α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabissativa

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 IC(50) values of 3.0 ± 0.37 and 5.5 ± 0.28 μg/ml, respectively. These were better than the standard drug, acarbose (IC(50) 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 IC(50) 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.