Wang Hong-Jin, Wu Jun-Jie, Xue Qiang, Zhang Ji-Fen, Xu Xiao-Yu
Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Pharmacology of Chinese Materia Medica-the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine, College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing 400715, China.
College of Pharmacy & College of Traditional Chinese Medicine, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.
Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(11):2200-2207. doi: 10.19540/j.cnki.cjcmm.2017.0100.
In recent twenty years, there are a lot of studies about the effect of borneol on permeability of blood-brain barrier(BBB); however, it isDODOrt of regular conclusions of effect factors and in-depth analysis of functional mechanisms. The current researching data were collected and analyzed in this paper for illuminating the effect factors and mechanisms of borneol on permeability of BBB.The following conclusions were obtained: five factors about borneol influencing the permeability of BBB. First, opticity activity of borneol had no significant effect on action effects. Second, dose of borneol in the range of 50.00-200.00 mg•kg⁻¹, did not affect the effect direction, but only affect its action intensity either with use alone or combination use. Third, the borneol can increase the permeability of physiological BBB, and decrease the permeability of pathological BBB. Fourth, regardless of using singly or using compatibility with musk, borneol can decrease the permeability of BBB in different brain disease models. Fifth, when used with astragalus, catalpol or puerarin, borneol can increase the permeability of BBB and promote the drugs through BBB in pathological conditions. The target spots and mechanisms of borneol's bidirectional regulation on the permeability of BBB are related to the structure and function of cerebral endothelial cells, the exocytosis effects of P-gp and low pinocytosis internal transport effects. On one hand，borneol can down-regulate P-gp by inhibiting NF-κB to reduce the exocytosis effects of P-gp and promote the blood brain barrier pinocytosis to increase the permeability of BBB; On the other hand，borneol can reduce the degradation of basement membrane of blood vessel and tight junctions by inhibiting the expression of IL-1β, MMP-9 to decrease the permeability of BBB；moreover，borneol has bidirectional regulation effects on blood-brain barrier permeability by influencing the signaling pathways of Ca2+-eNOS-NO, VEGF-eNOS-NO. However, the detailed mechanisms that borneol regulates and controls the permeability of BBB are so complicated, so they shall be further proved and clarified.
近二十年来，有许多关于冰片对血脑屏障（BBB）通透性影响的研究；然而，对于影响因素的规律性结论及功能机制的深入分析尚显不足。本文收集并分析了当前的研究数据，以阐明冰片对血脑屏障通透性的影响因素及机制。得出以下结论：冰片影响血脑屏障通透性的五个因素。其一，冰片的旋光活性对作用效果无显著影响。其二，冰片剂量在50.00 - 200.00 mg•kg⁻¹范围内，无论单独使用还是联合使用，均不影响作用方向，仅影响其作用强度。其三，冰片可增加生理性血脑屏障的通透性，降低病理性血脑屏障的通透性。其四，无论单独使用还是与麝香配伍使用，冰片均可降低不同脑疾病模型中血脑屏障的通透性。其五，与黄芪、梓醇或葛根配伍使用时，冰片可增加病理性条件下血脑屏障的通透性并促进药物透过血脑屏障。冰片对血脑屏障通透性双向调节的靶点及机制与脑内皮细胞的结构和功能、P - gp的胞吐作用及低胞饮内转运作用有关。一方面，冰片可通过抑制NF - κB下调P - gp，减少P - gp的胞吐作用并促进血脑屏障胞饮作用以增加血脑屏障的通透性；另一方面，冰片可通过抑制IL - 1β、MMP - 9的表达减少血管基底膜和紧密连接的降解以降低血脑屏障的通透性；此外，冰片通过影响Ca2⁺ - eNOS - NO、VEGF - eNOS - NO信号通路对血脑屏障通透性具有双向调节作用。然而，冰片调控血脑屏障通透性的详细机制十分复杂，有待进一步证实和阐明。
