title: AP-1/IRF-3 Targeted Anti-Inflammatory Activity of Andrographolide Isolated from Andrographis paniculata.
abstract: Andrographolide (AG) is an abundant component of plants of the genus Andrographis and has a number of beneficial properties including neuroprotective, anticancer, anti-inflammatory, and antidiabetic effects. Despite numerous pharmacological studies, the precise mechanism of AG is still ambiguous. Thus, in the present study, we investigated the molecular mechanisms of AG and its target proteins as they pertain to anti-inflammatory responses. AG suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the mRNA abundance of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF- α ), cyclooxygenase (COX)-2, and interferon-beta (IFN- β ) in a dose-dependent manner in both lipopolysaccharide- (LPS-) activated RAW264.7 cells and peritoneal macrophages. AG also substantially ameliorated the symptoms of LPS-induced hepatitis and EtOH/HCl-induced gastritis in mice. Based on the results of luciferase reporter gene assays, kinase assays, and measurement of nuclear levels of transcription factors, the anti-inflammatory effects of AG were found to be clearly mediated by inhibition of both (1) extracellular signal-regulated kinase (ERK)/activator protein (AP)-1 and (2) I κ B kinase ε (IKK ε )/interferon regulatory factor (IRF)-3 pathways. In conclusion, we detected a novel molecular signaling pathway by which AG can suppress inflammatory responses. Thus, AG is a promising anti-inflammatory drug with two pharmacological targets.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Yi
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Sung
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Kyung-Woon
authors.initials: KW
authors.lastname: Kim
authors.forename: Jong Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho