Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection
Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolid...
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| Veröffentlicht in: | Life sciences (1973) 2021-01, Vol.265, p.118742, Article 118742 |
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| creator | de Souza, Eloísa Portugal Barros Silva Soares Gomes, Marcelo Vinicius Lins Dantas dos Santos Lima, Bruno Silva, Luiz André Santos Shanmugan, Saravanan Cavalcanti, Marcelo Duarte de Albuquerque Júnior, Ricardo Luiz Cavalcanti de Souza Carvalho, Flavio Machado Marreto, Ricardo Neves de Lima, Claudio Moreira Júnior, Lucindo José Quintans de Souza Araújo, Adriano Antunes |
| description | Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.
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| doi_str_mv | 10.1016/j.lfs.2020.118742 |
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[Display omitted]</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2020.118742</identifier><identifier>PMID: 33181176</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Anti-inflammatory agents ; Anti-Inflammatory Agents - pharmacology ; Anti-Ulcer Agents - pharmacology ; Arthritis ; Arthritis - drug therapy ; Arthritis, Experimental - drug therapy ; beta-Cyclodextrins - pharmacology ; Cartilage ; Cell Line ; Cyclodextrins ; Cytotoxicity ; Ethanol ; Freeze drying ; Gastric Mucosa - metabolism ; Gastric ulcer ; Inclusion complexes ; Indomethacin ; Indomethacin - pharmacology ; Inflammation ; Inflammatory diseases ; Joint diseases ; Joints ; Leukocyte migration ; Leukocytes (neutrophilic) ; Male ; Medical treatment ; Mice ; Nerolidol ; Neutrophils ; NMR ; Nonsteroidal anti-inflammatory drugs ; Nuclear magnetic resonance ; Plant Extracts - pharmacology ; Rheumatoid arthritis ; Sesquiterpenes - pharmacology ; Stomach - pathology ; Stomach Ulcer - chemically induced ; Terpene ; Toxicity ; Ulcers ; Zymosan ; β-Cyclodextrin</subject><ispartof>Life sciences (1973), 2021-01, Vol.265, p.118742, Article 118742</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Jan 15, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-f99c3208ef09983a29df1dedc76daa0aaff931a39b3f8a5171f5523025e8444f3</citedby><cites>FETCH-LOGICAL-c381t-f99c3208ef09983a29df1dedc76daa0aaff931a39b3f8a5171f5523025e8444f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320520314958$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33181176$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Souza, Eloísa Portugal Barros Silva Soares</creatorcontrib><creatorcontrib>Gomes, Marcelo Vinicius Lins Dantas</creatorcontrib><creatorcontrib>dos Santos Lima, Bruno</creatorcontrib><creatorcontrib>Silva, Luiz André Santos</creatorcontrib><creatorcontrib>Shanmugan, Saravanan</creatorcontrib><creatorcontrib>Cavalcanti, Marcelo Duarte</creatorcontrib><creatorcontrib>de Albuquerque Júnior, Ricardo Luiz Cavalcanti</creatorcontrib><creatorcontrib>de Souza Carvalho, Flavio Machado</creatorcontrib><creatorcontrib>Marreto, Ricardo Neves</creatorcontrib><creatorcontrib>de Lima, Claudio Moreira</creatorcontrib><creatorcontrib>Júnior, Lucindo José Quintans</creatorcontrib><creatorcontrib>de Souza Araújo, Adriano Antunes</creatorcontrib><title>Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.
