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As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.

A Lewis base catalyst Trip-SMe (Trip = triptycenyl) for electrophilic aromatic halogenation using N-halosuccinimides (NXS) is introduced. In the presence of an appropriate activator (as a noncoordinating-anion source), a series of unactivated aromatic compounds were halogenated at ambient temperature using NXS. This catalytic system was applicable to transformations that are currently unachievable except for the use of Br2 or Cl2: e.g., multihalogenation of naphthalene, regioselective bromination of BINOL, etc. Controlled experiments revealed that the triptycenyl substituent exerts a crucial role for the catalytic activity, and kinetic experiments implied the occurrence of a sulfonium salt [Trip-S(Me)Br][SbF6] as an active species. Compared to simple dialkyl sulfides, Trip-SMe exhibited a significant charge-separated ion pair character within the halonium complex whose structural information was obtained by the single-crystal X-ray analysis. A preliminary computational study disclosed that the π system of the triptycenyl functionality is a key motif to consolidate the enhancement of electrophilicity.

A Lewis base catalyst Trip-SMe (Trip = triptycenyl) for electrophilic aromatic halogenation using

The histamine H(1) receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKCδ-selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976, an inhibitor of Ca(2+)-dependent PKCs, did not. Histamine or PMA stimulation resulted in PKCδ phosphorylation at Tyr(311) and Thr(505). Activation of PKCδ by H(2)O(2) resulted in H1R mRNA up-regulation. Overexpression of PKCδ enhanced up-regulation of H1R gene expression, and knockdown of the PKCδ gene suppressed this up-regulation. Histamine or PMA caused translocation PKCδ from the cytosol to the Golgi. U0126, an MEK inhibitor, and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up-regulation of H1R gene expression. These results were confirmed by a luciferase assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA was also observed. However, real-time PCR analysis showed no inhibition of H1R mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of the PKCδ/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or PMA-induced up-regulation of H1R gene expression in HeLa cells.

Chlorocobalt(III) porphyrins showed novel UV-vis and 1H NMR spectra in a non-coordinating solvent to suggest displacement of the cobalt out of the porphyrin plane toward the axial ligand in solution. They underwent insertion of alkynes into the Co–Cl bond to generate σ-(trans-2-chlorovinyl)cobalt(III) complexes. In a special case, novel [4+2]cycloaddition reaction between the Co–N–C(pyrrole-α)-C(meso) moiety of [CoIIICl(oep)] [oep = octaethylporphyrin dianion] and dimethyl acetylenedicarboxylate took place. The reaction behavior of chlorocobalt(III) porphyrins was compared with that of diaquaperchloratocobalt(III) porphyrins which also reacted with alkynes in the presence of 2,6-lutidine to give analogous σ-vinylcobalt(III) porphyrins with a 2,6-dimethyl-1-pyridinio substituent occupying the trans-β-position of the σ-vinyl group. While the methoxycarbonyl group of methyl propiolate was directed to the α side of these σ-vinylcobalt(III) complexes, the phenyl group of phenylacetylene was found to be directe...

Novel organocobalt(III) porphyrins with an alkyne inserted into an N-Co bond of diaquo(porphyrinato) cobalt(III) perchlorates could be isolated by using dimethyl acetylenedicarboxylate and methyl propiolate. These complexes were converted into N 21 , N 22 (etheno-bridged porphyrins through the oxidative cobalt-to-nitrogen shift of the vinylic carbon when treated with excess FeCl 3 . Cobalt(III) prophyrin π cation radicals with a weakly coordinating axial ligand reacted smoothly with diphenylacetylene directly to afford the N 21 , N 22 -etheno-bridged porphyrin in good yields

The alignment of a nematic liquid crystal (LC) was changed reversibly by a photochromic reaction of vinyl-polymer films bearing azobenzene (Az) chromophores. Photoisomerization of Az in the polymer films proceeded slower than in solution systems with an irreversible nature, due to a limited free volume of polymers and the presence of Az aggregates. Photoregulative Az films were obtained by two procedures: (i) spin-coating followed by baking processes: and (ii) adsorption from a LC/polymer mixture onto a lecithin-coated glass surface. Perpendicular alignment, which is achieved both in the surface Az and in the LC layer, allows a parallel interaction between them and enables the photoregulation of the LC alignment.

Acetylene is reversibly inserted into a Co–N bond of bis(aquo)octaethylporphyrinatocobalt(III) perchlorate, (OEP)CoIII(H2O)2ClO4 (1), in CH2Cl2 solution, generating a d6 high spin (S = 2) complex. Addition of 2,6-lutidine to a mixture of 1 and acetylene gave a σ-vinylcobalt(III) complex, (OEP)CoIII–CH=CH–L+ClO4 [L = 2,6-lutidine], whereas pyridine replaced the acetylene ligand to afford (OEP)CoIII(PY)2ClO4. These results suggest the intermediacy of a CoIII acetylene π-complex.

Reaction de OEP Co(III) (H 2 O) 2 ClO 4 avec un exces d'acetylenique R 1 C≡CR 2 en presence de FeCl 3 dans CH 2 Cl 2 et lavage a HClO 4 . OEP=l'octaethyl porphyrine. R 1 =H,CH 2 OH,C 6 H 5 et R 2 =H,n-C 4 H 9 ,CH 2 OH,C 6 H 5