Abstract
Previous studies have demonstrated that total flavonoid extracts from Caragana sinica (TFC) exert multiple therapeutic effects, promote blood flow, and exhibit anti-inflammatory and antioxidant properties. The present study aimed to investigate whether TFC promotes angiogenesis and exerts neuroprotective effects in a rat model of transient middle cerebral artery occlusion (tMCAO). Male Wistar rats were subjected to tMCAO for 1.5 h, followed by 24 h of reperfusion. TFC (15, 30, 60 mg/kg) was administered for 14 days. Evaluations of neurological function were performed following reperfusion, and infarct volumes were assessed in brain slices stained with 2,3,5-triphenyltetrazolium chloride (TTC). Our results indicated that TFC significantly attenuated cerebral infarct volume and neurological deficits following tMCAO. Laser Doppler, micro-PET/CT, and MRI analyses further demonstrated that TFC reduced infarct volume and enhanced cerebral blood flow in a dose-dependent manner, with the most significant effects occurring at a concentration of 60 mg/kg. Significant up-regulation of CD31, VEGF, Ang-1, HIF-1α, delta-like 4 (Dll4), and Notch1 expression was also observed in the experimental groups, relative to that in the vehicle group. In summary, the results of the present study indicate that TFC (15, 30, 60 mg/kg) attenuates neurological deficits, reduces infarct volume, and promotes angiogenesis following MCAO in a concentration-dependent manner, likely via increases in the expression of CD31, VEGF, Ang-1, HIF-1α, Dll4, and Notch1. Further studies are required to determine the clinical usefulness and potential mechanisms of TFC in patients with cerebral focal ischemic stroke.
Highlights
Stroke is the second leading cause of death worldwide
Significant differences in rCBF were observed between sham-operated and MCAO rats (Figure 2C, ∗∗∗p < 0.0001). These findings indicate that rat models of cerebral ischemia-reperfusion injury were successfully established, approximately 15% of rats in each group were excluded from data analysis due to failed surgery
Our analysis revealed that total flavonoid extracts from Caragana sinica (TFC) treatment at a concentration of 60 mg/kg can significantly improve neurological function and enhance cerebral perfusion when administered after transient MCAO in rats, similar to effects previously observed following treatment with puerarin (Lim et al, 2013; Wu et al, 2014)
Summary
Stroke is the second leading cause of death worldwide. As most cases of stroke occur due to ischemia, the need for more effective treatment strategies for ischemic stroke remains urgent (Bacigaluppi et al, 2008). Blood supply is severely reduced in the affected areas, eventually leading to cell death/apoptosis due to a lack of oxygen and nutrients (Plate, 1999). Accumulating evidence demonstrates that ischemic brain injury can be attenuated by restoring cerebral blood flow and rescuing dying neurons (Matsumoto et al, 1990; Zhang et al, 2002; Hoang et al, 2009). Recent research has focused on the development of agents that induce angiogenesis and exert neuroprotective effects in an effort to cure ischemic stroke. Natural compounds such as medicinal herbs, which are associated with fewer adverse effects than standard medications, may allow for safe and effective induction of angiogenesis and neuroprotection (Pierre et al, 1999)
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