l-Borneol Exerted the Neuroprotective Effect by Promoting Angiogenesis Coupled With Neurogenesis via Ang1-VEGF-BDNF Pathway

Abstract

At present, Stroke is still one of the leading causes of population death worldwide and leads to disability. Traditional Chinese medicine plays an important role in the prevention or treatment of stroke. l-borneol, a traditional Chinese medicine, has been used in China to treat stroke for thousands of years. However, its mechanism of action is unclear. After cerebral ischemia, promoting angiogenesis after cerebral ischemia and providing nutrition for the infarct area is an important strategy to improve the damage in the ischemic area, but it is also essential to promote neurogenesis and replenish new neurons. Here, our research shows that l-borneol can significantly improve the neurological deficits of pMCAO model rats, reduce cerebral infarction, and improve the pathological damage of cerebral ischemia. and significantly increase serum level of Ang-1 and VEGF, and significantly decrease level of ACE and Tie2 to promote angiogenesis. PCR and WB showed the same results. Immunohistochemistry also showed that l-borneol can increase the number of CD34 positive cells, further verifying that l-borneol can play a neuroprotective effect by promoting angiogenesis after cerebral ischemia injury. In addition, l-borneol can significantly promote the expression level of VEGF, BDNF and inhibit the expression levels of TGF-β1 and MMP9 to promote neurogenesis. The above suggests that l-borneol can promote angiogenesis coupled neurogenesis by regulating Ang1-VEGF-BDNF to play a neuroprotective effect. Molecular docking also shows that l-borneol has a very high binding rate with the above target, which further confirmed the target of l-borneol to improve cerebral ischemic injury. These results provide strong evidence for the treatment of cerebral ischemia with l-borneol and provide reference for future research.

Progress in Borneol Intervention for Ischemic Stroke: A Systematic Review

“…In a BMECs model treated with OGD, borneol increased the expression of VEGF, reduced the expression of VEGFR1, and tended to increase the expression of VEGFR2 (Yu et al, 2019a). The latest research confirms that L-borneol can promote angiogenesis coupled neurogenesis by regulating Ang1-VEGF-BDNF to play a neuroprotective effect (Ma et al, 2021). In a tMCAO rat model, borneol significantly enhanced the expression of NGF, BDNF, GDNF, and VEGF mRNA after 48°h of reperfusion.…”

Identification of (-)-bornyl diphosphate synthase from Blumea balsamifera and its application for (-)-borneol biosynthesis in Saccharomyces cerevisiae

“…(-)-Borneol, a bicyclic monoterpene alcohol that is present in the essential oils of Blumea balsamifera (L.) DC., is widely used in the perfumery, cosmetics, and pharmaceutical industries [ 1 , 2 ]. It has been used medicinally for centuries in China for the treatment of stroke, and it is also used as a messenger drug to facilitate the transport of multiple drugs to specific sites by increasing blood-brain barrier permeability [ [3] , [4] , [5] ]. In addition, (-)-borneol and its derivatives exhibit a wide range of medicinal properties, such as anti-inflammatory, antimicrobial, and antiviral activities [ 6 , 7 ].…”

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

“…TTC can be reduced to 1,3,5-triphenylformazan by dehydrogenase in normal brain tissue and is red, while infarcted cells lose vitality and are white or ivory [ 11 ]. Figures 1(a) and 1(b) show that no infarction area was observed in the sham group (0.000 ± 0.000).…”

“…In the ischemic state, brain tissue is insufficiently supplied with oxygen and nutrients due to restrained and reduced blood flow, which results in a series of inflammatory responses, severe oxidative stress, neuronal damage, and apoptosis [18,19]. CI has a high rate of disability and mortality, the incidence of CI is on the rise, and there is no optimal treatment strategy [11,20]. In recent years, it has been reported that Chinese herbal medicines and their components, including AR, PR, and SR, can relieve neurological deficits and promote angiogenesis with low toxicity and few side effects, exerting a good neuroprotective effect in the context of CI [21][22][23].…”