Induced cortical neurogenesis after focal cerebral ischemia – Three active components from Huang-Lian-Jie-Du Decoction. (3rd February 2016)

• Record Type: Journal Article
• Authors: Zou, Haiyan; Long, Jianfei; Zhang, Qiuxia; Zhao, Haiyu; Bian, Baolin; Wang, Yali; Zhang, Jian; Zhao, Hui; Wang, Lei
• Is Part Of: Journal of ethnopharmacology. Volume 178(2016)
• Page Start: 115
• Page End: 124
• Publication Date: 2016-02-03
• Subjects: 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 densities -- SD standard deviation -- MAP-2 Microtubule-associated protein 2 -- GFAP Glial Fibrillary Acidic Protein -- PI3K Phosphatidylinositol 3-kinase -- AKT Protein kinase B -- GSK-3β Glycogen Synthase Kinase-3β -- GAPDH Glyceraldehyde-3-phosphate dehydrogenase; Baicalin (PubChem CID: 64982) -- Wogonoside (PubChem CID: 29927693) -- Baicalein (PubChem CID: 5281605) -- Wogonin (PubChem CID: 5281703) -- Gardenoside (PubChem CID: 442423) -- Genipin-gentiobiosid (PubChem CID: 3082301) -- Geniposide (PubChem CID: 107848) -- Coptisine (PubChem CID: 72322) -- Epiberberine (PubChem CID: 160876) -- Berberine (PubChem CID: 2353) -- Palmatine (PubChem CID: 19009); Huang-Lian-Jie-Du-Decoction -- Neurogenesis -- Middle cerebral artery occlusion -- Stroke -- Alkaloids -- Flavonoids -- Iridoids; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2015.12.001
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: 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. Graphical abstract: