Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved

Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as “quebra-faca”. In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potent...

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Veröffentlicht in:Journal of ethnopharmacology 2018-07, Vol.221 (NA), p.65-76
Hauptverfasser: Oliveira Júnior, Raimundo Gonçalves de, Ferraz, Christiane Adrielly Alves, Silva, Juliane Cabral, de Andrade Teles, Roxana Braga, Silva, Mariana Gama, Diniz, Tâmara Coimbra, dos Santos, Uiliane Soares, de Souza, Ana Valéria Vieira, Nunes, Carlos Eduardo Pereira, Salvador, Marcos José, Lorenzo, Vitor Prates, Quintans Júnior, Lucindo José, Almeida, Jackson Roberto Guedes da Silva
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container_issue NA
container_start_page 65
container_title Journal of ethnopharmacology
container_volume 221
creator Oliveira Júnior, Raimundo Gonçalves de
Ferraz, Christiane Adrielly Alves
Silva, Juliane Cabral
de Andrade Teles, Roxana Braga
Silva, Mariana Gama
Diniz, Tâmara Coimbra
dos Santos, Uiliane Soares
de Souza, Ana Valéria Vieira
Nunes, Carlos Eduardo Pereira
Salvador, Marcos José
Lorenzo, Vitor Prates
Quintans Júnior, Lucindo José
Almeida, Jackson Roberto Guedes da Silva
description Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as “quebra-faca”. In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p 
doi_str_mv 10.1016/j.jep.2018.04.009
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In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p &lt; 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole − 21.42%, spathulenol – 15.47%, p-cymene – 12.41% and caryophyllene oxide – 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p &lt; 0.05), indicating possible involvement of GABAA receptors. Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used. [Display omitted]</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2018.04.009</identifier><identifier>PMID: 29627297</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Anxiety ; Essential oil ; Insomnia ; Medicinal plants ; Pain</subject><ispartof>Journal of ethnopharmacology, 2018-07, Vol.221 (NA), p.65-76</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-2b946172c323748aa9ac2e5dfd58284ed97f74b79585b73bcfb69d093f613a0d3</citedby><cites>FETCH-LOGICAL-c495t-2b946172c323748aa9ac2e5dfd58284ed97f74b79585b73bcfb69d093f613a0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378874118300382$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29627297$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oliveira Júnior, Raimundo Gonçalves de</creatorcontrib><creatorcontrib>Ferraz, Christiane Adrielly Alves</creatorcontrib><creatorcontrib>Silva, Juliane Cabral</creatorcontrib><creatorcontrib>de Andrade Teles, Roxana Braga</creatorcontrib><creatorcontrib>Silva, Mariana Gama</creatorcontrib><creatorcontrib>Diniz, Tâmara Coimbra</creatorcontrib><creatorcontrib>dos Santos, Uiliane Soares</creatorcontrib><creatorcontrib>de Souza, Ana Valéria Vieira</creatorcontrib><creatorcontrib>Nunes, Carlos Eduardo Pereira</creatorcontrib><creatorcontrib>Salvador, Marcos José</creatorcontrib><creatorcontrib>Lorenzo, Vitor Prates</creatorcontrib><creatorcontrib>Quintans Júnior, Lucindo José</creatorcontrib><creatorcontrib>Almeida, Jackson Roberto Guedes da Silva</creatorcontrib><title>Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as “quebra-faca”. In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p &lt; 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole − 21.42%, spathulenol – 15.47%, p-cymene – 12.41% and caryophyllene oxide – 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p &lt; 0.05), indicating possible involvement of GABAA receptors. Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used. 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In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p &lt; 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole − 21.42%, spathulenol – 15.47%, p-cymene – 12.41% and caryophyllene oxide – 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p &lt; 0.05), indicating possible involvement of GABAA receptors. Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used. [Display omitted]</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>29627297</pmid><doi>10.1016/j.jep.2018.04.009</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Anxiety
Essential oil
Insomnia
Medicinal plants
Pain
title Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved
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