Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation

•GL attenuated inflammatory lung injury.•GL reduced the NETs formation in lung tissues.•GL inhibited the HMGB1 / TLR9 pathway.•GL improved lung function in mice with sepsis-induced ARDS. Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distres...

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Veröffentlicht in:International immunopharmacology 2022-07, Vol.108, p.108730-108730, Article 108730
Hauptverfasser: Gu, Jiarun, Ran, Xufei, Deng, Jin, Zhang, Anqiang, Peng, Guoxuan, Du, Juan, Wen, Dalin, Jiang, Baowei, Xia, Fei
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container_title International immunopharmacology
container_volume 108
creator Gu, Jiarun
Ran, Xufei
Deng, Jin
Zhang, Anqiang
Peng, Guoxuan
Du, Juan
Wen, Dalin
Jiang, Baowei
Xia, Fei
description •GL attenuated inflammatory lung injury.•GL reduced the NETs formation in lung tissues.•GL inhibited the HMGB1 / TLR9 pathway.•GL improved lung function in mice with sepsis-induced ARDS. Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Glycyrrhizin (GL), the main active ingredient of the traditional Chinese medicine Glycyrrhiza glabra, has anti-inflammatory, anti-viral, and immunomodulatory effects. The study aims to explore the efficacy and potential mechanism of GL on sepsis-induced ARDS in mice. Mice were randomly divided into 3 groups: Control, CLP, and GL + CLP. Mice sepsis ARDS model was induced by cecal ligation and puncture (CLP) followed by intraperitoneal GL treatment. Then, the 7-day survival rate of mice was recorded. The lung function of mice was determined by whole-body plethysmography. Lung pathology and scores were observed by hematoxylin-eosin staining. The wet/dry ratio (W/D) of the lung was measured by weighing method. The protein concentration in bronchoalveolar lavage fluid (BALF) was measured by the BCA method. NETs formation in lung tissue was detected by immunofluorescence. Furthermore, HMGB1、TLR9、MyD88 and IL6 expression in lung tissue were detected by western blot and by quantitative real-time PCR, respectively. The results showed that GL improved the survival rate, attenuated lung tissue injury and reduced the expression of inflammatory factors in mice with CLP-induced sepsis. Meanwhile, we confirmed that GL could inhibit TLR9 / MyD88 activation from reducing NETs formation by decreasing HMGB1 expression. The formation of NETs is regulated by HMGB1 / TLR9 / MyD88. In addition, GL improved lung function in mice with sepsis-induced ARDS. Lung function suggested that GL increased alveolar ventilation, alleviated ventilator fatigue and reduced airway resistance in mice with ARDS induced by sepsis. GL ameliorated sepsis-induced ARDS and reduced the NETs formation in lung tissues, which may be associated with the inhibition of the HMGB1 / TLR9 pathway.
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Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Glycyrrhizin (GL), the main active ingredient of the traditional Chinese medicine Glycyrrhiza glabra, has anti-inflammatory, anti-viral, and immunomodulatory effects. The study aims to explore the efficacy and potential mechanism of GL on sepsis-induced ARDS in mice. Mice were randomly divided into 3 groups: Control, CLP, and GL + CLP. Mice sepsis ARDS model was induced by cecal ligation and puncture (CLP) followed by intraperitoneal GL treatment. Then, the 7-day survival rate of mice was recorded. The lung function of mice was determined by whole-body plethysmography. Lung pathology and scores were observed by hematoxylin-eosin staining. The wet/dry ratio (W/D) of the lung was measured by weighing method. The protein concentration in bronchoalveolar lavage fluid (BALF) was measured by the BCA method. NETs formation in lung tissue was detected by immunofluorescence. Furthermore, HMGB1、TLR9、MyD88 and IL6 expression in lung tissue were detected by western blot and by quantitative real-time PCR, respectively. The results showed that GL improved the survival rate, attenuated lung tissue injury and reduced the expression of inflammatory factors in mice with CLP-induced sepsis. Meanwhile, we confirmed that GL could inhibit TLR9 / MyD88 activation from reducing NETs formation by decreasing HMGB1 expression. The formation of NETs is regulated by HMGB1 / TLR9 / MyD88. In addition, GL improved lung function in mice with sepsis-induced ARDS. Lung function suggested that GL increased alveolar ventilation, alleviated ventilator fatigue and reduced airway resistance in mice with ARDS induced by sepsis. 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Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Glycyrrhizin (GL), the main active ingredient of the traditional Chinese medicine Glycyrrhiza glabra, has anti-inflammatory, anti-viral, and immunomodulatory effects. The study aims to explore the efficacy and potential mechanism of GL on sepsis-induced ARDS in mice. Mice were randomly divided into 3 groups: Control, CLP, and GL + CLP. Mice sepsis ARDS model was induced by cecal ligation and puncture (CLP) followed by intraperitoneal GL treatment. Then, the 7-day survival rate of mice was recorded. The lung function of mice was determined by whole-body plethysmography. Lung pathology and scores were observed by hematoxylin-eosin staining. The wet/dry ratio (W/D) of the lung was measured by weighing method. The protein concentration in bronchoalveolar lavage fluid (BALF) was measured by the BCA method. NETs formation in lung tissue was detected by immunofluorescence. Furthermore, HMGB1、TLR9、MyD88 and IL6 expression in lung tissue were detected by western blot and by quantitative real-time PCR, respectively. The results showed that GL improved the survival rate, attenuated lung tissue injury and reduced the expression of inflammatory factors in mice with CLP-induced sepsis. Meanwhile, we confirmed that GL could inhibit TLR9 / MyD88 activation from reducing NETs formation by decreasing HMGB1 expression. The formation of NETs is regulated by HMGB1 / TLR9 / MyD88. In addition, GL improved lung function in mice with sepsis-induced ARDS. Lung function suggested that GL increased alveolar ventilation, alleviated ventilator fatigue and reduced airway resistance in mice with ARDS induced by sepsis. GL ameliorated sepsis-induced ARDS and reduced the NETs formation in lung tissues, which may be associated with the inhibition of the HMGB1 / TLR9 pathway.</description><subject>Acute respiratory distress syndrome</subject><subject>Glycyrrhizin</subject><subject>HMGB1</subject><subject>Neutrophil extracellular