresponding to QFPDD's effects in immune regulation, anti-infection, anti-inflammation, and multi-organ protection, respectively. Four compounds (baicalin, glycyrrhizic acid, hesperidin, and hyperoside) and 7 targets (AKT1, TNF-α, IL6, PTGS2, HMOX1, IL10, and TP53) were key molecules related to QFPDD's effects. Molecular docking verified that QFPDD's compounds may bind to 6 host proteins that interact with SARS-CoV-2 proteins, further supported the anti-virus effect of QFPDD. At last, in intro experiments validated QFPDD's important effects, including the inhibition of IL6, CCL2, TNF-α, NF-κB, PTGS1/2, CYP1A1, CYP3A4 activity, the up-regulation of IL10 expression, and repressing platelet aggregation.

CONCLUSION:

This work illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation, and multi-organ protection. It may strengthen the understanding of QFPDD and facilitate more application of this formula in the campaign to SARS-CoV-2.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Drugs, Chinese Herbal / SARS-CoV-2 Type of study: Diagnostic study / Prognostic study Topics: Traditional medicine Limits: Animals / Humans / Male Language: English Journal: Phytomedicine Journal subject: Complementary Therapies Year: 2021 Document Type: Article Affiliation country: J.phymed.2020.153315

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Drugs, Chinese Herbal / SARS-CoV-2 Type of study: Diagnostic study / Prognostic study Topics: Traditional medicine Limits: Animals / Humans / Male Language: English Journal: Phytomedicine Journal subject: Complementary Therapies Year: 2021 Document Type: Article Affiliation country: J.phymed.2020.153315