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从L.中分离出的日巴内酯产生抗焦虑样作用的作用机制

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

作者信息

Gabriel de Oliveira Matheus, Kelle da Silva Moreira Lorrane, Turones Larissa Cordova, de Souza Almeida Dionys, Martins Aline Nazareth, Silva Oliveira Thiago Levi, Barreto da Silva Vinicius, Borges Leonardo Luiz, Costa Elson Alves, Realino de Paula José

机构信息

Faculdade de Farmácia, Universidade Federal de Goiás, Av. Universitária com 1 Avenida s/n, Setor Universitário, 74605-220, Goiânia, Goiás, Brazil.

Laboratório de Farmacologia de Produtos Naturais e Sintéticos, Universidade Federal de Goiás, Avenida Esperança, s/n Campus Samambaia, 74690-900, Goiânia, Goiás, Brazil.

出版信息

J Tradit Complement Med. 2021 Sep 11;12(4):318-329. doi: 10.1016/j.jtcme.2021.08.012. eCollection 2022 Jul.

DOI:10.1016/j.jtcme.2021.08.012
PMID:35747359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9209824/
Abstract

BACKGROUND AND AIM

Hibalactone (HB) is a lignan related to the anxiolytic-like effects of 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 and 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 receptor and the benzodiazepine site of GABA receptor was evaluated to investigate the possible mechanism of action. 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. predictions revealed the potential of HB to increase GABAergic neurotransmission. Pharmacophore modelling and docking simulations showed that HB might interact with the α1β2γ2 GABA receptor.

CONCLUSION

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

摘要

背景与目的

水紫树内酯（HB）是一种与木兰科植物的抗焦虑样作用相关的木脂素。然而，有必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应用。这项工作旨在通过[具体方法1]和[具体方法2]分析来评估HB产生抗焦虑样作用的作用机制。

实验过程

在明暗箱（LDB）和高架十字迷宫（EPM）试验中评估了HB对小鼠的影响。评估了5-羟色胺（5-HT）受体和GABA受体的苯二氮䓬位点的参与情况，以研究可能的作用机制。使用[具体工具]来更好地阐明HB的抗焦虑样作用。

结果

以33mg/kg的剂量口服HB在LDB和EPM试验中显示出抗焦虑样作用。除此之外，该处理改变了行为学参数、头部下探频率和伸展注意姿势（SAP），这对于更好地描述HB的抗焦虑特征很重要。用氟马西尼（2mg/kg）预处理可逆转HB在LDB和EPM试验中的抗焦虑样作用。另一方面，用NAN - 190（0.5mg/kg）预处理并未逆转所观察到的活性。[具体分析方法]预测显示HB具有增加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 GABA受体相互作用。

结论

总之，本文给出的结果表明GABA受体苯二氮䓬位点的激活有助于HB的抗焦虑样作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/011f654a4ee3/fx4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/f5b69c7a74ba/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/c476ce6a832f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/db7483a3d198/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/9a56633e4c51/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/f60d58460347/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/c0cffaa757e1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/704a69e6304e/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/ec810b476f7a/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/b11aba47f2d4/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/c9fb87167f13/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/9dadc21d18c4/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/82aadbf56ad1/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/f41b8451d631/fx2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/88d0ac9f23ba/fx3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/011f654a4ee3/fx4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/f5b69c7a74ba/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/c476ce6a832f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/db7483a3d198/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/9a56633e4c51/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/f60d58460347/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/c0cffaa757e1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/704a69e6304e/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/ec810b476f7a/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/b11aba47f2d4/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/c9fb87167f13/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/9dadc21d18c4/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/82aadbf56ad1/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/f41b8451d631/fx2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/88d0ac9f23ba/fx3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6182/9209824/011f654a4ee3/fx4.jpg

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