Alpinia katsumadai H AYATA Seed Extract Inhibit LPS-Induced Inflammation by Induction of Heme Oxygenase-1 in RAW264.7 Ce
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Alpinia katsumadai HAYATA Seed Extract Inhibit LPS-Induced Inflammation by Induction of Heme Oxygenase-1 in RAW264.7 Cells Mee-Young Lee,1 Chang-Seob Seo,1 Jin-Ah Lee,1,2 In-Sik Shin,1 Su-Jeong Kim,1 HeyKyung Ha,1 and Hyeun-Kyoo Shin1,3
Abstract—In the present study, we investigated the effects of Alpinia katsumadai HAYATA (Zingiberaceae) seed ethanolic extract (AKEE) and its three components on the production of inflammatory mediators and some potential underlying mechanisms in lipopolysaccharide (LPS)-induced inflammation RAW264.7 cells. The whole formula, AKEE, and three major component compounds were then evaluated for their effects on inflammation-related parameters using LPS-induced RAW264.7 cells. Production of namely nitric oxide (NO) and cytokine levels were measured by the Griess reagent and ELISA, respectively. To investigate the underlying mechanisms of anti-inflammatory activities of AKEE, protein expression of nitric oxide synthase (inducible nitric oxide synthase, iNOS), heme oxygenase-1 (HO-1), and nuclear factor-kappa B (NF-κB) were evaluated by western blot analysis. AKEE and the major group of compounds in AKEE (alpinetin, cardamonin, and pinocembrin) complement exert anti-inflammatory effects for NO and PGE2 production. In addition, AKEE treatment significantly inhibited the LPS-induced production of interleukin-6 and tumor necrosis factor (TNF)-α, as well as the expression of iNOS. AKEE also induced HO-1 expression in RAW264.7 cells and inhibited the nuclear translocation of NF-κB by preventing degradation of the inhibitor kappa B-alpha. We also demonstrated that the effects of AKEE on TNF-α production were partially reversed by the HO-1 inhibitor tin protoporphyrin. These results indicate that AKEE and its major component may have anti-inflammatory activity via induction of HO-1 expression was partly responsible for the anti-inflammatory effects. KEY WORDS: Alpinia katsumadai HAYATA (Zingiberaceae); heme oxygenase; inflammation.
INTRODUCTION
they initiate many intracellular cascades of cytokines and chemokines [1]. Activated macrophages secrete a number of different inflammatory mediators, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, prostaglandin (PG)E2, and nitric oxide (NO) [2]. The latter, which is a potent pro-inflammatory mediator, is generated when inducible nitric oxide synthase (iNOS) stimulates the oxidative deamination of L-arginine [3]. Generally, the hydrophobic lipid region of LPS combines with Toll-like receptors and transducer signals to become intracellular signals. These signals can induce an inflammatory response that involves the activation of transcription factors such as nuclear factor-kappa B (NF-κB) and activating protein-1 [4]. NF-κB crucially mediates the production of IL-6, TNF-α, NO, PGE2, and other inflammatory mediators from activated
Inflammation is the normal physiological immune response to tissue injury or infection. During this process, macrophages and monocytes are activated by components of the invading pathogenic bacteria, and Mee-Young Lee and Chang-Se
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