Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway
Rosmarinic acid (RA), an ester of caffeic acid and 3, 4‐dihydroxyphenyllactic acid, has anti‐inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug‐likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant‐like potential of RA...
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| Veröffentlicht in: | Phytotherapy research 2021-12, Vol.35 (12), p.6974-6989 |
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| creator | Lataliza, Alexandre Augusto Barros Assis, Pollyana Mendonça Rocha Laurindo, Larissa Gonçalves, Elaine Cristina Dalazen Raposo, Nádia Rezende Barbosa Dutra, Rafael Cypriano |
| description | Rosmarinic acid (RA), an ester of caffeic acid and 3, 4‐dihydroxyphenyllactic acid, has anti‐inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug‐likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant‐like potential of RA in the lipopolysaccharide (LPS)‐induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator‐activated receptor (PPAR) and the cannabinoid receptors CB1 and CB2. In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant‐like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB1, CB2, and PPAR‐γ receptors significantly blocked the antidepressant‐like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR‐γ signaling pathways are involved with the antidepressant‐like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder. |
| doi_str_mv | 10.1002/ptr.7318 |
| format | Article |
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Herein, this study investigated in silico the drug‐likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant‐like potential of RA in the lipopolysaccharide (LPS)‐induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator‐activated receptor (PPAR) and the cannabinoid receptors CB1 and CB2. In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant‐like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB1, CB2, and PPAR‐γ receptors significantly blocked the antidepressant‐like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR‐γ signaling pathways are involved with the antidepressant‐like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.7318</identifier><identifier>PMID: 34709695</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Acids ; Animals ; Antagonists ; Antidepressants ; antidepressant‐like behavior ; Antidepressive Agents - pharmacology ; Bioavailability ; bioinformatics ; Caffeic acid ; cannabimimetic compound ; Cannabinoid CB1 receptors ; Cannabinoid CB2 receptors ; Cinnamates - pharmacology ; Depsides - pharmacology ; Drug therapy ; Grooming ; In vivo methods and tests ; Inflammation ; Lipopolysaccharides ; Mathematical models ; Mental depression ; neuroinflammation ; Neuroinflammatory Diseases - drug therapy ; Neuroprotection ; Parameter identification ; Peroxisome proliferator-activated receptors ; Pharmacokinetics ; Pharmacology ; polyphenol ; PPAR gamma ; Receptors ; Receptors, Cannabinoid ; Rosmarinic Acid ; Signal Transduction ; Signaling</subject><ispartof>Phytotherapy research, 2021-12, Vol.35 (12), p.6974-6989</ispartof><rights>2021 John Wiley & Sons Ltd.</rights><rights>2021 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3498-33488f9d6bb628f5507c397ce564b8d3b8793556ddd1d127bfb9a0fe7afbb5703</citedby><cites>FETCH-LOGICAL-c3498-33488f9d6bb628f5507c397ce564b8d3b8793556ddd1d127bfb9a0fe7afbb5703</cites><orcidid>0000-0002-4710-6799 ; 0000-0001-5271-1048 ; 0000-0003-0682-3019 ; 0000-0002-1905-2527 ; 0000-0002-6938-2161</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%2Fptr.7318$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.7318$$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/34709695$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lataliza, Alexandre Augusto Barros</creatorcontrib><creatorcontrib>Assis, Pollyana Mendonça</creatorcontrib><creatorcontrib>Rocha Laurindo, Larissa</creatorcontrib><creatorcontrib>Gonçalves, Elaine Cristina Dalazen</creatorcontrib><creatorcontrib>Raposo, Nádia Rezende Barbosa</creatorcontrib><creatorcontrib>Dutra, Rafael Cypriano</creatorcontrib><title>Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Rosmarinic acid (RA), an ester of caffeic acid and 3, 4‐dihydroxyphenyllactic acid, has anti‐inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug‐likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant‐like potential of RA in the lipopolysaccharide (LPS)‐induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator‐activated receptor (PPAR) and the cannabinoid receptors CB1 and CB2. In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant‐like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB1, CB2, and PPAR‐γ receptors significantly blocked the antidepressant‐like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR‐γ signaling pathways are involved with the antidepressant‐like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.</description><subject>Acids</subject><subject>Animals</subject><subject>Antagonists</subject><subject>Antidepressants</subject><subject>antidepressant‐like behavior</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Bioavailability</subject><subject>bioinformatics</subject><subject>Caffeic acid</subject><subject>cannabimimetic compound</subject><subject>Cannabinoid CB1 receptors</subject><subject>Cannabinoid CB2 receptors</subject><subject>Cinnamates - pharmacology</subject><subject>Depsides - pharmacology</subject><subject>Drug therapy</subject><subject>Grooming</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Lipopolysaccharides</subject><subject>Mathematical models</subject><subject>Mental depression</subject><subject>neuroinflammation</subject><subject>Neuroinflammatory Diseases - drug therapy</subject><subject>Neuroprotection</subject><subject>Parameter