Search

The isolation of previously undescribed 12 compounds from the MeOH extract of Jacobaea vulgaris whole plants is disclosed, comprising 11 dihydrostilbenes (1 – 11) and one flavanone (12), and eight known compounds (six flavonoids, one dihydrostilbene, and one caffeoylquinic acid). Structural elucidation employed spectroscopic methods, including 1D and 2D NMR spectroscopy, HRESIMS, and ECD calculations. Evaluation of the compounds' effects on PCSK9 and LDLR mRNA expression revealed that compounds 1 and 3 downregulated PCSK9 mRNA while increasing LDLR mRNA expression, suggesting potential cholesterol-lowering properties. [Display omitted] • Undescribed dihydrostilbenes and flavanone were isolated from Jacobaea vulgaris. • Compounds without cytotoxicity were evaluated for their effects against PCSK9 expression. • Compounds 1 and 3 downregulated PCSK9 expression in mRNA level, implying the potentials of lowering cholesterol. [ABSTRACT FROM AUTHOR]

Resolution of inflammation is important for physiological homeostasis. Chronic inflammatory diseases may be caused by abnormal resolution of inflammation. However, what causes a failure of inflammatory resolution is unclear. Here we investigated the involvement of high mobility group box 1 (HMGB1) protein in the control of inflammatory resolution as an ‘anti-resolution factor’. We first confirmed the increased expression of HMGB1 and prostaglandin reductase 1 (PTGR1) in inflammatory conditions and HMGB1-mediated regulation of the expression of PTGR1. The inhibition of phagocytosis by HMGB1 was abrogated by PTGR1 silencing. PTGR1 was a direct target of miR522-3p and its expression was regulated by miRNA-522-3p inhibitor or mimic. Finally, miR-522-3p had an important role in the regulation of PTGR1 expression by HMGB1. The data indicates that HMGB1-miR-522-3p-PTGR1 axis may be involved in the abnormal resolution of inflammation and suggests that this mechanism might be a target for modulation of chronic inflammatory disorder. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Alpinia katsumadai was recently found in our previous study to have anti-migratory and anti-invasion activities against HT-1080 cells. However, the study did not demonstrate the exact component of Alpinia katsumadai with anti-migratory and anti-invasive activities. We tested the effects and relevant mechanism of cardamonin (CDN) on the migration and invasion of cancer cells. Main methods: Migration and invasion of cancer cells were measured using multi-well chambers. Zymography and Western blots were used to examine the effects of CDN on the activities of matrix metalloproteinases (MMPs) and expression of transglutaminase-2 (Tgase-2). Key findings: CDN, but not alpinetin, dose-dependently suppressed the migration and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion of HT-1080 sarcoma cells. CDN suppressed the expression of Tgase-2, MMP-2, NF-κB and MMP-9 in HT-1080 cells, and suppressed MMP-2 and MMP-9 activities. Gene silencing of Tgase-2 suppressed the migration and invasion of HT-1080 cells and suppressed the activities of MMP-2 and MMP-9. Migration of various cancer cells having high levels of Tgase-2 were also inhibited by CDN. CDN and Alpinia katsumadai extracts also directly inhibited the activity of Tgase-2. Significance: CDN inhibits migration of several cancer cell lines expressing Tgase-2 via suppression of Tgase-2 expression and inhibition of Tgase-2 activity. The finding that CDN has Tgase-2 inhibitory activity will give us a new scaffold or clue of pharmacophore for the development of more effective Tgase-2 inhibitors. [Copyright &y& Elsevier]

Abstract: Vitiligo is a progressive depigmenting disorder. Histamine has been shown to induce melanogenesis via histamine receptor 2, suggesting the possibility of histamine as a repigmenting agent for the treatment of vitiligo. However, the role and signaling mechanism of histamine are still unclear in melanogenesis, especially in relation to growth-differentiation factor-15, which is a protein belonging to transforming growth factor beta and found to be overexpressed in metastatic or malignant melanoma. We found that histamine induces growth-differentiation factor-15 in melanoma cell lines such as SK-MEL-2, B16F10, and melan-a cells. Therefore, in the present study, the role of growth-differentiation factor-15 in histamine-induced melanogenesis was investigated using gene silencing or overexpression of growth-differentiation factor-15 and histamine related compounds such as histamine, amthamine, and cimetidine. Gene silencing of growth-differentiation factor-15 suppressed histamine-induced proliferation, melanin production, tyrosinase activity, and chemotactic migration of SK-MEL-2 cells. Histamine-induced expression of tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 was also suppressed by growth-differentiation factor-15 gene silencing. On the other hand, overexpression of growth-differentiation factor-15 using a plasmid containing growth-differentiation factor-15 in SK-MEL-2 cells increased melanin production and chemotactic migration. Amthamine induced expression of growth-differentiation factor-15 in a time and concentration dependent manner. Amthamine-induced expression of growth-differentiation factor-15 was suppressed by cimetidine. Our results suggest that growth-differentiation factor-15 is a new player in histamine-induced melanogenesis, which can help researchers to extend the knowledge of the role of the transforming growth factor beta family in melanogenesis and in skin pigment disorders such as vitiligo. [Copyright &y& Elsevier]