Inhibition of inducible nitric oxide synthase by Acanthopanax senticosus extract in RAW264.7 macrophages. 2008

Qiu-Ye Lin, and Li-Ji Jin, and Zhen-Hui Cao, and Yong-Ping Xu
Department of Bioscience and Biotechnology, Dalian University of Technology, 2 Linggong Road, Ganjingzi District, Dalian, Liaoning 116024, People's Republic of China.

OBJECTIVE The herb Acanthopanax senticosus (Siberian ginseng) has long been used as a traditional medicine. However, little is known about anti-inflammatory effects and its mechanisms of action. Excess production of nitric oxide (NO) is one of the characteristics of inflammation. In this study we examined the effects of A. senticosus extract (ASE) on NO production and inducible nitric oxide synthase (iNOS) gene expression in lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated RAW264.7 macrophages and investigated its mechanisms of anti-inflammatory activity. METHODS RAW264.7 macrophages were treated with 10 microg/ml LPS plus 20U/ml IFN-gamma in the presence or absence of ASE. NO production and iNOS gene expression were investigated. We further evaluated the effect of ASE on oxidative stress-sensitive transcription nuclear factor-kappa B (NF-kappaB) activation. RESULTS ASE significantly suppressed NO production and iNOS gene expression in a dose-dependent manner. ASE also reduced DNA-binding activity of NF-kappaB in LPS plus IFN-gamma stimulated RAW264.7 macrophages. Further studies indicated that LPS plus IFN-gamma-induced inhibitory factor-kappa B alpha (I-kappaBalpha) degradation and p65 nuclear translocation were inhibited in RAW264.7 macrophages exposed to ASE. Moreover, ASE inhibited the LPS plus IFN-gamma mediated increase in intracellular peroxides production. CONCLUSIONS These results suggest ASE suppresses iNOS gene expression through the inhibition of intracellular peroxides production, which has been implicated in the activation of NF-kappaB.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008516 Medicine, Chinese Traditional A system of traditional medicine which is based on the beliefs and practices of the Chinese culture. Chinese Medicine, Traditional,Chung I Hsueh,Traditional Medicine, Chinese,Zhong Yi Xue,Chinese Traditional Medicine,Traditional Chinese Medicine,Traditional Tongue Assessment,Traditional Tongue Diagnosis,Hsueh, Chung I,Tongue Assessment, Traditional,Tongue Diagnoses, Traditional,Tongue Diagnosis, Traditional,Traditional Tongue Assessments,Traditional Tongue Diagnoses
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010545 Peroxides A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed) Peroxide
D010936 Plant Extracts Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard. Herbal Medicines,Plant Extract,Extract, Plant,Extracts, Plant,Medicines, Herbal
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response

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