Wu Jun-Jie, Wang Hong-Jin, Yang Shuai, Liu Yang, Xu Xiao-Yu
College of Pharmaceutical Sciences & College of Chinese Medicine, Institute of Chinese Medicine, Southwest University, Chongqing Engineering Research Center for Pharmacodynamics Evaluation, Chongqing 400715, China.
Zhongguo Zhong Yao Za Zhi. 2016 Nov;41(21):3988-3995. doi: 10.4268/cjcmm20162117.
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.
以往研究表明,冰片在一定条件下可促进某些药物透过血脑屏障(BBB)。然而,其机制尚未阐明。本研究旨在探讨冰片对梓醇和葛根素透过血脑屏障的促进作用,并探索相关机制。将局灶性脑缺血大鼠随机分为7组,然后给予相应药物:模型组(M,溶剂)、梓醇 - 葛根素组(ZG,梓醇45 mg•kg⁻¹ + 葛根素200 mg•kg⁻¹)、梓醇 - 葛根素 - 冰片组(ZGB,梓醇45 mg•kg⁻¹ + 葛根素200 mg•kg⁻¹ + 冰片200 mg•kg⁻¹)、梓醇 - 冰片组(ZB,梓醇45 mg•kg⁻¹ + 冰片200 mg•kg⁻¹)、葛根素 - 冰片组(GB,葛根素200 mg•kg⁻¹ + 冰片200 mg•kg⁻¹)、布托沙明 - ZG组(BTX + ZG,布托沙明1.5 mg•kg⁻¹ + 梓醇45 mg•kg⁻¹ + 葛根素200 mg•kg⁻¹)、布托沙明 - ZGB组(BTX + ZGB,布托沙明1.5 mg•kg⁻¹ + 梓醇45 mg•kg⁻¹ + 葛根素200 mg•kg⁻¹ + 冰片200 mg•kg⁻¹)。另设10只假手术大鼠作为对照(S)。给药10分钟后,采集脑脊液检测梓醇和葛根素含量,取脑组织检测β2 - 肾上腺素能受体、内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)的表达。与M组相比,ZG组梓醇含量为26.673 μg•L⁻¹,葛根素含量低于检测限;脑组织中β2 - 肾上腺素能受体、eNOS的表达水平及NO含量无显著差异。与ZG组相比,ZGB、ZB和GB组梓醇和葛根素含量显著增加,脑组织中β2 - 肾上腺素能受体、eNOS的表达及NO含量也显著增加(P<0.05)。BTX + ZG组梓醇含量变化不显著。与ZGB组相比,BTX + ZGB组梓醇和葛根素含量显著降低,脑组织中eNOS和NO的表达减少(P<0.05)。结果表明,冰片可显著促进局灶性脑缺血大鼠中梓醇和葛根素透过血脑屏障。此外,其作用可能与β2 - 肾上腺素能受体上调以及eNOS和NO表达增加有关。