Matheus Gabriel de Oliveira , Lorrane Kelle da Silva Moreira , Larissa Cordova Turones , Dionys de Souza Almeida , Aline Nazareth Martins , Thiago Levi Silva Oliveira , Vinicius Barreto da Silva , Leonardo Luiz Borges , Elson Alves Costa , José Realino de Paula
{"title":"从伞形花中分离得到的Hibalatone的抗焦虑作用机制。","authors":"Matheus Gabriel de Oliveira , Lorrane Kelle da Silva Moreira , Larissa Cordova Turones , Dionys de Souza Almeida , Aline Nazareth Martins , Thiago Levi Silva Oliveira , Vinicius Barreto da Silva , Leonardo Luiz Borges , Elson Alves Costa , José Realino de Paula","doi":"10.1016/j.jtcme.2021.08.012","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aim</h3><p>Hibalactone (HB) is a lignan related to the anxiolytic-like effects of <em>Hydrocotyle umbellata</em> L. However, there is a need to understand better the mechanism of action of this lignan to support the ethnopharmacological uses of the species. This work aimed to evaluate by <em>in vivo</em> and <em>in silico</em> analysis the mechanism of action of HB involved in its anxiolytic-like effects.</p></div><div><h3>Experimental procedure</h3><p>The effects of HB in mice were evaluated on light-dark box (LDB) and elevated plus maze (EPM) tests. The participation of 5-HT<sub>1A</sub> receptor and the benzodiazepine site of GABA<sub>A</sub> receptor was evaluated to investigate the possible mechanism of action. <em>In silico</em> tools were used to better elucidate the anxiolytic-like effects of HB.</p></div><div><h3>Results</h3><p>Oral treatment with HB at a dose of 33 mg/kg showed an anxiolytic-like effect in the LDB and EPM tests. Besides that, the treatment altered the ethological parameters, frequency of head dips, and stretched-attend postures (SAP), important to better describe the anxiolytic profile of HB. Pretreatment with flumazenil (2 mg/kg) reverted the anxiolytic-like effect of HB on LDB and EPM tests. On the other hand, pretreatment with NAN-190 (0.5 mg/kg) not reverted the activity observed. <em>In silico</em> predictions revealed the potential of HB to increase GABAergic neurotransmission. Pharmacophore modelling and docking simulations showed that HB might interact with the α1β2γ2 GABA<sub>A</sub> receptor.</p></div><div><h3>Conclusion</h3><p>Together, the results presented herein suggest that activation of the benzodiazepine site of the GABA<sub>A</sub> receptor contributes to the anxiolytic-like effect of HB.</p></div>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jtcme.2021.08.012","citationCount":"1","resultStr":"{\"title\":\"Mechanism of action involved in the anxiolytic-like effects of Hibalactone isolated from Hydrocotyle umbellata L.\",\"authors\":\"Matheus Gabriel de Oliveira , Lorrane Kelle da Silva Moreira , Larissa Cordova Turones , Dionys de Souza Almeida , Aline Nazareth Martins , Thiago Levi Silva Oliveira , Vinicius Barreto da Silva , Leonardo Luiz Borges , Elson Alves Costa , José Realino de Paula\",\"doi\":\"10.1016/j.jtcme.2021.08.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and aim</h3><p>Hibalactone (HB) is a lignan related to the anxiolytic-like effects of <em>Hydrocotyle umbellata</em> L. However, there is a need to understand better the mechanism of action of this lignan to support the ethnopharmacological uses of the species. This work aimed to evaluate by <em>in vivo</em> and <em>in silico</em> analysis the mechanism of action of HB involved in its anxiolytic-like effects.</p></div><div><h3>Experimental procedure</h3><p>The effects of HB in mice were evaluated on light-dark box (LDB) and elevated plus maze (EPM) tests. The participation of 5-HT<sub>1A</sub> receptor and the benzodiazepine site of GABA<sub>A</sub> receptor was evaluated to investigate the possible mechanism of action. <em>In silico</em> tools were used to better elucidate the anxiolytic-like effects of HB.</p></div><div><h3>Results</h3><p>Oral treatment with HB at a dose of 33 mg/kg showed an anxiolytic-like effect in the LDB and EPM tests. Besides that, the treatment altered the ethological parameters, frequency of head dips, and stretched-attend postures (SAP), important to better describe the anxiolytic profile of HB. Pretreatment with flumazenil (2 mg/kg) reverted the anxiolytic-like effect of HB on LDB and EPM tests. On the other hand, pretreatment with NAN-190 (0.5 mg/kg) not reverted the activity observed. <em>In silico</em> predictions revealed the potential of HB to increase GABAergic neurotransmission. Pharmacophore modelling and docking simulations showed that HB might interact with the α1β2γ2 GABA<sub>A</sub> receptor.</p></div><div><h3>Conclusion</h3><p>Together, the results presented herein suggest that activation of the benzodiazepine site of the GABA<sub>A</sub> receptor contributes to the anxiolytic-like effect of HB.</p></div>\",\"PeriodicalId\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2022-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.jtcme.2021.08.012\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2225411021001048\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2225411021001048","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
Mechanism of action involved in the anxiolytic-like effects of Hibalactone isolated from Hydrocotyle umbellata L.
Background and aim
Hibalactone (HB) is a lignan related to the anxiolytic-like effects of Hydrocotyle umbellata L. However, there is a need to understand better the mechanism of action of this lignan to support the ethnopharmacological uses of the species. This work aimed to evaluate by in vivo and in silico analysis the mechanism of action of HB involved in its anxiolytic-like effects.
Experimental procedure
The effects of HB in mice were evaluated on light-dark box (LDB) and elevated plus maze (EPM) tests. The participation of 5-HT1A receptor and the benzodiazepine site of GABAA receptor was evaluated to investigate the possible mechanism of action. In silico tools were used to better elucidate the anxiolytic-like effects of HB.
Results
Oral treatment with HB at a dose of 33 mg/kg showed an anxiolytic-like effect in the LDB and EPM tests. Besides that, the treatment altered the ethological parameters, frequency of head dips, and stretched-attend postures (SAP), important to better describe the anxiolytic profile of HB. Pretreatment with flumazenil (2 mg/kg) reverted the anxiolytic-like effect of HB on LDB and EPM tests. On the other hand, pretreatment with NAN-190 (0.5 mg/kg) not reverted the activity observed. In silico predictions revealed the potential of HB to increase GABAergic neurotransmission. Pharmacophore modelling and docking simulations showed that HB might interact with the α1β2γ2 GABAA receptor.
Conclusion
Together, the results presented herein suggest that activation of the benzodiazepine site of the GABAA receptor contributes to the anxiolytic-like effect of HB.
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