Mechanism of action involved in the anxiolytic-like effects of Hibalactone isolated from Hydrocotyle umbellata L.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2022-07-01 DOI:10.1016/j.jtcme.2021.08.012

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

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引用次数: 1

Abstract

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-HT_1A receptor and the benzodiazepine site of GABA_A 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 GABA_A receptor.

Conclusion

Together, the results presented herein suggest that activation of the benzodiazepine site of the GABA_A receptor contributes to the anxiolytic-like effect of HB.

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从伞形花中分离得到的Hibalatone的抗焦虑作用机制。

背景和目的木脂素（HB）是一种木脂素，与伞形花的抗焦虑作用有关。然而，需要更好地了解这种木脂素的作用机制，以支持该物种的民族药理学用途。本工作旨在通过体内和计算机分析来评估HB在其抗焦虑样作用中的作用机制。实验方法采用光暗盒法（LDB）和升高加迷宫法（EPM）评价HB对小鼠的影响。评估5-HT1A受体和GABAA受体的苯二氮卓位点的参与，以研究其可能的作用机制。使用计算机工具来更好地阐明乙肝的抗焦虑作用。结果在LDB和EPM测试中，33 mg/kg剂量的乙肝口服治疗显示出抗焦虑的作用。除此之外，该治疗改变了行为学参数、低头频率和伸展注意姿势（SAP），这对更好地描述HB的抗焦虑特征很重要。氟马西尼（2 mg/kg）预处理恢复了HB对LDB和EPM测试的抗焦虑作用。另一方面，用NAN-190（0.5mg/kg）预处理没有恢复观察到的活性。计算机预测揭示了HB增加GABA能神经传递的潜力。药效团建模和对接模拟表明，HB可能与α1β2γ2 GABAA受体相互作用。结论本文的研究结果表明，GABAA受体苯二氮卓类位点的激活有助于HB的抗焦虑作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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