壮药战骨总黄酮提取物经皮给药对大鼠/小鼠的抗炎、镇痛作用研究

Study on Anti-inflammatory and Analgesic Effects of Total Flavonoids Extract of Zhuang Medicine Premna fulva for Rats/Mice by Transdermal Administration

目的:研究壮药战骨总黄酮提取物经皮给药的抗炎、镇痛作用,为战骨经皮给药新制剂的研发提供参考。方法:分别将小鼠和大鼠分为空白组(40%乙醇溶液)、阳性对照组(双氯酚酸二乙胺,小鼠的给药剂量为0.390 g/kg、大鼠为0.280 g/kg)和战骨总黄酮提取物低、中、高剂量组(以生药计小鼠的给药剂量为0.400、0.791、6.330 g/kg,大鼠为0.136、0.275、2.200 g/kg)。腹部经皮给药,每天给药1次。分别采用二甲苯致炎法测定小鼠耳肿胀率(给药5 d)和弗氏完全佐剂致炎法测定致炎2、4、9、15 d后大鼠的足趾肿胀度(给药18 d),以考察战骨总黄酮提取物的抗炎作用。采用乙酸扭体法测定小鼠注射1%乙酸后20 min内的扭体次数(给药5 d),末次给药后30、60、90 min采用热板致痛法测定小鼠的疼痛抑制率(给药5 d),光热甩尾法测定大鼠的可能最大镇痛百分率(给药18 d)以及鼠尾压痛法测定小鼠的痛阈提高值(给药5 d),以综合评价战骨总黄酮提取物的镇痛作用。结果:与空白组比较,战骨总黄酮提取物高剂量组小鼠耳肿胀率和致炎不同时间后大鼠的足趾肿胀度显著降低(P<0.05或P<0.01),小鼠扭体次数显著减少(P<0.01),给药不同时间后小鼠的疼痛抑制率以及可能最大镇痛百分率和痛阈提高值均显著升高(P<0.05或P<0.01);战骨总黄酮提取物中剂量组大鼠在致炎2、4、9 d的足趾肿胀度显著降低(P<0.05或P<0.01),小鼠扭体次数显著减少(P<0.01),末次给药后60、90 min的小鼠疼痛抑制率和痛阈提高值显著升高(P<0.05或P<0.01);战骨总黄酮提取物低剂量组大鼠在致炎2、4、9 d的足趾肿胀度显著降低(P<0.05或P<0.01),给药后90 min的疼痛抑制率显著升高(P<0.01)。结论:战骨总黄酮提取物经皮给药具有明显的抗炎、镇痛作用,且呈现一定的量效关系。

OBJECTIVE:To study anti-inflammatory and analgesic effects of total flavonoids extract of Zhuang medicine Premna fulva for rats/mice by transdermal administration,and to provide reference for R&D of new preparation extract of P.fulva by transdermal administration.METHODS:Mice and rats were divided into blank group(40%Ethanol solution),positive control group(diclofenac diethylamine,0.390 g/kg for mice,0.280 g/kg for rats),total flavonoids extract of P.fulva low-dose,medium-dose and high-dose groups(0.400,0.791,6.330 g/kg for mice,0.136,0.275,2.200 g/kg for rats,calculated by crude drug)respectively.They were given medicine by transdermal administration,once a day.Ear swelling rate of mice was determined by xylene-induced inflammation method(5 d after administration).The inflammation method with Freund’s complete adjuvant was used to determine the degree of paw edema in rats 2,4,9,15 d after inducing inflammation(18 d after medication)so as to investigate anti-inflammatory effects of total flavonoids extract of P.fulva.The times of twisting in mice was determined by acetic acid-induced writhing method after injection of acetic acid in 20 min(5 d after medication)after.Inhibitory rate of pain in mice was determined by hot plate-induced pain method 30,60,90 min after last administration(5 d after medication).Potential maximal analgesia percentage of rats was determined by light tail-flick method(18 d after medication),and the improvement of pain threshold was determined in by mice tail tenderness method(5 d after medication).Analgesic effects of total flavonoids extract of P.fulva were evaluated comprehensively.RESULTS:Compared with blank group,the ear swelling rate in mice and paw edema of rats at different time points of inflammation were decreased significantly in total flavonoids extract of P.fulva high-dose group(P<0.05 or P<0.01),while the writhing times of mice was decreased significantly(P<0.01);inhibitory rate of pain at different times,potential maximal analgesia percentage and the improvement of pain threshold in mice were improved significantly(P<0.05 or P<0.01).The degree of paw edema in rats was decreased significantly 2,4,9 d after inducing inflammation in total flavonoids extract of P.fulva medium-dose group(P<0.05 or P<0.01);the writhing times of mice was decreased significantly(P<0.01);inhibitory rate of pain and the improvement of pain threshold in mice were both increased significantly 60,90 min after last administration(P<0.05 or P<0.01).The degree of paw edema in rats was decreased significantly 2,4,9 d after inducing inflammation in total flavonoids of P.fulva low-dose group(P<0.05 or P<0.01),while inhibitory rate of pain was increased significantly 90 min after medication(P<0.01).CONCLUSIONS:The total flavonoids extract of P.fulva by transdermal administration have significant anti-inflammatory and analgesic effect,with a dose-response relationship.