| Objective To observe the optimization function of the compound combination with three elements monomer(luteolin, baicalein, quercetin) the treatment of chronic pharyngitis and its preferred dosage.This study can provide the experimental basis for the further research and development application.Methods 1 The experimental arrangement is finished by the three factors and three levels orthogonal experiment table L9(34) by using three different doses of luteolin,quercetin and baicalein. Xylene-induced mice ear edema were observed. Observing the relationship of three factors and obtaining the optimal dosage. 2 Verification pharmacodynamic experiments of the compound combination with three elements monome: 1) Anti inflammatory and analgesic experiments:(1) We observed the effect of three elements by mice pain by hot plate test and writhing test.(2) Effect of three elements on rat paw edema induced by carrageenan.(3) Effect of three elements on rat cotton ball granuloma. 2) Verification pharmacodynamic experiments of the antitussive and expectorant:(1) The Influences of three elements monomer on mouse cough induced by ammonia water.(2) The effects of three elements monomer on mouse phenolsulfonphthalein excretion. 3) The anti-inflammatory effect on chronic pharyngitis in rabbits: The rabbit model of chronic pharyngitis indused by ammonia and turpentine to observe.(1) Effects of three elements monomer on general condition in chronic pharyngitis rabbits.(2) Effects of three element monomer on throat performance in chronic pharyngitis rabbits.(3) Effects of three element monomer on the pathological changes of the throat pathological changes in chronic pharyngitis rabbits.Results 1 The orthogonal test showed that mice ear edema in 9 combination groups were lower than in the control group.The best combination of three elemtns is luteolin high dose(40mg/kg), baicalein medium dose(30mg/kg) and quercetin medium dose(10mg/kg). And the ratio of three is 4:3:1. 2 According to the best combination of orthogonal test, combination of the Luteolin 40 mg, Baicalein 30 mg, Quercetin 10 mg is adistered dose(80 mg/kg), The middle dose x 0.5 is low dose(40 mg/kg), medium dose x2 is high dose(160 mg/kg). 3 We intervened the experimental animals and carried out the pharmacodynamics experiments. 1) The analgesic experiments: compared with control,Three prime monomer compound inhibited the pain which induesd bu heat stimulation(hot plate method) and chemical stimulation(writhing), showed an obvious dose effect relationship. Three element compound can obviously prolong the pain threshold with the increase of dosage, the low, medium, high dose group increased the percentage of pain threshold were 62.46%, 131.09% and 143.38%, Aspirin pain threshold was the highest of the 180.06%. Compared with control, high dose, middle dose of three elements compound could significantly prolong the pain latency that caused by chemical stimulation and significantly reduce the writhing times of the mice, P<0.05 or P<0.01,but slightly weaker than the aspirin group. 2) The anti-inflammatory experiments:(1)Anti-inflammatory indicators verified that optimal dosage could decreased xyleneinduced mice ear edema,as the dose increased, the inhibition rate(8.89%, 36.67%,38.89%) also increased. The high dose and middle dose were similar as aspirin(41.11%),but the three groups had no difference(P>0.05).(2) The results of the three elements monomer on paw swelling indused by carrageenan in rats showed, compared to the control group, middle dose, high dose could obviously inhibit the foot swelling degree,P<0.05, prolonged inhibitory effect more obvious over time.Swelling in the aspirin group and in the high dose and middle dose group of three elements monomer, 4h is starting to fade, 6h significantly subsided. Swelling inhibition rate of aspirin is the most obvious,The high dose and middle dose inhibition rate of three elements compound was slightly lower than the aspirin.(3)The results of the three elements monomer on cotton ball granuloma in rats showed, compared to the control group, the high dose and middle dose could obviously inhibit the cotton ball granuloma, P<0.01, the middle dose inhibition rate was 22.35%, high dose inhibition rate was 21.13%, dexamethasone inhibition rate was23.44%, no differences among the three(P>0.05). 3) Antitussive experiments and Expectorant experiment.(1) compared to the control group, In the low, middle, high dose and Maxing Cough Syrup positive could prolong the latent period of cough(P<0.01), and significantly reduced the frequency of cough in mice(P<0.01). There were obvious dose effect relationship, no significant difference between thes high doe group and the positive control(P>0.05).(2) Expectorant effect: The phenolsulfonphthalein excretion results of the three elements monomer on mice, compared to the control group, phenol sulfonphthalein concentration was significantly higher(P<0.05, P<0.01) in the low,middle,high dose and Maxing Cough Syrup groups. There was no significant difference among the groups(P>0.05), but each phenol sulfonphthalein excretion concentrations were lower than the positive control Maxing Cough Syrup group(P<0.05, P<0.01). 4)The experimental animal models of chronic pharyngitis:It also could significantly improved the chronic pharyngitis symptoms In rabbits induced by ammonia and turpentine.(1) Compared with the model group, rabbits eating and body weight growth rate were higher in each drug treatment group, the middle dose, high dose and huangshixiangsheng pills groups were more obvious in P<0.05.(2) Compared with the model group, the number white blood cells, lymphocytes and granulocytes in the blood showed a decrease in varying degrees of each drug treatment group, the middle dose,high dose and huangshixiangsheng pills groups decreased obviously(P<0.05, P<0.01).(3) Compared with the model group, drugs could relieved the mucosal pathological injury of throat in each treatment group. The effect of medium and high dose groups were better(P<0.01).Conclusions According to the proportion of 4:3:1 of the compound combination with luteolin, baicalein and quercetin which had analgesic, anti-inflammatory, antitussive,expectorant effects obvious. It showed a good therapeutic effect on chronic pharyngitis in a dose-dependent manner. |
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