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“Inflammation is an important process because INCB024360 supplier it is one of the natural defense mechanisms

caused by the release of inflammatory mediators [e.g., (nitric oxide) NO and prostaglandin (PG)E2], cytokines [e.g., tumor necrosis factor (TNF)-α], and chemokines [1] and [2]. This event requires the activation of inflammatory cells such as macrophages via the ligation of their surface receptors (e.g., Toll-like receptors) [3]. The activation of Toll-like receptors in macrophages by ligands derived from pathogens triggers various cellular signaling cascades to activate transcription factors including nuclear factor (NF)-κB (p50 and p65), activator protein (AP)-1 [c-Fos, c-Jun, and activating transcription factor (ATF)-2], and interferon regulatory transcription factor (IRF)-3 to trigger the new expression of inflammatory genes [4], [5] and [6]. Although PLX3397 nmr inflammation is a normal response, acutely, excessive induced, or chronically sustained inflammatory responses are known to cause serious diseases including cancer, stroke, and diabetes. Therefore, it must be stressed that normalization of upregulated inflammation is crucial in prevention of such diseases [7], [8] and [9]. Korean Red Ginseng (KRG, steamed root of Panax ginseng C.A. Meyer, Araliaceae) is a well-known herbal medicine

traditionally used in Korea [10]. It has been used for a long time without displaying any toxic properties, thus, developing some anti-inflammatory preparation Regorafenib in vivo with KRG could be considered beneficial. Unlike acid polysaccharides that are known as major components contributing to upregulation of the body’s immune responses [11], red ginseng saponin fractions enriched with protopanaxadiol (PPD)-type ginsenosides have been reported as strong anti-inflammatory preparations [12]. Some PPD-type ginsenosides such as ginsenoside (G)-Rb1, G-Rb2, and G-Rd display strong anti-inflammatory properties under various conditions [13]. This notion

led us to establish a hypothesis that PPD-type saponins could be used as an anti-inflammatory remedy. In this study, therefore, we investigated the anti-inflammatory activity and molecular mechanism of the protopanaxadiol saponin fraction (PPD-SF). PPD-SFs, prepared by previously established methods [14], from KRG with higher amounts of protopanaxadiol-type ginsenosides (G-Rb1, G-Rc, G-Re, and G-Rb2) were kindly supplied by the Korea Ginseng Cooperation (Daejeon, Korea). Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), phorbol 12-myristate 13-acetate (PMA), and lipopolysaccharide (LPS, Escherichia coli 0111:B4) were purchased from Sigma Chemical Co. (St. Louis, MO, USA). BX795 and SP600125 were obtained from Calbiochem (La Jolla, CA, USA). Luciferase constructs containing promoters with binding sites for NF-κB, AP-1, and IRF-3 were used, as reported previously [15]. RAW264.7 cells, a BALB/c-derived murine macrophage cell line (ATCC No.