α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabis sativa.
α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabis sativa.
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DOI：
10.1016/j.crfs.2022.07.002
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发表时间：
2022
影响因子：
6.3
通讯作者：
Panichayupakaranant, Pharkphoom
中科院分区：
文献类型：
--
作者：
Suttithumsatid, Wiwit;Shah, Muhammad Ajmal;Bibi, Shabana;Panichayupakaranant, Pharkphoom
据报道，大麻的两种主要大麻素，即大麻二酚（CBD）和四氢大麻酚（THC）已在临床前和临床研究中用作糖尿病治疗的替代药物。然而，它们的作用机制仍不清楚。因此，本研究旨在评估 THC、CBD 和标准化大麻素提取物的 α-葡萄糖苷酶抑制活性。根据计算机研究，THC 产生氢键和范德华相互作用，而 CBD 仅与目标 α-葡萄糖苷酶蛋白的功能残基表现出范德华相互作用，具有良好的结合能，分别为 -7.5 和 -6.9 kcal/mol。此外，它们都表现出优异的药代动力学特征，并且在致瘤和生殖作用方面的毒性较小。此外，基于α-葡萄糖苷酶的体外酶测定表明，THC和CBD表现出良好的抑制活性，IC50值分别为3.0±0.37和5.5±0.28μg/ml。这些优于标准药物阿卡波糖（IC50 为 488.6 ± 10.23 μg/ml）。此外，两种标准化大麻素提取物 SCE-I（苜蓿叶提取物）和 SCE-II（苜蓿花序提取物）表现出比 THC 和 CBD 更强的抑制活性，IC50 值分别为 1.2 ± 0.62 和 0.16 ± 0.01 μg/ml。本研究提供了第一个证据，表明含有 THC 和 CBD 的标准化大麻素提取物在作为 α-葡萄糖苷酶抑制剂的应用中比 CBD 和 THC 具有更大的潜力。计算机研究表明 THC 和 CBD 对 α-葡萄糖苷酶的抑制作用。 THC 和 CBD 表现出良好的药代动力学特征和低毒性。体外研究证实了THC和CBD对α-葡萄糖苷酶的抑制作用。标准化大麻素提取物显示出比 THC 和 CBD 更高的抑制效果。
Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of −7.5 and −6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in vitro assay on α-glucosidase revealed that THC and CBD exhibited good inhibitory activity, with the IC50 values of 3.0 ± 0.37 and 5.5 ± 0.28 μg/ml, respectively. These were better than the standard drug, acarbose (IC50 of 488.6 ± 10.23 μg/ml). Furthermore, two standardized cannabinoid extracts, SCE-I (C. sativa leaf extract) and SCE-II (C. sativa inflorescence extract) exhibited stronger inhibitory activity than THC and CBD, with the IC50 values of 1.2 ± 0.62 and 0.16 ± 0.01 μg/ml, respectively. The present study provides the first evidence that the standardized cannabinoid extracts containing THC and CBD have greater potential than CBD and THC in application as an α-glucosidase inhibitor. In silico study illustrated the inhibitory action of THC and CBD on α-glucosidase. THC and CBD exhibited good pharmacokinetic profiles with low toxicity. In vitro study confirmed the inhibitory effect of THC and CBD against α-glucosidase. Standardized cannabinoid extracts showed higher inhibitory effect than THC and CBD.
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