PMID- 28588226 OWN - NLM STAT- MEDLINE DCOM- 20181218 LR - 20181218 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Jun 6 TI - The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity. PG - 2882 LID - 10.1038/s41598-017-03115-y [doi] LID - 2882 AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ALS-associated mutant copper-zinc superoxide dismutase (SOD1)-mediated toxicity. Ethanol extract of brazilian green propolis (EBGP) protected N2a cells against mutant SOD1-induced neurotoxicity and reduced aggregated mutant SOD1 by induction of autophagy. Kaempferide and kaempferol, the active ingredients of EBGP, also inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Both kaempferide and kaempferol significantly suppressed mutant SOD1-induced superoxide in mitochondria. Western blot analysis showed that kaempferol potentially induced autophagy via the AMP-activated protein kinase (AMPK) - the mammalian target of rapamycin (mTOR) pathway. These results suggest that EBGP containing the active ingredient against mutant SOD1-mediated toxicity is a promising medicine or health food for prevention and treatment of ALS. FAU - Ueda, Tomoyuki AU - Ueda T AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. FAU - Inden, Masatoshi AU - Inden M AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. FAU - Shirai, Katsuhiro AU - Shirai K AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. FAU - Sekine, Shin-Ichiro AU - Sekine SI AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. FAU - Masaki, Yuji AU - Masaki Y AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. FAU - Kurita, Hisaka AU - Kurita H AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. FAU - Ichihara, Kenji AU - Ichihara K AD - Nagaragawa Research Center, Api Company Limited, Gifu, Japan. FAU - Inuzuka, Takashi AU - Inuzuka T AD - Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Hozumi, Isao AU - Hozumi I AD - Lab. Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical Univ, Gifu, Japan. hozumi@gifu-pu.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170606 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antioxidants) RN - 0 (Flavonols) RN - 0 (Kaempferols) RN - 0 (Protective Agents) RN - 0 (Protein Aggregates) RN - 731P2LE49E (kaempferol) RN - 9009-62-5 (Propolis) RN - EC 1.15.1.1 (Superoxide Dismutase-1) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Antioxidants/chemistry/pharmacology MH - Autophagy MH - Flavonols/chemistry/*pharmacology MH - Kaempferols/pharmacology MH - Mice MH - Motor Neurons/drug effects/metabolism MH - *Mutation MH - Phosphorylation MH - Propolis/chemistry/*pharmacology MH - Protective Agents/chemistry/*pharmacology MH - Protein Aggregates MH - Superoxide Dismutase-1/*genetics/*metabolism PMC - PMC5460160 COIS- The authors declare that they have no competing interests. EDAT- 2017/06/08 06:00 MHDA- 2018/12/19 06:00 PMCR- 2017/06/06 CRDT- 2017/06/08 06:00 PHST- 2016/12/21 00:00 [received] PHST- 2017/04/24 00:00 [accepted] PHST- 2017/06/08 06:00 [entrez] PHST- 2017/06/08 06:00 [pubmed] PHST- 2018/12/19 06:00 [medline] PHST- 2017/06/06 00:00 [pmc-release] AID - 10.1038/s41598-017-03115-y [pii] AID - 3115 [pii] AID - 10.1038/s41598-017-03115-y [doi] PST - epublish SO - Sci Rep. 2017 Jun 6;7(1):2882. doi: 10.1038/s41598-017-03115-y.