Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein
Background COVID-19, the disease caused by SARS-CoV-2 virus infection, has been a major public health problem worldwide in the last 2 years. SARS-CoV-2-dependent activation of innate immune receptors contributes to the strong local and systemic inflammatory reaction associated with rapid disease evo...
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creator | Segura-Villalobos, Deisy Roa-Velázquez, Daniela Zavala-Vargas, Dan I. Filisola-Villaseñor, Jessica G. Castillo Arellano, Jorge Ivan Morales Ríos, Edgar Reyes-Chilpa, Ricardo González-Espinosa, Claudia |
description | Background
COVID-19, the disease caused by SARS-CoV-2 virus infection, has been a major public health problem worldwide in the last 2 years. SARS-CoV-2-dependent activation of innate immune receptors contributes to the strong local and systemic inflammatory reaction associated with rapid disease evolution. The receptor-binding domain (RBD) of Spike (S) viral protein (S-RBD) is essential for virus infection and its interacting molecules in target cells are still under identification. On the other hand, the search for accessible natural molecules with potential therapeutic use has been intense and remains an active field of investigation.
Methods
C57BL6/J (control) and Toll-like receptor (TLR) 4-deficient (
Lps del
) mice were nebulized with recombinant S-RBD. Tumor Necrosis Factor-alpha (TNF-α) and Interleukin (IL)-6 production in bronchoalveolar lavages (BALs) was determined by enzyme-linked immunosorbent assay (ELISA). Lung-infiltrating cells recovered in BALs were quantified by hematoxylin–eosin (H&E) stain. In selected groups of animals, the natural compound Jacareubin or dexamethasone were intraperitoneally (ip) administered 2 hours before nebulization.
Results
A rapid lung production of TNF-α and IL-6 and cell infiltration was induced by S-RBD nebulization in control but not in
Lps del
mice. Pre-treatment with Jacareubin or dexamethasone prevented S-RBD-induced TNF-α and IL-6 secretion in BALs from control animals.
Conclusions
S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection. |
doi_str_mv | 10.1007/s43440-022-00398-5 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9362068</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2699705042</sourcerecordid><originalsourceid>FETCH-LOGICAL-c376t-759ec102c58b07c93f3119ecac9fe89ba636af0444bd2ad669420538b234af713</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS1ERYfCC7BAXrIxXP8l8QapDP8aqdJMYWs5jjPjktjBTpDm7XGZUsGmK0s-536-8ofQCwqvKUD9JgsuBBBgjABw1RD5CK0YU4rIqhGP0YrWXBBKBZyjpznfAAjKuHyCzrlUHKgSKzR9NdYkt7Q-YB8OvvVzxtebrSA-dIt1HR6WsC9RP5hxNHNMR5xcnmLIDluz5NJoj3g-OLx99x53cTSFFHu8u9zuyDp-JwzvJv_D4SnF2fnwDJ31Zsju-d15gb59_HC9_kw2V5--rC83xPK6mkktlbMUmJVNC7VVvOeUlitjVe8a1ZqKV6YHIUTbMdNVlRIMJG9axoXpa8ov0NsTd1ra0XXWhTmZQU_JjyYddTRe_58Ef9D7-EsrXjGomgJ4dQdI8efi8qxHn60bBhNcXLJmlVI1SBCsVNmpalPMObn-_hkK-laVPqnSRZX-o0rLMvTy3wXvR_66KQV-KuQShb1L-iYuKZRPewj7G60Un7c</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2699705042</pqid></control><display><type>article</type><title>Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Segura-Villalobos, Deisy ; Roa-Velázquez, Daniela ; Zavala-Vargas, Dan I. ; Filisola-Villaseñor, Jessica G. ; Castillo Arellano, Jorge Ivan ; Morales Ríos, Edgar ; Reyes-Chilpa, Ricardo ; González-Espinosa, Claudia</creator><creatorcontrib>Segura-Villalobos, Deisy ; Roa-Velázquez, Daniela ; Zavala-Vargas, Dan I. ; Filisola-Villaseñor, Jessica G. ; Castillo Arellano, Jorge Ivan ; Morales Ríos, Edgar ; Reyes-Chilpa, Ricardo ; González-Espinosa, Claudia</creatorcontrib><description>Background
COVID-19, the disease caused by SARS-CoV-2 virus infection, has been a major public health problem worldwide in the last 2 years. SARS-CoV-2-dependent activation of innate immune receptors contributes to the strong local and systemic inflammatory reaction associated with rapid disease evolution. The receptor-binding domain (RBD) of Spike (S) viral protein (S-RBD) is essential for virus infection and its interacting molecules in target cells are still under identification. On the other hand, the search for accessible natural molecules with potential therapeutic use has been intense and remains an active field of investigation.
