Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses
Osthole (also known as Osthol) is the main anti‐inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality‐controlled component according the Chinese Pharmacopoeia. However, its underlying anti‐inflammatory mechanism remains unknown. In this study, we demonstrated that Ostho...
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| Veröffentlicht in: | Chemistry & biodiversity 2024-04, Vol.21 (4), p.e202400290-n/a |
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| creator | Li, Shu‐Hang Li, Meng‐Ying Yuan, Tao‐Tao Wang, Guo‐Wei Zeng, Jian‐Bin Shi, Zhimian Liu, Jian‐Hang Su, Jun‐Cheng |
| description | Osthole (also known as Osthol) is the main anti‐inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality‐controlled component according the Chinese Pharmacopoeia. However, its underlying anti‐inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF‐α, but not IL‐6 in the classical LPS‐stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF‐κB signalling pathways, of which the former was dose‐dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose‐dependently up‐regulated the expression of the key cholinergic anti‐inflammatory pathway regulator α7nAChR, and the TNF‐α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF‐α by promoting the expression of α7nAChR, thereby activate the vagus nerve‐dependent cholinergic anti‐inflammatory pathway. |
| doi_str_mv | 10.1002/cbdv.202400290 |
| format | Article |
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However, its underlying anti‐inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF‐α, but not IL‐6 in the classical LPS‐stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF‐κB signalling pathways, of which the former was dose‐dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose‐dependently up‐regulated the expression of the key cholinergic anti‐inflammatory pathway regulator α7nAChR, and the TNF‐α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF‐α by promoting the expression of α7nAChR, thereby activate the vagus nerve‐dependent cholinergic anti‐inflammatory pathway.</description><identifier>ISSN: 1612-1872</identifier><identifier>EISSN: 1612-1880</identifier><identifier>DOI: 10.1002/cbdv.202400290</identifier><identifier>PMID: 38389159</identifier><language>eng</language><publisher>Switzerland: Wiley Subscription Services, Inc</publisher><subject>acetylcholine ; anti-inflammatory activity ; cholinergic anti-inflammatory pathway ; Cholinergics ; Coumarin ; Inflammation ; Lipopolysaccharides ; Macrophages ; MAP kinase ; Osthole ; Phosphorylation ; Proteins ; Signal transduction ; Vagus nerve</subject><ispartof>Chemistry & biodiversity, 2024-04, Vol.21 (4), p.e202400290-n/a</ispartof><rights>2024 Wiley‐VHCA AG, Zurich, Switzerland</rights><rights>2024 Wiley-VHCA AG, Zurich, Switzerland.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3280-4e0cb55aad7e0779520a9ede9264d29d8a835b8e2448766d2a7d196b6ac4df1c3</cites><orcidid>0000-0002-1458-5383</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbdv.202400290$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbdv.202400290$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38389159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Shu‐Hang</creatorcontrib><creatorcontrib>Li, Meng‐Ying</creatorcontrib><creatorcontrib>Yuan, Tao‐Tao</creatorcontrib><creatorcontrib>Wang, Guo‐Wei</creatorcontrib><creatorcontrib>Zeng, Jian‐Bin</creatorcontrib><creatorcontrib>Shi, Zhimian</creatorcontrib><creatorcontrib>Liu, Jian‐Hang</creatorcontrib><creatorcontrib>Su, Jun‐Cheng</creatorcontrib><title>Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses</title><title>Chemistry & biodiversity</title><addtitle>Chem Biodivers</addtitle><description>Osthole (also known as Osthol) is the main anti‐inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality‐controlled component according the Chinese Pharmacopoeia. However, its underlying anti‐inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF‐α, but not IL‐6 in the classical LPS‐stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF‐κB signalling pathways, of which the former was dose‐dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose‐dependently up‐regulated the expression of the key cholinergic anti‐inflammatory pathway regulator α7nAChR, and the TNF‐α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF‐α by promoting the expression of α7nAChR, thereby activate the vagus nerve‐dependent cholinergic anti‐inflammatory pathway.