The capsaicin-sensitive vanilloid receptor (VR1) was recently shown to play an important role in inflammatory pain (hyperalgesia), but the underlying mechanism is unknown. We hypothesized that pain-producing inflammatory mediators activate capsaicin receptors by inducing the production of fatty acid agonists of VR1. This study demonstrates that bradykinin, acting at B2 bradykinin receptors, excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid . This finding identifies a mechanism that might be targeted in the development of new therapeutic strategies for the treatment of inflammatory pain.

The bioassay-directed isolation of a marine brown alga, Ecklonia cava, afforded four phlorotannin derivatives, eckol (1), 8,8′-bieckol (2), 8,4′′′-dieckol (3), and phlorofucofuroeckol A (4). Among these compounds, 2 and 3 exhibited an inhibitory effect on human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease. Specifically, they inhibited the RT more potently than the protease. The inhibitory activity of compound 2 (IC50, 0.51 μM) against HIV-1 RT was comparable to that of nevirapine (IC50, 0.28 μM), a reference compound. An enzyme kinetic assay showed that this compound inhibited the RNA-dependent DNA synthesis activity of HIV-1 RT noncompetitively against dUTP/dTTP with a Ki value of 0.78 μM. With respect to the homopolymeric template/primer, (rA)n(dT)15, 8,8′-bieckol (2) displayed an uncompetitive type of inhibition (Ki, 0.23 μM).

The bioassay-directed isolation of Terminalia chebula fruits afforded four human immunodeficiency virus type 1 (HIV-1) integrase inhibitors, gallic acid (1) and three galloyl glucoses (2 - 4). In addition, four flavonol glycoside gallates (5 - 8) from Euphorbia pekinensis containing the galloyl moiety also showed the inhibitory activity at a level comparable to those of 2 - 4. By comparison with the activities of the compounds not bearing this moiety, it is proposed that the galloyl moiety plays a major role for inhibition against the 3′-processing of HIV-1 integrase of these compounds.