KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in Mouse BV2 Microglia Cells. (11th December 2014)

• Record Type: Journal Article
• Authors: Lee, Dong-Sung; Ko, Wonmin; Yoon, Chi-Su; Kim, Dong-Cheol; Yun, Jinju; Lee, Jun-Kyung; Jun, Ki-Young; Son, Ilhong; Kim, Dong-Woung; Song, Bong-Keun; Choi, Seulah; Jang, Jun-Hyeog; Oh, Hyuncheol; Kim, Sungchul; Kim, Youn-Chul
• Other Names: Leung Ping-Chung Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2014(2014)
• Publication Date: 2014-12-11
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2014/357154
• Languages: English
• ISSNs: 1741-427X

Abstract

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-1 β (IL-1 β ), and IL-6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B- α (I κ B- α ) phosphorylation and degradation and nuclear factor kappa B (NF- κ B) 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.