The roots/rhizomes of Cimicifuga racemosa L. (Nutt.) (black cohosh) have traditionally been used to treat menopausal symptoms through an unknown mechanism of action. In an effort to determine if black cohosh had additional health benefits, methanol extracts were investigated for their potential to scavenge reactive oxygen species and to protect against menadione-induced DNA damage. These extracts effectively scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. In addition, the extracts showed dose-dependent decreases in DNA single-strand breaks and oxidized bases induced by the quinone menadione using the comet (single-cell gel electrophoresis assay) and fragment length associated repair enzyme assays, respectively. Bioassay-directed fractionation of the methanolic extracts using the DPPH assay as a monitor led to the isolation of nine antioxidant active compounds: caffeic acid (1), methyl caffeate (2), ferulic acid (3), isoferulic acid (4), fukinolic acid (5), cimicifugic acid A (6), cimicifugic acid B (7), cimicifugic acid F (8), cimiracemate A (9), and cimiracemate B (10). Six of these antioxidants were found to reduce menadione-induced DNA damage in cultured S30 breast cancer cells with the following order of potency: methyl caffeate (2) > caffeic acid (1) > ferulic acid (3) > cimiracemate A (9) > cimiracemate B (10) > fukinolic acid (5). These data suggest that black cohosh can protect against cellular DNA damage caused by reactive oxygen species by acting as antioxidants.

Eight new and 13 known triterpene glycosides, along with the known compounds glyceryl-1-palmitate and daucosterol-6'-linoleate were isolated from the roots/rhizomes of Cimicifuga racemosa. The new compounds, designated as cimiracemosides I-P (1, 3-9), were determined by spectral analysis to be 7-dehydro-23-epi-12,26-dideoxyacteol-3-O-beta-D-xylopyranoside (1), 12-O-acetyl-25-anhydrocimigenol-3-O-alpha-L-arabinopyranoside (3), 12-O-acetyl-25-anhydrocimigenol-3-O-beta-D-xylopyranoside (4), 4',23-O-diacetylshengmanol-3-O-beta-D-xylopyranoside (5), 4',23-O-diacetylshengmanol-3-O-alpha-L-arabinopyranoside (6), 23-epi-acetylacteol-3-O-alpha-L-arabinopyranoside (7), 4'-O-acetyl-26-deoxyactein (8), and 16beta:23;24:25-diepoxy-12beta-O-acetyl-3beta-hydroxy-9,19-cyclolanost-23,26-olide-O- beta-D-xylopyranoside (9).

From the leaves and stems of Larrea tridentata six new furanoid lignans, compounds 1-6, have been isolated and their structures determined through interpretation of physical and spectroscopic properties. The use of 1D and 2D nOe experiments was of particular importance in assigning the stereochemistry.

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Background and purpose: Inflammatory response and cytokine activation are markedly stimulated after myocardial infarction, and contribute to cardiac remodelling. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic effects on cardiac remodelling. Adenosine, released by all cell types, binds to a class of G protein-coupled receptors to induce various cardiovascular effects. The aim of this work was to investigate whether activation of adenosine receptors, particularly A2B adenosine receptors, could stimulate IL-6 secretion in cardiac fibroblasts (CFs). Experimental approach: ELISA was used to assess IL-6 concentration in supernatant, and immunostaining was used to analyse IL-6 protein level in CFs. The levels of phosphorylated and total p38, extracellular signal-regulated kinase, c-Jun N-terminal kinase and protein kinase C-d (PKC-d) were determined by Western blot analysis. Key results: Adenosine-5′-N-ethyluronamide (NECA), a stable adenosine analogue, dose-and time-dependently stimulated IL-6 secretion in CFs. The effect of NECA was dose-dependently inhibited by an A2B antagonist, and silencing of the A2B receptor also inhibited IL-6 secretion. By using PKC isoform-selective inhibitors and translocation peptide inhibitors, the PKC-d isoform was found to be involved in the up-regulation of IL-6 production. Inhibition of p38 by SB203580, and adenoviral transfer of dominant-negative p38 inhibited NECA-induced IL-6 production. Furthermore, PKC-d functioned as an upstream regulator of p38 MAPK in this process. Conclusions and implications:We demonstrated a novel relationship between adenosine and IL-6 secretion, in that IL-6 secretion induced by NECA was mediated by adenosine A2B receptor activation in CFs and was dependent on a PKCd-P38 pathway.