从莲属植物中分离得到的二萘并二苯并吡咯 G 的体内镇痛、抗炎和镇静活性及分子对接研究。
In vivo analgesic, anti-inflammatory, and sedative activity and a molecular docking study of dinaphthodiospyrol G isolated from Diospyros lotus.
机构信息
Department of Chemistry, University of Swabi Anbar KPK, Swabi, Pakistan.
Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Al Ain, UAE.
出版信息
BMC Complement Med Ther. 2020 Jul 25;20(1):237. doi: 10.1186/s12906-020-03030-2.
BACKGROUND
Analgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product from Diospyros lotus, was tested for the aforementioned bioactivities.
OBJECTIVES
To evaluate analgesic, anti-inflammatory, and sedative potential of D. lotus extracts in animal paradigms using BALB/c mice as experimental model.
METHODS
Analgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction of D. lotus were evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound 1. Compound 1 was also subjected to molecular modeling studies against cyclooxygenase enzymes.
RESULTS
Results from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p < 0.001) and dose-dependent antinociceptive and sedative effects were demonstrated by the isolated compound. Molecular docking and dynamics simulation studies of the isolated compound against cyclooxygenase enzyme indicated that compound 1 forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor.
CONCLUSIONS
Compound 1 exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use of D. lotus in the treatment of inflammation, pain, and insomnia.
背景
有镇痛、抗炎和镇静作用的药物都有潜在的副作用，如消化性溃疡和成瘾等。在这方面，正在进行研究以寻找安全、有效且经济的药物，避免这些副作用。在这项研究中，对来自柿树的一种分离天然产物进行了测试，以评估其上述生物活性。
目的
使用 BALB/c 小鼠作为实验模型，评估柿树提取物的镇痛、抗炎和镇静作用。
方法
用不同的实验程序评估从柿树的氯仿部分分离得到的二萘并[g,h]色烯二醇 G（1）的镇痛、抗炎和镇静活性。抗炎作用通过角叉菜胶和组胺诱导的足肿胀来评估，而镇痛作用通过热板测痛仪来量化。另一方面，通过化合物 1 对动物的运动效应的筛选来确定其镇静作用。还对化合物 1 进行了针对环氧化酶酶的分子建模研究。
结果
本研究结果表明，提取物缺乏抗炎和镇痛作用，但具有显著的镇静作用，而所测试的化合物在角叉菜胶和组胺试验中分别对足肿胀的抑制率为 55.23%和 78.34%。分离出的化合物表现出显著的（p<0.001）、剂量依赖性的镇痛和镇静作用。对分离出的化合物与环氧化酶酶的分子对接和动力学模拟研究表明，化合物 1 与靶受体活性位点的关键残基形成特异性相互作用，这验证了该化合物作为环氧化酶抑制剂的潜在用途。
结论
化合物 1 表现出显著的镇痛、抗炎和镇静活性。这些发现有力地证明了柿树传统上用于治疗炎症、疼痛和失眠的用途。
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