title: Inhibitory effect of a 2,4-bis(4-hydroxyphenyl)-2-butenal diacetate on neuro-inflammatory reactions via inhibition of STAT1 and STAT3 activation in cultured astrocytes and microglial BV-2 cells.
abstract: 2,4-Bis(p-hydroxyphenyl)-2-butenal (Butenal), a tyrosine-fructose Maillard reaction product has been demonstrated as an effective compound for prevention of neuroinflammatory diseases. However, this compound was vulnerable to environmental factors. Our research has been continuously made to improve druggability of Butenal and identified 2,4-bis(4-hydroxyphenyl)but-2-enal diacetate (HPBD) as an alternative. Herein, to investigate potential anti-neuroinflammatory and anti-amyloidogenic effects of HPBD, we treated HPBD (0.5, 1, and 2 μg/ml) on the lipopolysaccharides (LPS) (1 μg/ml) stimulated astrocytes and microglial BV-2 cell. HPBD inhibited LPS-induced NO and ROS production, and LPS-elevated expression of iNOS, COX2, β-site APP-cleaving enzyme 1 (BACE1), C99, and Aβ1-42 levels as well as attenuation of β-secretase activities. The activation of nuclear factor-kappaB (NF-κB), signal transducer and activator of transcription1 (STAT1), and STAT3 was concomitantly inhibited by HPBD. Moreover, siRNA targeting STAT3 abolished HPBD-induced inhibitory effects on neuro-inflammation and amyloidogenesis. In addition, pull down assay and docking model showed interaction of HPBD with STAT3. These findings suggest that HPBD may be useful and potentially therapeutic choices for the treatment of neuroinflammatory diseases.
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Hee Pom
authors.initials: HP
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Jin Yi
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Venkatareddy
authors.initials: V
authors.lastname: Udumula
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Dong Cheul
authors.initials: DC
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Chemistry, Utah Valley University, 800 W. University Parkway, Orem, UT 84058, USA.
authors.forename: Young Wan
authors.initials: YW
authors.lastname: Ham
authors.affiliation: College of Agriculture, Life and Environments Sciences, Chungbuk National University, 12 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Heon-Sang
authors.initials: HS
authors.lastname: Jung
authors.affiliation: College of Oriental Medicine, Kyungwon University, San 65 Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii 461-701, Republic of Korea. Electronic address: hssong70@gachon.ac.kr.
authors.forename: Ho Sueb
authors.initials: HS
authors.lastname: Song
authors.affiliation: College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea. Electronic address: jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000447:Aldehydes / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C000593234:2,4-bis(4-hydroxyphenyl)but-2-enal diacetate; D000085:Acetates; D000447:Aldehydes; D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D051550:I-kappa B Kinase
keywords: 2,4-Bis(4-hydroxyphenyl)but-2-enal diacetate; Anti-amyloidogenesis; Anti-neuroinflammation; NF-κB; STAT1; STAT3