title: KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells.
abstract: The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)-1 and to determine their mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO-1 in lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B-α (IκB-α) phosphorylation and degradation and nuclear factor kappa B (NF-κB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1 expression by promoting nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory mediators and proteins associated with HO-1 expression. Our data suggest that KCHO-1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation.
authors.affiliation: Inha Research Institute for Medical Sciences, Department of Biochemistry, Inha University School of Medicine, Incheon 400-712, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Chi-Su
authors.initials: CS
authors.lastname: Yoon
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Dong-Cheol
authors.initials: DC
authors.lastname: Kim
authors.affiliation: Hanpoong Pharm & Foods Co., Ltd., Jeonju, 561-841, Republic of Korea.
authors.forename: Jinju
authors.initials: J
authors.lastname: Yun
authors.affiliation: Hanpoong Pharm & Foods Co., Ltd., Jeonju, 561-841, Republic of Korea.
authors.forename: Jun-Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Hanpoong Pharm & Foods Co., Ltd., Jeonju, 561-841, Republic of Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Jun
authors.affiliation: Department of Neurology, Inam Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Ilhong
authors.initials: I
authors.lastname: Son
authors.affiliation: Department of Internal Medicine, Wonkwang University College of Korean Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Dong-Woung
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Oriental Internal Medicine, Wonkwang Gwangju Oriental Medical Hospital, 543-8 Juwol Dong, Nam-gu, Gwangju 503-310, Republic of Korea.
authors.forename: Bong-Keun
authors.initials: BK
authors.lastname: Song
authors.affiliation: Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Seulah
authors.initials: S
authors.lastname: Choi
authors.affiliation: Inha Research Institute for Medical Sciences, Department of Biochemistry, Inha University School of Medicine, Incheon 400-712, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.affiliation: ALS/MND Center of Wonkwang University Korean Medical Hospital, 543-8 Juwol Dong, Nam-gu, Gwangju 503-310, Republic of Korea.
authors.forename: Sungchul
authors.initials: S
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim