Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system

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• 作者：Min-Soo Kim^a ; ^b ; Ji Hye Bang^a ; Jun Lee^a ; ^b ; Jung-Soo Han^c ; Tae Gon Baik^d ; Won Kyung Jeon^a ; ^b ; ^{wkjeon@kiom.re.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chronic cerebral hypoperfusion ; Choline acetyltransferase ; Ginkgo biloba ; Neuroinflammation ; Toll-like receptor
• 刊名：Phytomedicine
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：23
• 期：12
• 页码：1356-1364
• 全文大小：2838 K

文摘

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).

Purpose

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).

Methods

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 40 mg/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).

Results

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.

Conclusions

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.