Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway

•Yindan Jiedu Granules (YDJDG) is a new Chinese herbal formula for COVID-19.•YDJDG could shorten the course and delay the progression of COVID-19.•We provide clinical, bioinformatics and experiment basis for COVID-19 treatment with YDJDG.•YDJDG may suppressing inflammation via targeting the NF-κB pa...

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Veröffentlicht in:Phytomedicine (Stuttgart) 2022-01, Vol.95, p.153784-153784, Article 153784
Hauptverfasser: Feng, Ying, Zhu, Bingbing, Liu, Yao, Zhou, Guiqin, Yang, Li, Liu, Long, Ren, Jie, Hou, Yixin, Yu, Hao, Meng, Peipei, Jiang, Yuyong, Wang, Xianbo
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container_title Phytomedicine (Stuttgart)
container_volume 95
creator Feng, Ying
Zhu, Bingbing
Liu, Yao
Liu, Yao
Zhou, Guiqin
Yang, Li
Liu, Long
Ren, Jie
Hou, Yixin
Yu, Hao
Meng, Peipei
Jiang, Yuyong
Wang, Xianbo
description •Yindan Jiedu Granules (YDJDG) is a new Chinese herbal formula for COVID-19.•YDJDG could shorten the course and delay the progression of COVID-19.•We provide clinical, bioinformatics and experiment basis for COVID-19 treatment with YDJDG.•YDJDG may suppressing inflammation via targeting the NF-κB pathway. Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of infl
doi_str_mv 10.1016/j.phymed.2021.153784
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Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p &lt; 0.0001), shorter time to negative conversion of viral nucleic acid (p &lt; 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p &lt; 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1β, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway. [Display omitted]</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2021.153784</identifier><identifier>PMID: 34785108</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Clinical research ; COVID-19 ; Cytokines ; Humans ; Lipopolysaccharides - pharmacology ; Molecular docking ; Molecular Docking Simulation ; NF-kappa B - metabolism ; NF-κB signaling pathway ; Pharmacology analysis ; SARS-CoV-2 ; Signal Transduction ; Tandem Mass Spectrometry ; Yindan jiedugranules</subject><ispartof>Phytomedicine (Stuttgart), 2022-01, Vol.95, p.153784-153784, Article 153784</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier GmbH.</rights><rights>2021 The Authors. Published by Elsevier GmbH. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-72ff81c1baeb2c3a2af0fd7f39807a94fefc8bf5e6a7861837e06632078ef06e3</citedby><cites>FETCH-LOGICAL-c463t-72ff81c1baeb2c3a2af0fd7f39807a94fefc8bf5e6a7861837e06632078ef06e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.phymed.2021.153784$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34785108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Ying</creatorcontrib><creatorcontrib>Zhu, Bingbing</creatorcontrib><creatorcontrib>Liu, Yao</creatorcontrib><creatorcontrib>Liu, Yao</creatorcontrib><creatorcontrib>Zhou, Guiqin</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Liu, Long</creatorcontrib><creatorcontrib>Ren, Jie</creatorcontrib><creatorcontrib>Hou, Yixin</creatorcontrib><creatorcontrib>Yu, Hao</creatorcontrib><creatorcontrib>Meng, Peipei</creatorcontrib><creatorcontrib>Jiang, Yuyong</creatorcontrib><creatorcontrib>Wang, Xianbo</creatorcontrib><title>Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>•Yindan Jiedu Granules (YDJDG) is a new Chinese herbal formula for COVID-19.•YDJDG could shorten the course and delay the progression of COVID-19.•We provide clinical, bioinformatics and experiment basis for COVID-19 treatment with YDJDG.•YDJDG may suppressing inflammation via targeting the NF-κB pathway. Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p &lt; 0.0001), shorter time to negative conversion of viral nucleic acid (p &lt; 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p &lt; 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1β, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway. [Display omitted]</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Clinical research</subject><subject>COVID-19</subject><subject>Cytokines</subject><subject>Humans</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB signaling pathway</subject><subject>Pharmacology analysis</subject><subject>SARS-CoV-2</subject><subject>Signal Transduction</subject><subject>Tandem Mass Spectrometry</subject><subject>Yindan jiedugranules</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuO1DAQhi0EYpqBGyDk5bBIY-dlZ4MEDQODRswGEKwsxyl33ErsYDs95CachUNwJtzqYYANq5Lq8VfV_yH0mJI1JbR-tltP_TJCt85JTte0Khgv76AVrSnPSFN9votWpCnLjFFanKAHIewIoWXDyH10UpSMV5TwFfr-xdhOWvzOQDfjrZd2HiBg-Nab1kQsbTSZsXqQ4yij8wsGrUFFbCyeZDRgY8DXJvbYuj0MeOO8s3Jv_BxwZwLIAPhsc_Xp4lVGm6e4XXCYp8lDCMZucewBvz_Pfv54iYPZWjkckkm2v5bLQ3RPyyHAo5t4ij6ev_6weZtdXr252Ly4zFRZFzFjudacKtpKaHNVyFxqojumi4YTJptSg1a81RXUkvFkTcGA1HWRE8ZBkxqKU_T8qDvNbXJTpY-8HMTkzSj9Ipw04t-KNb3Yur3gJS8pp0ng7EbAu68zhChGExQMg7Tg5iDyquEJTsHy1FoeW5V3IXjQt2soEQeoYieOUMUBqjhCTWNP_j7xdug3xT8_QDJqb8CLoBIaBZ3xCZbonPn_hl-usLnh</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Feng, Ying</creator><creator>Zhu, Bingbing</creator><creator>Liu, Yao</creator><creator>Liu, Yao</creator><creator>Zhou, Guiqin</creator><creator>Yang, Li</creator><creator>Liu, Long</creator><creator>Ren, Jie</creator><creator>Hou, Yixin</creator><creator>Yu, Hao</creator><creator>Meng, Peipei</creator><creator>Jiang, Yuyong</creator><creator>Wang, Xianbo</creator><general>Elsevier GmbH</general><general>The Authors. 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Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p &lt; 0.0001), shorter time to negative conversion of viral nucleic acid (p &lt; 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p &lt; 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1β, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway. [Display omitted]</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>34785108</pmid><doi>10.1016/j.phymed.2021.153784</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Anti-Inflammatory Agents - pharmacology
Clinical research
COVID-19
Cytokines
Humans
Lipopolysaccharides - pharmacology
Molecular docking
Molecular Docking Simulation
NF-kappa B - metabolism
NF-κB signaling pathway
Pharmacology analysis
SARS-CoV-2
Signal Transduction
Tandem Mass Spectrometry
Yindan jiedugranules
title Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway
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