Methods
C57BL6/J (control) and Toll-like receptor (TLR) 4-deficient (
Lps del
) mice were nebulized with recombinant S-RBD. Tumor Necrosis Factor-alpha (TNF-α) and Interleukin (IL)-6 production in bronchoalveolar lavages (BALs) was determined by enzyme-linked immunosorbent assay (ELISA). Lung-infiltrating cells recovered in BALs were quantified by hematoxylin–eosin (H&E) stain. In selected groups of animals, the natural compound Jacareubin or dexamethasone were intraperitoneally (ip) administered 2 hours before nebulization.
Results
A rapid lung production of TNF-α and IL-6 and cell infiltration was induced by S-RBD nebulization in control but not in
Lps del
mice. Pre-treatment with Jacareubin or dexamethasone prevented S-RBD-induced TNF-α and IL-6 secretion in BALs from control animals.
Conclusions
S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection.</description><identifier>ISSN: 1734-1140</identifier><identifier>EISSN: 2299-5684</identifier><identifier>DOI: 10.1007/s43440-022-00398-5</identifier><identifier>PMID: 35930194</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Animals ; COVID-19 Drug Treatment ; Dexamethasone ; Drug Safety and Pharmacovigilance ; Inflammation - drug therapy ; Interleukin-6 ; Lung ; Medicine ; Mice ; Pharmacotherapy ; Pharmacy ; SARS-CoV-2 ; Special Issue: Short Communication ; Spike Glycoprotein, Coronavirus ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; Xanthones - pharmacology</subject><ispartof>Pharmacological reports, 2022-12, Vol.74 (6), p.1315-1325</ispartof><rights>The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences 2022</rights><rights>2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-759ec102c58b07c93f3119ecac9fe89ba636af0444bd2ad669420538b234af713</citedby><cites>FETCH-LOGICAL-c376t-759ec102c58b07c93f3119ecac9fe89ba636af0444bd2ad669420538b234af713</cites><orcidid>0000-0001-7332-3829</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s43440-022-00398-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s43440-022-00398-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35930194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Segura-Villalobos, Deisy</creatorcontrib><creatorcontrib>Roa-Velázquez, Daniela</creatorcontrib><creatorcontrib>Zavala-Vargas, Dan I.</creatorcontrib><creatorcontrib>Filisola-Villaseñor, Jessica G.</creatorcontrib><creatorcontrib>Castillo Arellano, Jorge Ivan</creatorcontrib><creatorcontrib>Morales Ríos, Edgar</creatorcontrib><creatorcontrib>Reyes-Chilpa, Ricardo</creatorcontrib><creatorcontrib>González-Espinosa, Claudia</creatorcontrib><title>Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein</title><title>Pharmacological reports</title><addtitle>Pharmacol. Rep</addtitle><addtitle>Pharmacol Rep</addtitle><description>Background
COVID-19, the disease caused by SARS-CoV-2 virus infection, has been a major public health problem worldwide in the last 2 years. SARS-CoV-2-dependent activation of innate immune receptors contributes to the strong local and systemic inflammatory reaction associated with rapid disease evolution. The receptor-binding domain (RBD) of Spike (S) viral protein (S-RBD) is essential for virus infection and its interacting molecules in target cells are still under identification. On the other hand, the search for accessible natural molecules with potential therapeutic use has been intense and remains an active field of investigation.
