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      Anti-inflammatory function of arctiin by inhibiting COX-2 expression via NF-κB pathways

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          Abstract

          Background

          Arctiin, isolated from Forsythia suspensa has been reported to have anti-inflammatory, anti-oxidant, antibacterial, and antiviral effects in vitro. However, there has been a lack of studies regarding its effects on immunological activity. The aim of this study is to investigate the anti-inflammatory potential and possible mechanisms of arctiin in LPS-induced macrophages.

          Methods

          We investigated the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecule changes.

          Results

          Arctiin dose dependently decreased the production of NO and proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE 2, and it reduced the gene and protein levels as determined by RT-PCR and western blot analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 were also inhibited by arctiin. Furthermore, the activation of the nuclear transcription factor, NF-κB in macrophages was inhibited by arctiin.

          Conclusion

          Taken together these results provide evidence of the bioactivity of arctiin in inflammatory diseases and suggest that arctiin may exert anti-inflammatory effect by inhibiting the pro-inflammatory mediators through the inactivation of NF-kB.

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          Most cited references33

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          Cyclooxygenases 1 and 2.

          Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
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            Nitric oxide as a secretory product of mammalian cells.

            C. Nathan (1992)
            Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.
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              Altered immune responses in mice lacking inducible nitric oxide synthase.

              Nitric oxide (NO) is important in many biological functions. It is generated from L-arginine by the enzyme NO synthase (NOS). The cytokine-inducible NOS (iNOS) is activated by several immunological stimuli, leading to the production of large quantities of NO which can be cytotoxic. To define the biological role of iNOS further, we generated iNOS mutant mice. These are viable, fertile and without evident histopathological abnormalities. However, in contrast to wild-type and heterozygous mice, which are highly resistant to the protozoa parasite Leishmania major infection, mutant mice are uniformly susceptible. The infected mutant mice developed a significantly stronger Th1 type of immune response than the wild-type or heterozygous mice. The mutant mice showed reduced nonspecific inflammatory response to carrageenin, and were resistant to lipopolysaccharide-induced mortality.
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                Author and article information

                Journal
                J Inflamm (Lond)
                Journal of Inflammation (London, England)
                BioMed Central
                1476-9255
                2011
                7 July 2011
                : 8
                : 16
                Affiliations
                [1 ]College of Pharmacy, SahmYook University, Seoul 139-742, Republic of Korea
                [2 ]School of Life Sciences, Handong Global University, Pohang 791-708, Republic of Korea
                [3 ]College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea
                Article
                1476-9255-8-16
                10.1186/1476-9255-8-16
                3146809
                21733191
                05b89ca4-905b-4a9a-8643-5a47fd4eab7e
                Copyright ©2011 Lee et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 June 2010
                : 7 July 2011
                Categories
                Research

                Immunology
                Immunology

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