Inhibition of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus.

Mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. Phellinus linteus has been used as a traditional herb medicine in oriental countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, roles of Phellinus linteus in the mast cell-mediated anaphylactic reactions have not fully been examined. In the present study, we have investigated the effects of water extract from the fruiting body of Phellinus linteus (WEPL) on mast cell-mediated anaphylaxis-like reactions. Oral administration of WEPL inhibited the compound 48/80-induced systemic anaphylaxis-like reaction and ear swelling response. WEPL also inhibited the anti-dinitrophenyl (DNP) IgE-mediated passive systemic and cutaneous anaphylaxis. WEPL had no cytotoxicity on rat peritoneal mast cells (RPMC). WEPL dose-dependently reduced histamine release from RPMC activated by compound 48/80 or anti-DNP IgE. Moreover, WEPL decreased the compound 48/80-induced calcium uptake into RPMC. Furthermore, WEPL increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced cAMP reduction in RPMC. These results suggest that WEPL may serve as an effective therapeutic agent for allergic diseases.

Double geminal C-H activation and reversible alpha-elimination in 2-aminopyridine iridium(III) complexes: the role of hydrides and solvent in flattening the free energy surface.

[H2Ir(OCMe2)2L2]BF4 (1) (L = PPh3), a preferred catalyst for tritiation of pharmaceuticals, reacts with model substrate 2-(dimethylamino)pyridine (py-NMe2; py = 2-pyridyl) to give chelate carbene [H2Ir(py-N(Me)CH=)L2]BF4 (2a) via cyclometalation, H2 loss, and reversible alpha-elimination. Agostic intermediate [H2Ir(py-N(Me)CH2-H)L2]BF4) (4a), seen by NMR, is predicted (DFT(B3PW91) computations) to give C-H oxidative addition to form the alkyl intermediate [(H)(eta2-H2)Ir(py-N(Me)CH2-)L2]BF4. Loss of H2 leads to the fully characterized alkyl [HIr(OCMe2)(py-N(Me)CH2-)L2]BF4 (3a(Me2CO)), which loses acetone to give alkylidene hydride 2a by rapid reversible alpha-elimination. 2a rapidly reacts with excess H2 in d6-acetone to generate [H2Ir(OC(CD3)2)2L2]BF4 (1-d12), 3a((CD3)2CO), and py-NMe2 in a 1:1:1 ratio, showing reversibility and accounting for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH2)4 gives the fully characterized carbene 2c. A cis-L(2) carbene intermediate, cis-2c, observed by NMR, reacts with CO via retro alpha-elimination to give the alkyl 3cCO, while the trans isomer, 2c, does not react; retro alpha-elimination thus requires the Ir-H bond to be orthogonal to the carbene plane. Consistent with experiment, computational studies show a particularly flat PE surface with activation of the agostic C-H bond giving a less stable H2 complex, then formation of a kinetic carbene complex with cis-L, only seen experimentally for py-N(CH2)4. Hydrides at key positions, together with gain or loss of solvent and H2, flatten the PE (DeltaG) surfaces to allow fast catalysis.