identification</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>polyphenol</subject><subject>PPAR gamma</subject><subject>Receptors</subject><subject>Receptors, Cannabinoid</subject><subject>Rosmarinic Acid</subject><subject>Signal Transduction</subject><subject>Signaling</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV-KFDEQh4Mo7rgKnkACvvjSu0mn00l8Gxb_wYDDOoJvTTqp7GbtTtqkm2XePIKX8ATew0N4EjPuqiD4VBR89VVRP4QeU3JCCalPpzmdCEblHbSiRKmKcsHuohVRnFYNlR-O0IOcrwghqibNfXTEGkFUq_gKfV2H2VuYEuSsw_zj85fBfwQMzoGZcXQ4xTzq5IM3WBtvsV1Kc4E323eF9cEuBiwOsKTogxv0OOo5pj0eo4XhOd5dAp7iDGWJHoprgIPT6BB070MsvgQGpjKST7fb9Xlxfv-Gs78IejismfR8ea33D9E9p4cMj27rMXr_8sXu7HW1efvqzdl6UxnWKFkx1kjplG37vq2l45wIw5QwwNuml5b1UijGeWutpZbWone90sSB0K7vuSDsGD278U4pflogz93os4Fh0AHikruaSyFY3XJZ0Kf_oFdxSeXsQrW0bmqhpPorNOWPOYHrpuTLP_cdJd0huq5E1x2iK-iTW-HSj2D_gL-zKkB1A1z7Afb_FXXb3fkv4U-YIKmj</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Lataliza, Alexandre Augusto Barros</creator><creator>Assis, Pollyana Mendonça</creator><creator>Rocha Laurindo, Larissa</creator><creator>Gonçalves, Elaine Cristina Dalazen</creator><creator>Raposo, Nádia Rezende Barbosa</creator><creator>Dutra, Rafael Cypriano</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4710-6799</orcidid><orcidid>https://orcid.org/0000-0001-5271-1048</orcidid><orcidid>https://orcid.org/0000-0003-0682-3019</orcidid><orcidid>https://orcid.org/0000-0002-1905-2527</orcidid><orcidid>https://orcid.org/0000-0002-6938-2161</orcidid></search><sort><creationdate>202112</creationdate><title>Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway</title><author>Lataliza, Alexandre Augusto Barros ; Assis, Pollyana Mendonça ; Rocha Laurindo, Larissa ; Gonçalves, Elaine Cristina Dalazen ; Raposo, Nádia Rezende Barbosa ; Dutra, Rafael Cypriano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3498-33488f9d6bb628f5507c397ce564b8d3b8793556ddd1d127bfb9a0fe7afbb5703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Antagonists</topic><topic>Antidepressants</topic><topic>antidepressant‐like behavior</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Bioavailability</topic><topic>bioinformatics</topic><topic>Caffeic acid</topic><topic>cannabimimetic compound</topic><topic>Cannabinoid CB1 receptors</topic><topic>Cannabinoid CB2 receptors</topic><topic>Cinnamates - pharmacology</topic><topic>Depsides - pharmacology</topic><topic>Drug therapy</topic><topic>Grooming</topic><topic>In vivo methods and tests</topic><topic>Inflammation</topic><topic>Lipopolysaccharides</topic><topic>Mathematical models</topic><topic>Mental depression</topic><topic>neuroinflammation</topic><topic>Neuroinflammatory Diseases - drug therapy</topic><topic>Neuroprotection</topic><topic>Parameter identification</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>polyphenol</topic><topic>PPAR gamma</topic><topic>Receptors</topic><topic>Receptors, Cannabinoid</topic><topic>Rosmarinic Acid</topic><topic>Signal Transduction</topic><topic>Signaling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lataliza, Alexandre Augusto Barros</creatorcontrib><creatorcontrib>Assis, Pollyana Mendonça</creatorcontrib><creatorcontrib>Rocha Laurindo, Larissa</creatorcontrib><creatorcontrib>Gonçalves, Elaine Cristina Dalazen</creatorcontrib><creatorcontrib>Raposo, Nádia Rezende Barbosa</creatorcontrib><creatorcontrib>Dutra, Rafael Cypriano</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences 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>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lataliza, Alexandre Augusto Barros</au><au>Assis, Pollyana Mendonça</au><au>Rocha Laurindo, Larissa</au><au>Gonçalves, Elaine Cristina Dalazen</au><au>Raposo, Nádia Rezende Barbosa</au><au>Dutra, Rafael Cypriano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2021-12</date><risdate>2021</risdate><volume>35</volume><issue>12</issue><spage>6974</spage><epage>6989</epage><pages>6974-6989</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>Rosmarinic acid (RA), an ester of caffeic acid and 3, 4‐dihydroxyphenyllactic acid, has anti‐inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug‐likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant‐like potential of RA in the lipopolysaccharide (LPS)‐induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator‐activated receptor (PPAR) and the cannabinoid receptors CB1 and CB2. In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant‐like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB1, CB2, and PPAR‐γ receptors significantly blocked the antidepressant‐like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR‐γ signaling pathways are involved with the antidepressant‐like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>34709695</pmid><doi>10.1002/ptr.7318</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-4710-6799</orcidid><orcidid>https://orcid.org/0000-0001-5271-1048</orcidid><orcidid>https://orcid.org/0000-0003-0682-3019</orcidid><orcidid>https://orcid.org/0000-0002-1905-2527</orcidid><orcidid>https://orcid.org/0000-0002-6938-2161</orcidid></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Acids Animals Antagonists Antidepressants antidepressant‐like behavior Antidepressive Agents - pharmacology Bioavailability bioinformatics Caffeic acid cannabimimetic compound Cannabinoid CB1 receptors Cannabinoid CB2 receptors Cinnamates - pharmacology Depsides - pharmacology Drug therapy Grooming In vivo methods and tests Inflammation Lipopolysaccharides Mathematical models Mental depression neuroinflammation Neuroinflammatory Diseases - drug therapy Neuroprotection Parameter identification Peroxisome proliferator-activated receptors Pharmacokinetics Pharmacology polyphenol PPAR gamma Receptors Receptors, Cannabinoid Rosmarinic Acid Signal Transduction Signaling |
| title | Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway |
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