We discovered a phenomenon in which the blood flow in vein microcirculation markedly decreases in response to hen-egg white lysozyme (HEL)-sensitization without any change in blood pressure. Using this blood flow decrease as a guide, we developed an in vivo assay method to search for substances, which can prevent allergies. Antagonists of histamine, serotonin and platelet activating factor (PAF) did not affect the blood flow decrease in response to HEL-sensitization. On the other hand, cyclooxygenase (COX)-1, COX-2, thromboxane (TX) A 2 , endothelin-1 (ET-1), prostacyclin (PGI 2 ) and granulocytic elastase (GE) as well as nitric oxide (NO) from inducible NO synthase (iNOS) were involved in the blood flow decrease. Thus, these substances might injure vascular endothelial cells, and cause a decrease in blood flow in vein microcirculation. Our method can be used to search for preventive agents against allergies involving NO, COX-1, 2 and PGI 2 . This is the first report to applying to an assay method the specific blood flow decrease to occur in the promotion stage of allergy.
A 35% EtOH extract of the fruits of Chaenomeles sinensis, long utilized as a folk medicine for cough, significantly inhibited the pruritogenic agent compound 48/80 (COM)-induced scratching behavior in mice. Antipruritic activity-guided fractionation and purification yielded active quercetin, apigenin, and catechin derivatives, which exhibited significant inhibitory effects on COM-induced scratching behavior. To the best of our knowledge, apigenin (5), apigenin 7-glucronide (6), and apigenin 4'-methoxy-7-glucronide (acacetin 7-glucronide) (7) were isolated from the fruits of C. sinensis for the first time. The active fraction and these compounds also inhibited serotonin-, platelet activating factor-, and prostaglandin E(2)-induced scratching behavior, but did not inhibit histamine-induced scratching behavior or locomotive behavior. This study also showed that the fruits of C. sinensis could be used to treat allergic itching sensation.
A 35% EtOH extract of flowers of Impatiens textori MIQ. showed an inhibitory effect on blood pressure decrease in response to platelet activating factor (PAF) measured with a blood pressure monitoring system. Bioassay-guided fractionation of the 35% EtOH extract (IT) led to isolation of the flavones apigenin (1) and luteolin (3), which significantly inhibited blood pressure decrease in response to PAF. Their compounds and apigenin 7-glucoside (2), chrysoeriol (4), quercetin (5), quercetin 3-glucoside (6), kaempferol (7), kaempferol 3-glucoside (8) and kaempferol 3-rhamnosyldiglucoside (9) were also isolated from the flowers of I. textori for the first time. This study revealed that the flowers of I. textori might be a possible anti-allergy agent.
The inhibitory effects of 22 xanthones from three Guttiferae plants (Hypericum patulum, Calophyllum inophyllum and C. austroindium) on exogenous platelet activating factor (PAF)-induced hypotension were examined using a blood pressure monitoring in vivo assay method. Guanandin (2), caloxanthone E (3), 1,3,5,6-tetrahydroxy-2-isoprenylxanthone (8), 6-deoxyjacareubin (11) and patulone (18) showed strong inhibition of PAF-induced hypotension, with inhibitory effects of more than 60 %. Their ID50 values were greater than that of ginkgolide B (BN-52 021), a natural PAF-antagonist from the Ginkgo biloba.
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