Kim Min-Soo, Bang Ji Hye, Lee Jun, Han Jung-Soo, Baik Tae Gon, Jeon Won Kyung
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, The Republic of Korea.
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, The Republic of Korea.
Phytomedicine. 2016 Nov 15;23(12):1356-1364. doi: 10.1016/j.phymed.2016.07.013. Epub 2016 Aug 1.
Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH).
In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo).
Chronic BCCAo was induced in adult male Wistar rats to reflect the CCH conditions. On day 21 after BCCAo, the animals were treated orally with saline or GBE (5, 10, 20, and 40mg/kg) daily for 42 days. After the final treatment, brain tissues were isolated for the immunohistochemical analysis of glial markers and choline acetyltransferase (ChAT), as well as for the western blot analysis of proinflammatory cytokines, toll-like receptor (TLR)-related pathway, receptor for advanced glycation end products (RAGE), angiotensin-II (Ang-II), and phosphorylated mitogen-activated protein kinases (MAPKs).
BCCAo increased glial proliferation in the hippocampus and white matter, whereas proliferation was significantly attenuated by GBE treatment. GBE also attenuated the BCCAo-related increases in the hippocampal expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), TLR4, myeloid differentiation primary response gene 88, RAGE, Ang-II, and phosphorylated MAPKs (ERK, p38, and JNK). Furthermore, GBE treatment restored the ChAT expression in the basal forebrain following BCCAo.
These findings suggest that GBE has specific neuroprotective effects that may be useful for the treatment of CCH. The pharmacological mechanism of GBE partly involves the modulation of inflammatory mediators and the cholinergic system.
银杏叶提取物（GBE）是一种广泛使用的营养保健品，据报道具有多种功能，包括对记忆的积极作用和血管舒张特性。尽管众多研究评估了GBE在缺血中的神经保护特性，但仅有少数研究探讨了GBE在慢性脑灌注不足（CCH）中的神经药理作用机制。
在本研究中，我们试图确定GBE对双侧颈总动脉闭塞（BCCAo）大鼠模型中CCH诱导的神经炎症和胆碱能功能障碍的影响。
在成年雄性Wistar大鼠中诱导慢性BCCAo以反映CCH情况。在BCCAo后第21天，动物每天口服生理盐水或GBE（5、10、20和40mg/kg），持续42天。末次治疗后，分离脑组织用于胶质细胞标志物和胆碱乙酰转移酶（ChAT）的免疫组化分析，以及促炎细胞因子、Toll样受体（TLR）相关途径、晚期糖基化终末产物受体（RAGE）、血管紧张素-II（Ang-II）和磷酸化丝裂原活化蛋白激酶（MAPKs）的蛋白质印迹分析。
BCCAo增加了海马和白质中的胶质细胞增殖，而GBE治疗可显著减轻这种增殖。GBE还减轻了BCCAo相关的海马促炎细胞因子（TNF-α、IL-1β和IL-6）、TLR4、髓样分化初级反应基因88、RAGE、Ang-II和磷酸化MAPKs（ERK、p38和JNK）表达的增加。此外，GBE治疗恢复了BCCAo后基底前脑的ChAT表达。
这些发现表明GBE具有特定的神经保护作用，可能对CCH的治疗有用。GBE的药理机制部分涉及炎症介质和胆碱能系统的调节。
