Protective effect of borneol combined with safflower on neurovascular unit in rats with ischemic stroke

Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.