一种标准化的复方草药制剂 POL-6 通过调节 GABA 受体信号通路中 Gabra1、Gabra2、Gabra3、Gabra4、Gabra5 基因的表达，减轻大鼠酒精戒断焦虑。
A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABA receptor signaling pathway in rats.
机构信息
Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, 173234, India.
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173229, India.
出版信息
BMC Complement Med Ther. 2021 Jan 6;21(1):13. doi: 10.1186/s12906-020-03181-2.
BACKGROUND
Alcohol abuse is a major problem worldwide and it affects people's health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6-24 h after the last alcohol ingestion.
METHODS
The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals' free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABA receptor subunits in the amygdala and hippocampus.
RESULTS
Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats.
CONCLUSION
The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.
背景
酗酒是一个全球性的主要问题，它影响人们的健康和经济。由于酒精戒断，会出现酒精摄入的复发。酒精戒断焦虑样行为是在最后一次饮酒后 6-24 小时出现的一种症状。
方法
本研究旨在探索标准化复方草药制剂 POL-6 对 Wistar 大鼠乙醇戒断焦虑的保护作用。POL-6 通过混合六种植物的干提取物 Bacopa monnieri、Hypericum perforatum、Centella asiatica、Withania somnifera、Camellia sinesis 和 Ocimum sanctum，按 2:1:2:2:1:2 的比例制备。POL-6 通过 LC-MS、HPLC 和 HPTLC 进行植物化学特征分析。使用双瓶选择饮酒范式模型测试 POL-6 对酒精戒断焦虑的影响，该模型使动物在 15 天内自由选择酒精和水。第 16 天停止饮酒，给予 POL-6（20、50 和 100mg/kg，口服）、地西泮（2mg/kg）治疗。使用 EPM 和 LDT 测试行为参数。第 18 天从大鼠眼眶后窦采集血液，研究酒精标志物 ALT、AST、ALP 和 GGT。研究结束时，处死动物并分离大脑，以探索 POL-6 对杏仁核和海马 GABA 受体亚基 mRNA 表达的影响。
结果
植物化学特征分析表明，POL-6 含有主要的植物成分，如醉茄内酯 A、槲皮素、儿茶素、芦丁、咖啡酸和 β-谷甾醇。体内研究表明，POL-6 在酒精戒断中具有抗焦虑作用。对分离的脑组织进行基因表达研究表明，POL-6 可使大鼠杏仁核和海马中的 GABA 能传递正常化。
结论
该研究得出结论，POL-6 可能具有治疗乙醇依赖的潜力。
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