γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block
Abstract Objectives Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on canc...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2022-11, Vol.74 (11), p.1629-1639 |
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| creator | Pina, Lícia T S Rabelo, Thallita K Trindade, Gabriela G G Almeida, Iggo K S Oliveira, Marlange A dos Santos, Priscila L Souza, Diego Santos de Menezes-Filho, José E R de Vasconcelos, Carla Maria Lins Santos, Sandra L Scotti, Luciana Scotti, Marcus T Araújo, Adriano A S Quintans, Jullyana S S Quintans, Lucindo J Guimarães, Adriana G |
| description | Abstract
Objectives
Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.
Methods
The γ-TPN/β-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, γ-TPN 50 mg/kg, γ-TPN/β-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-α and IL-1β levels, iNOS and c-Fos activity. The effects of γ-TPN on calcium channels were studied by patch-clamp and molecular docking.
Results
β-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1β, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.
Conclusion
These results indicate that the complexation of γ-TPN into β-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels. |
| doi_str_mv | 10.1093/jpp/rgac052 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2703416065</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/jpp/rgac052</oup_id><sourcerecordid>2703416065</sourcerecordid><originalsourceid>FETCH-LOGICAL-c227t-7275076060d89a30c088fcf81f28c97ae1ed7cf91dc7cfa1f87f0f5afdee6e6a3</originalsourceid><addsrcrecordid>eNp9kE1OwzAQhS0EEqWw4gJeIaQqYDtNnCxRxZ9UiU1ZR-5kTFNSJ9gONAsuBffomXCVrlm9xXxvZt4j5JKzG87y-Hbdtrf2TQFLxBEZCTYVkeRJdkxGjAkRxYmMT8mZc2vGmEzTdES-d7_RAm1bGTRIodm0NW6xpF-VX9HdTwQ91E2JW28rQ5X3aDrl0VEXHKqmBjvbKPDVZ-V7ukdMtVG1G_ygDKClrQqDZU9nSkworJQxWNNl3cD7OTnRgcaLg47J68P9YvYUzV8en2d38wiEkD6SQibhX5ayMstVzIBlmQadcS0yyKVCjqUEnfMSgiiuM6mZTpQuEVNMVTwm18Pe1jYfHTpfbCoHWNfKYNO5QkgWT3k4kAR0MqBgG-cs6qK1IZLtC86KfclFKLk4lBzoq4FuuvZf8A_H6YKc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2703416065</pqid></control><display><type>article</type><title>γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block</title><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Pina, Lícia T S ; Rabelo, Thallita K ; Trindade, Gabriela G G ; Almeida, Iggo K S ; Oliveira, Marlange A ; dos Santos, Priscila L ; Souza, Diego Santos ; de Menezes-Filho, José E R ; de Vasconcelos, Carla Maria Lins ; Santos, Sandra L ; Scotti, Luciana ; Scotti, Marcus T ; Araújo, Adriano A S ; Quintans, Jullyana S S ; Quintans, Lucindo J ; Guimarães, Adriana G</creator><creatorcontrib>Pina, Lícia T S ; Rabelo, Thallita K ; Trindade, Gabriela G G ; Almeida, Iggo K S ; Oliveira, Marlange A ; dos Santos, Priscila L ; Souza, Diego Santos ; de Menezes-Filho, José E R ; de Vasconcelos, Carla Maria Lins ; Santos, Sandra L ; Scotti, Luciana ; Scotti, Marcus T ; Araújo, Adriano A S ; Quintans, Jullyana S S ; Quintans, Lucindo J ; Guimarães, Adriana G</creatorcontrib><description>Abstract
Objectives
Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.
Methods
The γ-TPN/β-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, γ-TPN 50 mg/kg, γ-TPN/β-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-α and IL-1β levels, iNOS and c-Fos activity. The effects of γ-TPN on calcium channels were studied by patch-clamp and molecular docking.
Results
β-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1β, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.
Conclusion
These results indicate that the complexation of γ-TPN into β-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1093/jpp/rgac052</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><ispartof>Journal of pharmacy and pharmacology, 2022-11, Vol.74 (11), p.1629-1639</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c227t-7275076060d89a30c088fcf81f28c97ae1ed7cf91dc7cfa1f87f0f5afdee6e6a3</citedby><cites>FETCH-LOGICAL-c227t-7275076060d89a30c088fcf81f28c97ae1ed7cf91dc7cfa1f87f0f5afdee6e6a3</cites><orcidid>0000-0003-1643-5642 ; 0000-0002-7197-0261</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids></links><search><creatorcontrib>Pina, Lícia T S</creatorcontrib><creatorcontrib>Rabelo, Thallita K</creatorcontrib><creatorcontrib>Trindade, Gabriela G G</creatorcontrib><creatorcontrib>Almeida, Iggo K S</creatorcontrib><creatorcontrib>Oliveira, Marlange A</creatorcontrib><creatorcontrib>dos Santos, Priscila L</creatorcontrib><creatorcontrib>Souza, Diego Santos</creatorcontrib><creatorcontrib>de Menezes-Filho, José E R</creatorcontrib><creatorcontrib>de Vasconcelos, Carla Maria Lins</creatorcontrib><creatorcontrib>Santos, Sandra L</creatorcontrib><creatorcontrib>Scotti, Luciana</creatorcontrib><creatorcontrib>Scotti, Marcus T</creatorcontrib><creatorcontrib>Araújo, Adriano A S</creatorcontrib><creatorcontrib>Quintans, Jullyana S S</creatorcontrib><creatorcontrib>Quintans, Lucindo J</creatorcontrib><creatorcontrib>Guimarães, Adriana G</creatorcontrib><title>γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block</title><title>Journal of pharmacy and pharmacology</title><description>Abstract
Objectives
Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.
Methods
The γ-TPN/β-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, γ-TPN 50 mg/kg, γ-TPN/β-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-α and IL-1β levels, iNOS and c-Fos activity. The effects of γ-TPN on calcium channels were studied by patch-clamp and molecular docking.
Results
β-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1β, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.
Conclusion
These results indicate that the complexation of γ-TPN into β-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels.</description><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kE1OwzAQhS0EEqWw4gJeIaQqYDtNnCxRxZ9UiU1ZR-5kTFNSJ9gONAsuBffomXCVrlm9xXxvZt4j5JKzG87y-Hbdtrf2TQFLxBEZCTYVkeRJdkxGjAkRxYmMT8mZc2vGmEzTdES-d7_RAm1bGTRIodm0NW6xpF-VX9HdTwQ91E2JW28rQ5X3aDrl0VEXHKqmBjvbKPDVZ-V7ukdMtVG1G_ygDKClrQqDZU9nSkworJQxWNNl3cD7OTnRgcaLg47J68P9YvYUzV8en2d38wiEkD6SQibhX5ayMstVzIBlmQadcS0yyKVCjqUEnfMSgiiuM6mZTpQuEVNMVTwm18Pe1jYfHTpfbCoHWNfKYNO5QkgWT3k4kAR0MqBgG-cs6qK1IZLtC86KfclFKLk4lBzoq4FuuvZf8A_H6YKc</recordid><startdate>20221104</startdate><enddate>20221104</enddate><creator>Pina, Lícia T S</creator><creator>Rabelo, Thallita K</creator><creator>Trindade, Gabriela G G</creator><creator>Almeida, Iggo K S</creator><creator>Oliveira, Marlange A</creator><creator>dos Santos, Priscila L</creator><creator>Souza, Diego Santos</creator><creator>de Menezes-Filho, José E R</creator><creator>de Vasconcelos, Carla Maria Lins</creator><creator>Santos, Sandra L</creator><creator>Scotti, Luciana</creator><creator>Scotti, Marcus T</creator><creator>Araújo, Adriano A S</creator><creator>Quintans, Jullyana S S</creator><creator>Quintans, Lucindo J</creator><creator>Guimarães, Adriana G</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1643-5642</orcidid><orcidid>https://orcid.org/0000-0002-7197-0261</orcidid></search><sort><creationdate>20221104</creationdate><title>γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block</title><author>Pina, Lícia T S ; Rabelo, Thallita K ; Trindade, Gabriela G G ; Almeida, Iggo K S ; Oliveira, Marlange A ; dos Santos, Priscila L ; Souza, Diego Santos ; de Menezes-Filho, José E R ; de Vasconcelos, Carla Maria Lins ; Santos, Sandra L ; Scotti, Luciana ; Scotti, Marcus T ; Araújo, Adriano A S ; Quintans, Jullyana S S ; Quintans, Lucindo J ; Guimarães, Adriana G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c227t-7275076060d89a30c088fcf81f28c97ae1ed7cf91dc7cfa1f87f0f5afdee6e6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pina, Lícia T S</creatorcontrib><creatorcontrib>Rabelo, Thallita K</creatorcontrib><creatorcontrib>Trindade, Gabriela G G</creatorcontrib><creatorcontrib>Almeida, Iggo K S</creatorcontrib><creatorcontrib>Oliveira, Marlange A</creatorcontrib><creatorcontrib>dos Santos, Priscila L</creatorcontrib><creatorcontrib>Souza, Diego Santos</creatorcontrib><creatorcontrib>de Menezes-Filho, José E R</creatorcontrib><creatorcontrib>de Vasconcelos, Carla Maria Lins</creatorcontrib><creatorcontrib>Santos, Sandra L</creatorcontrib><creatorcontrib>Scotti, Luciana</creatorcontrib><creatorcontrib>Scotti, Marcus T</creatorcontrib><creatorcontrib>Araújo, Adriano A S</creatorcontrib><creatorcontrib>Quintans, Jullyana S S</creatorcontrib><creatorcontrib>Quintans, Lucindo J</creatorcontrib><creatorcontrib>Guimarães, Adriana G</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pina, Lícia T S</au><au>Rabelo, Thallita K</au><au>Trindade, Gabriela G G</au><au>Almeida, Iggo K S</au><au>Oliveira, Marlange A</au><au>dos Santos, Priscila L</au><au>Souza, Diego Santos</au><au>de Menezes-Filho, José E R</au><au>de Vasconcelos, Carla Maria Lins</au><au>Santos, Sandra L</au><au>Scotti, Luciana</au><au>Scotti, Marcus T</au><au>Araújo, Adriano A S</au><au>Quintans, Jullyana S S</au><au>Quintans, Lucindo J</au><au>Guimarães, Adriana G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><date>2022-11-04</date><risdate>2022</risdate><volume>74</volume><issue>11</issue><spage>1629</spage><epage>1639</epage><pages>1629-1639</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>Abstract
Objectives
Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.
Methods
The γ-TPN/β-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, γ-TPN 50 mg/kg, γ-TPN/β-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-α and IL-1β levels, iNOS and c-Fos activity. The effects of γ-TPN on calcium channels were studied by patch-clamp and molecular docking.
Results
β-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1β, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.
Conclusion
These results indicate that the complexation of γ-TPN into β-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels.</abstract><cop>UK</cop><pub>Oxford University Press</pub><doi>10.1093/jpp/rgac052</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1643-5642</orcidid><orcidid>https://orcid.org/0000-0002-7197-0261</orcidid></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current) |
| title | γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block |
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