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Canthin-6-one (CO) alkaloids possess various biological activities, including antibacterial, antitumor, antifungal, and antiviral activities. However, their anti-inflammatory effects and underlying molecular mechanisms are poorly characterized. This study aimed to investigate the anti-inflammatory effects of CO and its derivative 5-(1-hydroxyethyl)-canthin-6-one (5-HCO), isolated from the stem barks of Ailanthus altissima in lipopolysaccharide (LPS)-stimulated macrophages. CO (1 and 5 µM) and 5-HCO (7.5 and 15 µM) significantly inhibited the LPS-induced expression of inducible nitric oxide synthase. In addition, CO (1 and 5 µM) and 5-HCO (15 µM) markedly suppressed the production of prostaglandin E2 (PGE2) and expression of cyclooxygenase-2, a key enzyme in PGE2 synthesis, in LPS-stimulated macrophages. Moreover, CO treatment significantly reduced monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) expression, whereas 5-HCO inhibited MCP-1, but not TNF-α expression. Both CO and 5-HCO inhibited the phosphorylation of inhibitor kappa B and transcriptional activation of nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. In addition, CO, but not 5-HCO, markedly reduced Akt phosphorylation. Taken together, these data suggest that CO, but not 5-HCO with a hydroxyethyl moiety on the D ring, has potent anti-inflammatory activity in LPS-stimulated macrophages through the downregulation of both the NF-κB and the Akt pathway. [ABSTRACT FROM AUTHOR]

Panax ginseng has been reported to have cancerpreventive properties and, through anti-inflammatory, antioxidant, and pro-apoptotic mechanisms, to influence gene expression. However, the comparison of Korean white ginseng (WG) and red ginseng (RG) in their apoptotic effects and the identification of the selective cellular uptake of the ginsenosides in human breast cancer cells have not yet been fully understood. In the present study, the relative nonpolar and protopanaxadiol (PPD) class ginsenosides exhibited more cytotoxic and efficient cellular uptake on MCF-7 cells compared with the relative polar and protopanaxatriol (PPT) class compounds. PPD class ginsenosides were present in RG in a 2.5 times higher concentration as compared to WG, while PPT class ginsenosides were only present in WG. Thus, RG exerted more potent cytotoxicity than WG against MCF-7 and MDA-MB231 cells. RG also increased the sub-G1 DNA contents of the cell cycle and Annexin V-positive apoptotic bodies undergoing apoptosis through the caspase- 3 activation in MCF-7 cells. In addition, RG downregulated the proliferative and anti-apoptotic gene products and potentiated paclitaxelinduced apoptosis in MCF-7 cells. Overall, RG contained a higher concentration of PPD class ginsenosides as compared to WG; the greater cellular uptake of PPD resulted in more substantial antiproliferative activity in human breast cancer cells. [ABSTRACT FROM AUTHOR]