叶绿醇增强卡马西平和地西泮对ptz诱导的雏鸡惊厥的抗惊厥作用,可能通过电压门控钠通道和GABAA相互作用途径

IF 4.2 4区 医学 Q2 CHEMISTRY, MEDICINAL
Md. Torequl Islam, Shoyaeb Ahammed, Md. Sakib Al Hasan, Mohammad Y. Alshahrani, Raihan Chowdhury, Salehin Sheikh, Emon Mia, Fazley Rohan, Imam Hossen Rakib, Md. Sabbir Hosain, Proma Mandal
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引用次数: 0

摘要

叶绿素衍生的二萜叶绿醇(PHY)具有多种生物效应,包括实验动物的神经保护作用。本研究旨在通过动物实验和计算机实验来评价PHY的抗惊厥作用及其可能的作用机制。为此,我们对雏鸡进行了戊四唑(PTZ)诱导的惊厥试验,并对GABAA受体亚基和电压门控钠通道(VGSC)受体进行了硅研究。在25、50和75 mg/kg的情况下,用或不加标准药物地西泮(DZP: 5 mg/kg)和卡马西平(CAR: 80 mg/kg)的情况下,用载具作为对照,检测PHY。根据OECD指南,通过给予PHY (500-2000 mg/kg, p.o)并监测48小时的死亡率、毒理学体征和行为变化来评估雏鸡的急性口服毒性。PHY表现出剂量依赖性的抗惊厥作用,在75mg /kg剂量下显著增加潜伏期,减少惊厥频率和持续时间。PHY (75 mg/kg)联合CAR和DZP对惊厥频率和持续时间的减少最为有效,表明具有协同作用。在雏鸡中进行的急性毒性试验证实高达2000毫克/公斤是安全的。硅研究表明,PHY与GABAA受体(-6.5 kcal/mol)和VGSC (-7.0 kcal/mol)具有良好的结合亲和力,可能通过GABAA能和钠通道调节来促进其抗惊厥作用。PHY显示出显著的抗惊厥活性,可能通过GABAA和VGSC调节,需要进一步研究以阐明其机制并评估其在耐药惊厥治疗中的辅助潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Phytol Enhances Anticonvulsant Effect of Carbamazepine and Diazepam Against PTZ-Induced Convulsion in Chicks, Possibly Through Voltage-Gated Sodium Channel and GABAA Interaction Pathways

Phytol Enhances Anticonvulsant Effect of Carbamazepine and Diazepam Against PTZ-Induced Convulsion in Chicks, Possibly Through Voltage-Gated Sodium Channel and GABAA Interaction Pathways

Phytol Enhances Anticonvulsant Effect of Carbamazepine and Diazepam Against PTZ-Induced Convulsion in Chicks, Possibly Through Voltage-Gated Sodium Channel and GABAA Interaction Pathways

Phytol Enhances Anticonvulsant Effect of Carbamazepine and Diazepam Against PTZ-Induced Convulsion in Chicks, Possibly Through Voltage-Gated Sodium Channel and GABAA Interaction Pathways

The chlorophyll-derived diterpenoid phytol (PHY) is evident for its diverse biological effects, including neuroprotective activities in experimental animals. This study aims at the evaluation of anticonvulsant effects along with the possible mechanism of action of PHY through animal and in silico studies. For this, we performed pentylenetetrazole (PTZ)-induced convulsion tests in chicks and in silico studies against GABAA receptor subunits and voltage-gated sodium channel (VGSC) receptors. PHY was tested at 25, 50, and 75 mg/kg with or without the standard drugs diazepam (DZP: 5 mg/kg) and carbamazepine (CAR: 80 mg/kg) using a vehicle as a control. Acute oral toxicity was evaluated in chicks per OECD guidelines by administering PHY (500–2000 mg/kg, p.o.) and monitoring for 48 h for mortality, toxicological signs, and behavioral changes. PHY exhibited a dose-dependent anticonvulsant effect, significantly increasing latency and reducing convulsion frequency and duration at 75 mg/kg. PHY (75 mg/kg) combined with CAR and DZP showed the most potent reduction in convulsion frequency and duration, indicating a synergistic effect. Acute toxicity tests in chicks confirmed safety up to 2000 mg/kg. In silico studies demonstrated that PHY had good binding affinity with both the GABAA receptor (–6.5 kcal/mol) and VGSC (–7.0 kcal/mol), potentially contributing to its anticonvulsant action through GABAergic and sodium channel modulation. PHY showed significant anticonvulsant activity, likely via GABAA and VGSC modulation, warranting further studies to clarify its mechanisms and assess its adjunct potential in drug-resistant convulsion management.

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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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