</description><subject>acetylcholine</subject><subject>anti-inflammatory activity</subject><subject>cholinergic anti-inflammatory pathway</subject><subject>Cholinergics</subject><subject>Coumarin</subject><subject>Inflammation</subject><subject>Lipopolysaccharides</subject><subject>Macrophages</subject><subject>MAP kinase</subject><subject>Osthole</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Vagus nerve</subject><issn>1612-1872</issn><issn>1612-1880</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqF0c1uVCEYBmDSaNpau-3SkLhxMyNw_mB5evxr0qRNY90SDnzToeEcpsCZZuLGS_BWvBEvwiuRZuoYu3EFfHm-NyQvQieUzCkh7K3uzXrOCCvzQ5A9dEhrymaUc_Jsd2_YAXoR420mec730UHBCy5oJQ7R14uYlt4BbnWya5Ug4rQE3OWZHSHcWI3bMdlf376fjQunhkElHzb4UqXlvdrgtVX4549mbLvlFb5eBbiZnErWjzh53DoHGSTA_-xeQVz5MUJ8iZ4vlItw_HgeoesP7z93n2bnFx_PuvZ8pgvGyawEovuqUso0QJpGVIwoAQYEq0vDhOGKF1XPgZUlb-raMNUYKuq-Vro0C6qLI_Rmm7sK_m6CmORgowbn1Ah-ipKJklEueMUyff2E3vopjPl3siCFqBtRVDSr-Vbp4GMMsJCrYAcVNpIS-VCLfKhF7mrJC68eY6d-ALPjf3rIQGzBvXWw-U-c7E7fffkb_hv49Jxa</recordid><startdate>202404</startdate><enddate>202404</enddate><creator>Li, Shu‐Hang</creator><creator>Li, Meng‐Ying</creator><creator>Yuan, Tao‐Tao</creator><creator>Wang, Guo‐Wei</creator><creator>Zeng, Jian‐Bin</creator><creator>Shi, Zhimian</creator><creator>Liu, Jian‐Hang</creator><creator>Su, Jun‐Cheng</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1458-5383</orcidid></search><sort><creationdate>202404</creationdate><title>Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses</title><author>Li, Shu‐Hang ; Li, Meng‐Ying ; Yuan, Tao‐Tao ; Wang, Guo‐Wei ; Zeng, Jian‐Bin ; Shi, Zhimian ; Liu, Jian‐Hang ; Su, Jun‐Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3280-4e0cb55aad7e0779520a9ede9264d29d8a835b8e2448766d2a7d196b6ac4df1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>acetylcholine</topic><topic>anti-inflammatory activity</topic><topic>cholinergic anti-inflammatory pathway</topic><topic>Cholinergics</topic><topic>Coumarin</topic><topic>Inflammation</topic><topic>Lipopolysaccharides</topic><topic>Macrophages</topic><topic>MAP kinase</topic><topic>Osthole</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Vagus nerve</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Shu‐Hang</creatorcontrib><creatorcontrib>Li, Meng‐Ying</creatorcontrib><creatorcontrib>Yuan, Tao‐Tao</creatorcontrib><creatorcontrib>Wang, Guo‐Wei</creatorcontrib><creatorcontrib>Zeng, Jian‐Bin</creatorcontrib><creatorcontrib>Shi, Zhimian</creatorcontrib><creatorcontrib>Liu, Jian‐Hang</creatorcontrib><creatorcontrib>Su, Jun‐Cheng</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry & biodiversity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Shu‐Hang</au><au>Li, Meng‐Ying</au><au>Yuan, Tao‐Tao</au><au>Wang, Guo‐Wei</au><au>Zeng, Jian‐Bin</au><au>Shi, Zhimian</au><au>Liu, Jian‐Hang</au><au>Su, Jun‐Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses</atitle><jtitle>Chemistry & biodiversity</jtitle><addtitle>Chem Biodivers</addtitle><date>2024-04</date><risdate>2024</risdate><volume>21</volume><issue>4</issue><spage>e202400290</spage><epage>n/a</epage><pages>e202400290-n/a</pages><issn>1612-1872</issn><eissn>1612-1880</eissn><abstract>Osthole (also known as Osthol) is the main anti‐inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality‐controlled component according the Chinese Pharmacopoeia. However, its underlying anti‐inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF‐α, but not IL‐6 in the classical LPS‐stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF‐κB signalling pathways, of which the former was dose‐dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose‐dependently up‐regulated the expression of the key cholinergic anti‐inflammatory pathway regulator α7nAChR, and the TNF‐α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF‐α by promoting the expression of α7nAChR, thereby activate the vagus nerve‐dependent cholinergic anti‐inflammatory pathway.</abstract><cop>Switzerland</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38389159</pmid><doi>10.1002/cbdv.202400290</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-1458-5383</orcidid></addata></record> |
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| subjects | acetylcholine anti-inflammatory activity cholinergic anti-inflammatory pathway Cholinergics Coumarin Inflammation Lipopolysaccharides Macrophages MAP kinase Osthole Phosphorylation Proteins Signal transduction Vagus nerve |
| title | Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses |
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