Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling.

BACKGROUND: Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. METHODS: Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. RESULTS: Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. CONCLUSIONS: A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells.

1-Deoxynojirimycin inhibits metastasis of B16F10 melanoma cells by attenuating the activity and expression of matrix metalloproteinases-2 and -9 and altering cell surface glycosylation.

1-Deoxynojirimycin (1-DNJ), an iminosugar rich in mulberry, has been shown to possess antimetastatic potential. The antimetastatic mechanisms of 1-DNJ in melanoma B16F10 cells were studied, as were the antimetastatic activity (cell adhesion, migration, and invasion) of 1-DNJ, matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) mRNA, and flow cytometric analysis of cell surface in melanoma B16F10 cells. 1-DNJ significantly inhibited invasion, migration, and cell-matrix adhesion and markedly decreased MMP-2 and MMP-9 activity and mRNA expression. In contrast, 1-DNJ effectively enhanced the expression of TIMP-2 mRNA. In addition, 1-DNJ significantly decreased abnormal glycosylation and/or sialylation on B16F10 melanoma cell surface but increased the levels of α-mannose. Thus, the antimetastatic effects of 1-DNJ against B16F10 melanoma cells are likely associated with its attenuated activities and expression of MMP-2/9, enhancement of the TIMP-2 mRNA expression, and alterations of the cell surface-binding motif. These results suggest that 1-DNJ may be useful as an adjuvant of antimetastatic agents such as cisplatin.

Anti-angiogenic effects and mechanisms of polysaccharides from Antrodia cinnamomea with different molecular weights.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia cinnamomea is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers and liver diseases. AIM OF THE STUDY: This study aimed to investigate the immunomodulatory effect on angiogenesis of polysaccharides from mycelia of Antrodia cinnamomea (PMAC). MATERIALS AND METHODS: PMAC were extracted in boiling water, precipitated with 95% ethanol, and separated into four different molecular weights (<5, 5-30, 30-100, > 100 kDa). Tube formation and chorioallantoic membrane (CAM) assay were used to determine the in vitro and ex vivo anti-angiogenic effects. RESULTS: Only the PMAC-mononuclear cells (MNCs)-conditioned medium (CM) with MW > 100 kDa significantly and concentration-dependently decreased the secretion of vascular endothelial growth factor in human leukemia cells and inhibited the matrigel tube formation in human umbilical vein endothelial cells. Similarly only the PMAC-MNC-CM with MW > 100 kDa significantly and concentration-dependently increased the levels of interleukin (IL)-12 and interferon-gamma (IFN-gamma). In addition, the ex vivo CAM assay revealed that only the PMAC with MW>100 kDa significantly and dose-dependently inhibited neovascularization. CONCLUSIONS: PMAC with MW > 100 kDa are anti-angiogenic in vitro and ex vivo, and the effects are likely through immunomodulation.