title: Equol, a Dietary Daidzein Gut Metabolite Attenuates Microglial Activation and Potentiates Neuroprotection In Vitro.
abstract: Estrogen deficiency has been well characterized in inflammatory disorders including neuroinflammation. Daidzein, a dietary alternative phytoestrogen found in soy (Glycine max) as primary isoflavones, possess anti-inflammatory activity, but the effect of its active metabolite Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) has not been well established. In this study, we investigated the anti-neuroinflammatory and neuroprotective effect of Equol in vitro. To evaluate the potential effects of Equol, three major types of central nervous system (CNS) cells, including microglia (BV-2), astrocytes (C6), and neurons (N2a), were used. Effects of Equol on the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), Mitogen activated protein kinase (MAPK) signaling proteins, and apoptosis-related proteins were measured by western blot analysis. Equol inhibited the lipopolysaccharide (LPS)-induced TLR4 activation, MAPK activation, NF-kB-mediated transcription of inflammatory mediators, production of nitric oxide (NO), release of prostaglandin E2 (PGE-2), secretion of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), in Lipopolysaccharide (LPS)-activated murine microglia cells. Additionally, Equol protects neurons from neuroinflammatory injury mediated by LPS-activated microglia through downregulation of neuronal apoptosis, increased neurite outgrowth in N2a cell and neurotrophins like nerve growth factor (NGF) production through astrocytes further supporting its neuroprotective potential. These findings provide novel insight into the anti-neuroinflammatory effects of Equol on microglial cells, which may have clinical significance in cases of neurodegeneration.
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. subedilali@gmail.com.
authors.forename: Lalita
authors.initials: L
authors.lastname: Subedi
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. ehji@gachon.ac.kr.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Ji
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. dyshin@gachon.ac.kr.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department Oriental Medicine Resources, College of Environmental & Bioresources Sciences, Chonbuk National University, Jeonju City 54896, Korea. jongsik.jin@jbnu.ac.kr.
authors.forename: Jongsik
authors.initials: J
authors.lastname: Jin
authors.affiliation: National Institute of Biological Resources, Environmental Research Complex, 42 Hwangyeong-ro, Seo-gu, Incheon 22689, Korea. naasyeo@korea.kr.
authors.forename: Joo Hong
authors.initials: JH
authors.lastname: Yeo
authors.affiliation: College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. sunnykim@gachon.ac.kr.|Gachon Medical Research Institute, Gil Medical Center, Inchon 21565, Korea. sunnykim@gachon.ac.kr.|Gachon Institute of Pharmaceutical Science, Gachon University; #191 Hambakmoe-ro, Yeonsu-gu,   Incheon 21565, Korea. sunnykim@gachon.ac.kr.
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D060754:Equol / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000066829:Neuroprotection; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D060754:Equol; C004742:daidzein; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Equol;  apoptosis;  neuroinflammation;  neuroprotection;  phytoestrogen