title: Emodin from Polygonum multiflorum ameliorates oxidative toxicity in HT22 cells and deficits in photothrombotic ischemia.
abstract: BACKGROUND
  Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. Emodin, an active component from Polygonum multiflorum Thunb., provides benefits for brain disturbances induced by severe cerebral injury.
  
  
  OBJECTIVE
  We investigated the neuroprotective effect of emodin from Polygonum multiflorum Thunb. against glutamate-induced oxidative toxicity and cerebral ischemia.
  
  
  METHODS
  For examination of neuroprotective effects of emodin, cell viability, cytotoxicity, flow cytometry, and Western blot were performed in HT22 cells and infarct volume, behavioral tests and Western blot in a mouse model of photothrombotic ischemic stroke.
  
  
  RESULTS
  Pretreatment with emodin resulted in significantly reduced glutamate-induced apoptotic cell death in HT22 cells. However, blocking of phosphatidylinositol-3 kinase (PI3K) activity with LY294002 resulted in significantly inhibited cell survival by emodin. Exposure of glutamate-treated cells to emodin induced an increase in the level of Bcl-2 expression, whereas the expression of Bax and active caspase-3 proteins was significantly reduced. In addition, treatment with emodin resulted in increased phosphorylation of Akt and cAMP response element binding protein (CREB), and expression of mature brain-derived neurotrophic factor (BDNF). This expression by emodin was also significantly inhibited by blocking of PI3K activity. In a photothrombotic ischemic stroke model, treatment with emodin resulted in significantly reduced infarct volume and improved motor function. We confirmed the critical role of the expression levels of Bcl-2/Bax, active caspase-3, phosphorylated (p)Akt, p-CREB, and mature BDNF for potent neuroprotective effects of emodin in cerebral ischemia.
  
  
  CONCLUSIONS
  These results suggest that emodin may afford a significant neuroprotective effect against glutamate-induced apoptosis through activation of the PI3K/Akt signaling pathway, and subsequently enhance behavioral function in cerebral ischemia.
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Department of Horticultural Bioscience, College of Natural Resource and Life Science, Pusan National University, Miryang 50463, Republic of Korea.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Department of Biochemistry, College of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea; Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Research Center for Anti-aging Technology Development, Pusan National University, Busan 46241, Republic of Korea; Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Republic of Korea; Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: choibt@pusan.ac.kr.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000302:isolation & purification / Q000494:pharmacology*; D000068676:Fallopia multiflora / Q000737:chemistry*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020767:Intracranial Thrombosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012395:Rose Bengal; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012395:Rose Bengal; D018698:Glutamic Acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D004642:Emodin
keywords: Emodin; Ischemia; Neuroprotection; Oxidative toxicity; Polygonum multiflorum