[Borneol promotes catalpol and puerarin crossing through blood-brain barrier in focal cerebral ischemic rats]

Zhongguo Zhong Yao Za Zhi. 2016 Nov;41(21):3988-3995. doi: 10.4268/cjcmm20162117.
[Article in Chinese]

Abstract

Previous studies showed that borneol could promote some drugs crossing through the blood-brain-barrier (BBB) at certain conditions. However, the mechanism has not been clarified yet. This study aimed to investigate the effect of bornrol on promoting catalpol and puerarin through BBB and explore the relevant mechanism. The focal cerebral ischemic rats were divided into 7 groups randomly and then were administered corresponding drugs: model group (M, solvent), catalpol-puerarin group (ZG, catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹), catalpol-puerarin-bornrol group(ZGB, catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹), catalpol-bornrol group(ZB, catalpol 45 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹), puerarin-bornrol group(GB, puerarin 200 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹), butoxamine-ZG group(BTX+ZG, butoxamine 1.5 mg•kg⁻¹+ catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹), and butoxamine-ZGB group(BTX+ZGB, butoxamine 1.5 mg•kg⁻¹+ catalpol 45 mg•kg⁻¹+puerarin 200 mg•kg⁻¹ +bornrol 200 mg•kg⁻¹). Another 10 sham-operated rats were set as control (S). Ten minutes after the administration, the cerebrospinal fluid was taken to test the content of catalpol and puerarin, and the brain tissue was taken to test the expression of β2-adrenergic receptor, eNOS, and NO. Compared with the M group, the ZG group showed content of catalpol is 26.673 μg•L⁻¹ and the content of puerarin is below the detection limit;the expression levels of β2-adrenergic receptor, eNOS and the contents of NO in brain tissue are no significant difference. Compared with the ZG group, the ZGB, ZB and GB groups showed significantly increased content of catalpol andpuerarin, as well as the expression of β2-adrenergic receptor, eNOS and NO in the brain tissue (P<0.05). The content of catalpol in BTX+ZG group changed non-significantly. Compared with the ZGB group, the BTX+ZGB group presented significantly decreased content of catalpol and puerarin and reduced expression of eNOS and NO in the brain tissue (P<0.05).The results demonstrated that borneol could dramatically promote catalpol and puerarin crossing through BBB in the focal cerebral ischemic rats. Moreover, the effect may be related to the up-regulation of β2-adrenergic receptor and the increasing expression of eNOS and NO.

Keywords: NO; blood-brain barrier; bornrol; catalpol; eNOS; puerarin; β2-adrenergic receptor.

MeSH terms

  • Animals
  • Blood-Brain Barrier*
  • Brain Ischemia / drug therapy*
  • Camphanes / pharmacology*
  • Iridoid Glucosides / pharmacology*
  • Isoflavones / pharmacology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Rats
  • Receptors, Adrenergic, beta-2 / metabolism

Substances

  • Camphanes
  • Iridoid Glucosides
  • Isoflavones
  • Receptors, Adrenergic, beta-2
  • catalpol
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • isoborneol
  • puerarin