[Display omitted]</description><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Ulcer Agents - pharmacology</subject><subject>Arthritis</subject><subject>Arthritis - drug therapy</subject><subject>Arthritis, Experimental - drug therapy</subject><subject>beta-Cyclodextrins - pharmacology</subject><subject>Cartilage</subject><subject>Cell Line</subject><subject>Cyclodextrins</subject><subject>Cytotoxicity</subject><subject>Ethanol</subject><subject>Freeze drying</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastric ulcer</subject><subject>Inclusion complexes</subject><subject>Indomethacin</subject><subject>Indomethacin - pharmacology</subject><subject>Inflammation</subject><subject>Inflammatory diseases</subject><subject>Joint diseases</subject><subject>Joints</subject><subject>Leukocyte migration</subject><subject>Leukocytes (neutrophilic)</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Mice</subject><subject>Nerolidol</subject><subject>Neutrophils</subject><subject>NMR</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Nuclear magnetic resonance</subject><subject>Plant Extracts - pharmacology</subject><subject>Rheumatoid arthritis</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Stomach - pathology</subject><subject>Stomach Ulcer - chemically induced</subject><subject>Terpene</subject><subject>Toxicity</subject><subject>Ulcers</subject><subject>Zymosan</subject><subject>β-Cyclodextrin</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rVDEUhoNY7LT6A9xIwPUd83FzP3AlpWqh6KZdh0xyYjPkJmOSGTr7_nBPmerS1eHA-7yH8xDynrM1Z3z4tF1HX9eCCdz5NPbiFVnhnDs2SP6arBgTfScFU-fkotYtY0ypUb4h51LyifNxWJGnH1ByDC7HbgPNdPZoY3bw2EpINCQb9zXkRG1edhEeKaQHkyxUalILXUg-mmUxLZcjNbaFQ2hHpKgp7aGEFipdsCxi2tGw7Eo-IPrLVGy3FNcGCOX0lpx5Eyu8e5mX5P7r9d3V9-7257ebqy-3nZUTb52fZ4vfTODZPE_SiNl57sDZcXDGMGO8nyU3ct5IPxnFR-6VEpIJBVPf915eko-nXjz9ew-16W3el4QntVBMjUIoMWCKn1K25FoLeL0rYTHlqDnTz971VqN3_exdn7wj8-Gleb9ZwP0j_orGwOdTAPC_Q4Ciqw2AKl0oKEG7HP5T_wfTfJbE</recordid><startdate>20210115</startdate><enddate>20210115</enddate><creator>de Souza, Eloísa Portugal Barros Silva Soares</creator><creator>Gomes, Marcelo Vinicius Lins Dantas</creator><creator>dos Santos Lima, Bruno</creator><creator>Silva, Luiz André Santos</creator><creator>Shanmugan, Saravanan</creator><creator>Cavalcanti, Marcelo Duarte</creator><creator>de Albuquerque Júnior, Ricardo Luiz Cavalcanti</creator><creator>de Souza Carvalho, Flavio Machado</creator><creator>Marreto, Ricardo Neves</creator><creator>de Lima, Claudio Moreira</creator><creator>Júnior, Lucindo José Quintans</creator><creator>de Souza Araújo, Adriano Antunes</creator><general>Elsevier Inc</general><general>Elsevier BV</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20210115</creationdate><title>Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection</title><author>de Souza, Eloísa Portugal Barros Silva Soares ; Gomes, Marcelo Vinicius Lins Dantas ; dos Santos Lima, Bruno ; Silva, Luiz André Santos ; Shanmugan, Saravanan ; Cavalcanti, Marcelo Duarte ; de Albuquerque Júnior, Ricardo Luiz Cavalcanti ; de Souza Carvalho, Flavio Machado ; Marreto, Ricardo Neves ; de Lima, Claudio Moreira ; Júnior, Lucindo José Quintans ; de Souza Araújo, Adriano Antunes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-f99c3208ef09983a29df1dedc76daa0aaff931a39b3f8a5171f5523025e8444f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Anti-inflammatory agents</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Ulcer Agents - pharmacology</topic><topic>Arthritis</topic><topic>Arthritis - drug therapy</topic><topic>Arthritis, Experimental - drug therapy</topic><topic>beta-Cyclodextrins - pharmacology</topic><topic>Cartilage</topic><topic>Cell Line</topic><topic>Cyclodextrins</topic><topic>Cytotoxicity</topic><topic>Ethanol</topic><topic>Freeze drying</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastric ulcer</topic><topic>Inclusion complexes</topic><topic>Indomethacin</topic><topic>Indomethacin - pharmacology</topic><topic>Inflammation</topic><topic>Inflammatory diseases</topic><topic>Joint diseases</topic><topic>Joints</topic><topic>Leukocyte migration</topic><topic>Leukocytes (neutrophilic)</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Mice</topic><topic>Nerolidol</topic><topic>Neutrophils</topic><topic>NMR</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Nuclear magnetic resonance</topic><topic>Plant Extracts - pharmacology</topic><topic>Rheumatoid arthritis</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Stomach - pathology</topic><topic>Stomach Ulcer - chemically induced</topic><topic>Terpene</topic><topic>Toxicity</topic><topic>Ulcers</topic><topic>Zymosan</topic><topic>β-Cyclodextrin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Souza, Eloísa Portugal Barros Silva Soares</creatorcontrib><creatorcontrib>Gomes, Marcelo Vinicius Lins Dantas</creatorcontrib><creatorcontrib>dos Santos Lima, Bruno</creatorcontrib><creatorcontrib>Silva, Luiz André Santos</creatorcontrib><creatorcontrib>Shanmugan, Saravanan</creatorcontrib><creatorcontrib>Cavalcanti, Marcelo Duarte</creatorcontrib><creatorcontrib>de Albuquerque Júnior, Ricardo Luiz Cavalcanti</creatorcontrib><creatorcontrib>de Souza Carvalho, Flavio Machado</creatorcontrib><creatorcontrib>Marreto, Ricardo Neves</creatorcontrib><creatorcontrib>de Lima, Claudio Moreira</creatorcontrib><creatorcontrib>Júnior, Lucindo José Quintans</creatorcontrib><creatorcontrib>de Souza Araújo, Adriano Antunes</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Souza, Eloísa Portugal Barros Silva Soares</au><au>Gomes, Marcelo Vinicius Lins Dantas</au><au>dos Santos Lima, Bruno</au><au>Silva, Luiz André Santos</au><au>Shanmugan, Saravanan</au><au>Cavalcanti, Marcelo Duarte</au><au>de Albuquerque Júnior, Ricardo Luiz Cavalcanti</au><au>de Souza Carvalho, Flavio Machado</au><au>Marreto, Ricardo Neves</au><au>de Lima, Claudio Moreira</au><au>Júnior, Lucindo José Quintans</au><au>de Souza Araújo, Adriano Antunes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2021-01-15</date><risdate>2021</risdate><volume>265</volume><spage>118742</spage><pages>118742-</pages><artnum>118742</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.
[Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>33181176</pmid><doi>10.1016/j.lfs.2020.118742</doi></addata></record> |
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| subjects | Animals Anti-inflammatory agents Anti-Inflammatory Agents - pharmacology Anti-Ulcer Agents - pharmacology Arthritis Arthritis - drug therapy Arthritis, Experimental - drug therapy beta-Cyclodextrins - pharmacology Cartilage Cell Line Cyclodextrins Cytotoxicity Ethanol Freeze drying Gastric Mucosa - metabolism Gastric ulcer Inclusion complexes Indomethacin Indomethacin - pharmacology Inflammation Inflammatory diseases Joint diseases Joints Leukocyte migration Leukocytes (neutrophilic) Male Medical treatment Mice Nerolidol Neutrophils NMR Nonsteroidal anti-inflammatory drugs Nuclear magnetic resonance Plant Extracts - pharmacology Rheumatoid arthritis Sesquiterpenes - pharmacology Stomach - pathology Stomach Ulcer - chemically induced Terpene Toxicity Ulcers Zymosan β-Cyclodextrin |
| title | Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection |
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