traps</subject><subject>Sepsis</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kc9u1DAQxiMEoqXwBgj5yCVb_9nEyQUJKtgiLUJC5WxN7AnrVWIb2ymEl-FV8WoLR04ef_p9M_Z8VfWS0Q2jrL0-bqzLdg4bTjkvUicFfVRdsk52NZO0eVzqppV1I9v-onqW0pHSom_Z0-pCNKLZMsYuq9-7adVrjAf7yzoC04T3FjImkjAkm2rrzKLRENBLRhIxBRsh-7gSY1Mu90KuzkQ_IylOkpYQTqp134gfye2n3Tt2fbf_0pMA-fAD1kTAGeJwydGHg50SwZ85gsZpWiaIpNQhkdHHGbL17nn1ZIQp4YuH86r6-uH93c1tvf-8-3jzdl9r0fJcay5brbXohW604NBJbkwvUQgYwcAgoRUdF_3QG-h0w2EAakY5Dq1EhijFVfX63DdE_33BlNVs0-lR4NAvSfF223RNR1tW0O0Z1dGnFHFUIdoZ4qoYVado1FGdo1GnaNQ5mmJ79TBhGWY0_0x_syjAmzOA5Z_3FqNK2qIr27cRdVbG2_9P-AOKiaei</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Gu, Jiarun</creator><creator>Ran, Xufei</creator><creator>Deng, Jin</creator><creator>Zhang, Anqiang</creator><creator>Peng, Guoxuan</creator><creator>Du, Juan</creator><creator>Wen, Dalin</creator><creator>Jiang, Baowei</creator><creator>Xia, Fei</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20220701</creationdate><title>Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation</title><author>Gu, Jiarun ; Ran, Xufei ; Deng, Jin ; Zhang, Anqiang ; Peng, Guoxuan ; Du, Juan ; Wen, Dalin ; Jiang, Baowei ; Xia, Fei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-c276ccc393c5c32a872dd97e33afadab7a638239b9da8c52aba0df7fb67e1ee73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acute respiratory distress syndrome</topic><topic>Glycyrrhizin</topic><topic>HMGB1</topic><topic>Neutrophil extracellular traps</topic><topic>Sepsis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gu, Jiarun</creatorcontrib><creatorcontrib>Ran, Xufei</creatorcontrib><creatorcontrib>Deng, Jin</creatorcontrib><creatorcontrib>Zhang, Anqiang</creatorcontrib><creatorcontrib>Peng, Guoxuan</creatorcontrib><creatorcontrib>Du, Juan</creatorcontrib><creatorcontrib>Wen, Dalin</creatorcontrib><creatorcontrib>Jiang, Baowei</creatorcontrib><creatorcontrib>Xia, Fei</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gu, Jiarun</au><au>Ran, Xufei</au><au>Deng, Jin</au><au>Zhang, Anqiang</au><au>Peng, Guoxuan</au><au>Du, Juan</au><au>Wen, Dalin</au><au>Jiang, Baowei</au><au>Xia, Fei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>108</volume><spage>108730</spage><epage>108730</epage><pages>108730-108730</pages><artnum>108730</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•GL attenuated inflammatory lung injury.•GL reduced the NETs formation in lung tissues.•GL inhibited the HMGB1 / TLR9 pathway.•GL improved lung function in mice with sepsis-induced ARDS. Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Glycyrrhizin (GL), the main active ingredient of the traditional Chinese medicine Glycyrrhiza glabra, has anti-inflammatory, anti-viral, and immunomodulatory effects. The study aims to explore the efficacy and potential mechanism of GL on sepsis-induced ARDS in mice. Mice were randomly divided into 3 groups: Control, CLP, and GL + CLP. Mice sepsis ARDS model was induced by cecal ligation and puncture (CLP) followed by intraperitoneal GL treatment. Then, the 7-day survival rate of mice was recorded. The lung function of mice was determined by whole-body plethysmography. Lung pathology and scores were observed by hematoxylin-eosin staining. The wet/dry ratio (W/D) of the lung was measured by weighing method. The protein concentration in bronchoalveolar lavage fluid (BALF) was measured by the BCA method. NETs formation in lung tissue was detected by immunofluorescence. Furthermore, HMGB1、TLR9、MyD88 and IL6 expression in lung tissue were detected by western blot and by quantitative real-time PCR, respectively. The results showed that GL improved the survival rate, attenuated lung tissue injury and reduced the expression of inflammatory factors in mice with CLP-induced sepsis. Meanwhile, we confirmed that GL could inhibit TLR9 / MyD88 activation from reducing NETs formation by decreasing HMGB1 expression. The formation of NETs is regulated by HMGB1 / TLR9 / MyD88. In addition, GL improved lung function in mice with sepsis-induced ARDS. Lung function suggested that GL increased alveolar ventilation, alleviated ventilator fatigue and reduced airway resistance in mice with ARDS induced by sepsis. GL ameliorated sepsis-induced ARDS and reduced the NETs formation in lung tissues, which may be associated with the inhibition of the HMGB1 / TLR9 pathway.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>35354111</pmid><doi>10.1016/j.intimp.2022.108730</doi><tpages>1</tpages></addata></record>
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subjects Acute respiratory distress syndrome
Glycyrrhizin
HMGB1
Neutrophil extracellular traps
Sepsis
title Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation
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