Study On Anti-stroke Activity Of Two Different Types Of Cannabidiol Based On Metabonomics

Blockage or rupture of blood vessels in the brain induced stroke,which was the leading cause of death and disability.Cannabidiol(CBD)showed multiple neuroprotection on ischemic stroke due to its anti-oxidation and anti-inflammatory activities.However,the poor water solubility of CBD greatly limited its application,so a water-soluble CBD were prepared and explored for it’s anti-stroke activity.In vitro levels,the oxyglucose deprivation and reperfusion(OGD/R)model was established to compare the anti-stroke activities of water-soluble CBD and non-water-soluble CBD.The results indicated thatwater-soluble CBD significantly increased the activities of cellular antioxidant capacity by increasing the activity of superoxide dismutase(SOD),the content of glutathione(GSH),and reducing the content of intracellular reactive oxygen species(ROS).In addition,it could effectively inhibit the nuclear translocation of the nuclear factor-κB p65(NF-κB p65)and reduce the expression of cyclooxygenase-2(COX-2)and high mobility group protein(HMGB1),thereby inhibiting inflammatory reaction of stroke.Watersoluble CBD showed better anti-stroke activity than non-water-insoluble CBD.In vivo levels,the rat middle cerebral artery occlusion(MCAO)model was established to investigate the antistroke activity of water-soluble CBD in vivo.TTC(2,3,5-triphenyltetrazolium chloride)staining of brain tissues showed that the infarct area of brain tissue was decreased significantly after water-soluble CBD treatment.Histopathological analysis revealed that brain tissue injury caused by ischemia-reperfusion was significantly reduced after CBD treatment.The increase of GSH and SOD in serum and the decrease of COX-2 and HMGB1 expression in brain tissue indicated the antioxidant and anti-inflammatory activities of CBD contributing to its anti-stroke effect.A UPLC-MS based metabolomics approach was used to screen and identify biomarkers and metabolic pathways related to the anti-stroke activity of CBD.The results showed that CBD exhibited anti-stroke effect by regulating oxidative phosphorylation,apoptosis,purine metabolism,citric acid cycle(TCA cycle),amino acid metabolism and lipid metabolism.In conclusion,CBD could effectively alleviate the damage caused by ischemic stroke,and watersoluble CBD overcame the solubility defect and showed better anti-stroke activity than non water-soluble CBD.