title: BJ-1103, 6-aminopyridin-3-ol skeletal compound, modulates neuroprotective and anti-neuroinflammatory effects in murine hippocampal and microglial cells via Nrf2-mediated heme oxygenase-1 expression.
abstract: BJ-1103, as a 6-aminopyridin-3-ol skeletal compound, was originally developed as an antioxidant against free radicals and oxidative stress was prepared from pyridoxine·HCl by the reported procedure. In the present study, we examined the effect of BJ-1103 on neuroprotection and neuroinflammation. Our data showed that BJ-1103 can protect HT22 cells against glutamate-induced cell cytotoxicity. And, BJ-1103 also inhibited LPS-induced inflammatory action. In addition, BJ-1103-induced heme oxygenase-1 (HO-1) expression and elevated HO-1 activities in the two cell lines studied. Additionally, BJ-1103 treatment induced nuclear transcription factor erythroid-2 related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs). We have demonstrated using the Nrf2 siRNA, HO inhibitor or HO-1 siRNA that BJ-1103 suppressed neurotoxicity and neuroinflammation through the Nrf2-mediated HO-1 expression. These results demonstrated that BJ-1103 may have good therapeutic agent against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Chosun University, Dong-gu, Gwangju, 61452, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Republic of Korea.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address: jeongb@ynu.ac.kr.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea. Electronic address: gsjeong@kmu.ac.kr.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
keywords: 6-Aminopyridin-3-ol skeletal BJ-1103; Heme oxygenase-1; Hippocampal HT22; Microglial BV2; Nuclear transcription factor erythroid-2 related factor 2