title: Induced cortical neurogenesis after focal cerebral ischemia--Three active components from Huang-Lian-Jie-Du Decoction.
abstract: BACKGROUND
  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 2h 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.
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zou
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Long
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Bian
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China. Electronic address: zhaohuishouyi@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China. Electronic address: tmwangl@ccmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D039823:Iridoids; D018696:Neuroprotective Agents; C061676:oren gedoku to; D001973:Bromodeoxyuridine
keywords: Alkaloids; Baicalein (PubChem CID: 5281605); Baicalin (PubChem CID: 64982); Berberine (PubChem CID: 2353); Coptisine (PubChem CID: 72322); Epiberberine (PubChem CID: 160876); Flavonoids; Gardenoside (PubChem CID: 442423); Genipin-gentiobiosid (PubChem CID: 3082301); Geniposide (PubChem CID: 107848); Huang-Lian-Jie-Du-Decoction; Iridoids; Middle cerebral artery occlusion; Neurogenesis; Palmatine (PubChem CID: 19009); Stroke; Wogonin (PubChem CID: 5281703); Wogonoside (PubChem CID: 29927693)