Methods
C57BL6/J (control) and Toll-like receptor (TLR) 4-deficient (
Lps del
) mice were nebulized with recombinant S-RBD. Tumor Necrosis Factor-alpha (TNF-α) and Interleukin (IL)-6 production in bronchoalveolar lavages (BALs) was determined by enzyme-linked immunosorbent assay (ELISA). Lung-infiltrating cells recovered in BALs were quantified by hematoxylin–eosin (H&E) stain. In selected groups of animals, the natural compound Jacareubin or dexamethasone were intraperitoneally (ip) administered 2 hours before nebulization.
Results
A rapid lung production of TNF-α and IL-6 and cell infiltration was induced by S-RBD nebulization in control but not in
Lps del
mice. Pre-treatment with Jacareubin or dexamethasone prevented S-RBD-induced TNF-α and IL-6 secretion in BALs from control animals.
Conclusions
S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection.</description><subject>Animals</subject><subject>COVID-19 Drug Treatment</subject><subject>Dexamethasone</subject><subject>Drug Safety and Pharmacovigilance</subject><subject>Inflammation - drug therapy</subject><subject>Interleukin-6</subject><subject>Lung</subject><subject>Medicine</subject><subject>Mice</subject><subject>Pharmacotherapy</subject><subject>Pharmacy</subject><subject>SARS-CoV-2</subject><subject>Special Issue: Short Communication</subject><subject>Spike Glycoprotein, Coronavirus</subject><subject>Toll-Like Receptor 4</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Xanthones - pharmacology</subject><issn>1734-1140</issn><issn>2299-5684</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS1ERYfCC7BAXrIxXP8l8QapDP8aqdJMYWs5jjPjktjBTpDm7XGZUsGmK0s-536-8ofQCwqvKUD9JgsuBBBgjABw1RD5CK0YU4rIqhGP0YrWXBBKBZyjpznfAAjKuHyCzrlUHKgSKzR9NdYkt7Q-YB8OvvVzxtebrSA-dIt1HR6WsC9RP5hxNHNMR5xcnmLIDluz5NJoj3g-OLx99x53cTSFFHu8u9zuyDp-JwzvJv_D4SnF2fnwDJ31Zsju-d15gb59_HC9_kw2V5--rC83xPK6mkktlbMUmJVNC7VVvOeUlitjVe8a1ZqKV6YHIUTbMdNVlRIMJG9axoXpa8ov0NsTd1ra0XXWhTmZQU_JjyYddTRe_58Ef9D7-EsrXjGomgJ4dQdI8efi8qxHn60bBhNcXLJmlVI1SBCsVNmpalPMObn-_hkK-laVPqnSRZX-o0rLMvTy3wXvR_66KQV-KuQShb1L-iYuKZRPewj7G60Un7c</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Segura-Villalobos, Deisy</creator><creator>Roa-Velázquez, Daniela</creator><creator>Zavala-Vargas, Dan I.</creator><creator>Filisola-Villaseñor, Jessica G.</creator><creator>Castillo Arellano, Jorge Ivan</creator><creator>Morales Ríos, Edgar</creator><creator>Reyes-Chilpa, Ricardo</creator><creator>González-Espinosa, Claudia</creator><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7332-3829</orcidid></search><sort><creationdate>20221201</creationdate><title>Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein</title><author>Segura-Villalobos, Deisy ; Roa-Velázquez, Daniela ; Zavala-Vargas, Dan I. ; Filisola-Villaseñor, Jessica G. ; Castillo Arellano, Jorge Ivan ; Morales Ríos, Edgar ; Reyes-Chilpa, Ricardo ; González-Espinosa, Claudia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-759ec102c58b07c93f3119ecac9fe89ba636af0444bd2ad669420538b234af713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>COVID-19 Drug Treatment</topic><topic>Dexamethasone</topic><topic>Drug Safety and Pharmacovigilance</topic><topic>Inflammation - drug therapy</topic><topic>Interleukin-6</topic><topic>Lung</topic><topic>Medicine</topic><topic>Mice</topic><topic>Pharmacotherapy</topic><topic>Pharmacy</topic><topic>SARS-CoV-2</topic><topic>Special Issue: Short Communication</topic><topic>Spike Glycoprotein, Coronavirus</topic><topic>Toll-Like Receptor 4</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Xanthones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Segura-Villalobos, Deisy</creatorcontrib><creatorcontrib>Roa-Velázquez, Daniela</creatorcontrib><creatorcontrib>Zavala-Vargas, Dan I.</creatorcontrib><creatorcontrib>Filisola-Villaseñor, Jessica G.</creatorcontrib><creatorcontrib>Castillo Arellano, Jorge Ivan</creatorcontrib><creatorcontrib>Morales Ríos, Edgar</creatorcontrib><creatorcontrib>Reyes-Chilpa, Ricardo</creatorcontrib><creatorcontrib>González-Espinosa, Claudia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pharmacological reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Segura-Villalobos, Deisy</au><au>Roa-Velázquez, Daniela</au><au>Zavala-Vargas, Dan I.</au><au>Filisola-Villaseñor, Jessica G.</au><au>Castillo Arellano, Jorge Ivan</au><au>Morales Ríos, Edgar</au><au>Reyes-Chilpa, Ricardo</au><au>González-Espinosa, Claudia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein</atitle><jtitle>Pharmacological reports</jtitle><stitle>Pharmacol. Rep</stitle><addtitle>Pharmacol Rep</addtitle><date>2022-12-01</date><risdate>2022</risdate><volume>74</volume><issue>6</issue><spage>1315</spage><epage>1325</epage><pages>1315-1325</pages><issn>1734-1140</issn><eissn>2299-5684</eissn><abstract>Background
COVID-19, the disease caused by SARS-CoV-2 virus infection, has been a major public health problem worldwide in the last 2 years. SARS-CoV-2-dependent activation of innate immune receptors contributes to the strong local and systemic inflammatory reaction associated with rapid disease evolution. The receptor-binding domain (RBD) of Spike (S) viral protein (S-RBD) is essential for virus infection and its interacting molecules in target cells are still under identification. On the other hand, the search for accessible natural molecules with potential therapeutic use has been intense and remains an active field of investigation.
Methods
C57BL6/J (control) and Toll-like receptor (TLR) 4-deficient (
Lps del
) mice were nebulized with recombinant S-RBD. Tumor Necrosis Factor-alpha (TNF-α) and Interleukin (IL)-6 production in bronchoalveolar lavages (BALs) was determined by enzyme-linked immunosorbent assay (ELISA). Lung-infiltrating cells recovered in BALs were quantified by hematoxylin–eosin (H&E) stain. In selected groups of animals, the natural compound Jacareubin or dexamethasone were intraperitoneally (ip) administered 2 hours before nebulization.
Results
A rapid lung production of TNF-α and IL-6 and cell infiltration was induced by S-RBD nebulization in control but not in
Lps del
mice. Pre-treatment with Jacareubin or dexamethasone prevented S-RBD-induced TNF-α and IL-6 secretion in BALs from control animals.
Conclusions
S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>35930194</pmid><doi>10.1007/s43440-022-00398-5</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7332-3829</orcidid><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; SpringerNature Journals |
subjects | Animals COVID-19 Drug Treatment Dexamethasone Drug Safety and Pharmacovigilance Inflammation - drug therapy Interleukin-6 Lung Medicine Mice Pharmacotherapy Pharmacy SARS-CoV-2 Special Issue: Short Communication Spike Glycoprotein, Coronavirus Toll-Like Receptor 4 Tumor Necrosis Factor-alpha Xanthones - pharmacology |
title | Jacareubin inhibits TLR4-induced lung inflammatory response caused by the RBD domain of SARS-CoV-2 Spike protein |
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