Induced cortical neurogenesis after focal cerebral ischemia - Three active components from Huang-Lian-Jie-Du Decoction

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• 作者：Haiyan Zou^a ; ^b ; ¹ ; Jianfei Long^a ; ^b ; ^d ; ¹ ; Qiuxia Zhang^a ; ^b ; Haiyu Zhao^c ; Baolin Bian^c ; Yali Wang^a ; ^b ; Jian Zhang^a ; ^b ; Hui Zhao^a ; ^b ; ^{zhaohuishouyi@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Lei Wang^a ; ^b ; ^{tmwangl@ccmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HLJDD ; Huang-Lian-Jie-Du-Decoction ; BrdU ; 5-bromodeoxyuridine ; TCM ; Traditional Chinese Medicine ; pMACO ; permanent middle cerebral artery occlusion ; CNS ; Central Nervous System ; VEGF ; Vascular Endothelial Growth Factor ; Ang ; Angiopoietin ; qRT-PCR ; quantitative real time-polymerase chain reaction ; CCA ; common carotid artery ; ECA ; external carotid artery ; ICA ; internal carotid artery ; BCA ; bicinchoninic acid ; PAGE ; polyacrylamide gel electrophoresis ; PVDF ; polyvinylidene fluoride ; ODs ; Optical den
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：3 February 2016
• 年：2016
• 卷：178
• 期：Complete
• 页码：115-124
• 全文大小：6285 K

文摘

Huang-Lian-Jie-Du-Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) clinical prescription noted for its neuroprotective effects. The total alkaloids, flavonoids, and iridoids are the main active components of HLJDD. In the present study we explored the possible effects of the total alkaloids, flavonoids, and iridoids from HLJDD on behavioral recovery and cortical neurogenesis after stroke.

Methods

The stroke model was induced by permanent middle cerebral artery occlusion (pMACO). The total alkaloids (44 mg/kg), flavonoids (50 mg/kg), and iridoids (80 mg/kg) from HLJDD were orally administered for 2 h after stroke and daily thereafter. Neurological function was assessed and then rats were sacrificed 7 days after pMACO. Following repeated intraperitoneal injections of the cell proliferation – specific marker 5-bromodeoxyuridine (BrdU) after stroke induction, precursor cell proliferation and differentiation was monitored by immunofluorescent staining. The levels of relevant proteins were determined by western blotting and the mRNA expressions were assessed by quantitative real time-polymerase chain reaction (qRT-PCR).

Results

Total alkaloids, flavonoids and iridoids from HLJDD showed improved functional outcome after brain ischemia. The total alkaloids and iridoids increased number of BrdU-positive cells and enhanced neuronal differentiation in the cortex. Alkaloids-enhanced neurogenesis might be associated with increased VEGF, Ang-1, and Ang-2 protein expression. And the neuroproliferative effect of alkaloids was partially correlated with increased phosphorylation of AKT, and GSK-3β. Flavonoids treatment was found to promote differentiation of cortical precursor cells into neuronal but not glial cells, which may be at least attributable to the regulation of AKT, GSK-3β mRNA and Ang-1 protein levels.

Conclusions

Total alkaloids, iridoids and flavonoids from HLJDD promoted functional recovery likely via enhancing cortical neurogenesis and thus have potential as a treatment for ischemic brain injury.