title: Purification of kavalactones from Alpinia zerumbet and their protective actions against hydrogen peroxide-induced cytotoxicity in PC12 cells.
abstract: This study found that fruit shells of shell ginger (Alpinia zerumbet) are a rich source of the kavalactones dihydro-5,6-dehydrokavain (DDK) and 5,6-dehydrokavain (DK). The fruit shell extraction with hexane resulted in good purity and higher yields of DDK and DK than did chloroform, ethanol, 10% ethanol, methanol or water. Additionally, this study examined the neuroprotective effects of DDK and DK against H2O2-induced cytotoxicity in PC12 cells and the possible molecular mechanisms involved. 16 h after stimulation with 400 μM H2O2, the viability (MTT reduction) of PC12 cells decreased while membrane damage (LDH release) was noticeably increased. However, pretreatment for 6 h with DDK and DK (1 μM, 5 μM, 10 μM and 50 μM) rescued PC12 cells from H2O2-induced cytotoxicity, as evidenced by decreased LDH release and increased cell viability. DDK and DK inhibit the MAPK family member p38, activate AKT, and reduce caspase-3 activity. DDK also reduced the oxidative status in H2O2-treated PC12 cells. Together, our data indicate that the A. zerumbet constituents, DDK and DK, exert a protective effect against oxidative stress-induced PC12 cell death and that the regulation of p-Akt and the p38 MAPK, and of oxidative states may be involved.
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Yerra Koteswara
authors.initials: YK
authors.lastname: Rao
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Hui-Nung
authors.initials: HN
authors.lastname: Shih
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Cheng
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Hui-Chin
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Huang-Chi
authors.initials: HC
authors.lastname: Wang
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ching Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC.
authors.forename: Yew-Min
authors.initials: YM
authors.lastname: Tzeng
authors.affiliation: Department of Applied Biochemistry, Chaoyang University of Technology, 168 Gifeng East Road, Wufeng, Taichung 41349, Taiwan, ROC; Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: mjlee@cyut.edu.tw.
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000302:isolation & purification* / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000378:metabolism; D011753:Pyrones / Q000302:isolation & purification* / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011753:Pyrones; C000597693:dihydro-5,6-dehydrokavain; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C000597694:5,6-dehydrokavain
keywords: 5,6-Dehydrokavain; Alpinia zerumbet; Dihydro-5,6-dehydrokavain; Neuroprotection; Oxidative stress; PC12 cells