玉屏风散药效优于其同方汤剂的低极性分子组合缺失机制

目的: 揭示玉屏风散药效优于其同方汤剂的低极性分子组合缺失机制。 方法: 按玉屏风处方制备玉屏风散剂,用有机溶媒按极性大小依次提取,收集浓缩提取液,得玉屏风散剂石油醚、乙酸乙酯、正丁醇和水部位;按玉屏风方制备玉屏风汤剂,减压浓缩汤剂,用有机溶媒按极性大小依次萃取浓缩液,收集各浓缩萃取液,得玉屏风汤剂石油醚部位、乙酸乙酯部位、正丁醇部位和水部位;用高效液相色谱法表征玉屏风同方汤散方不同极性部位样品成分差异。小鼠按体重随机分组为正常对照组、模型组、汤剂组、散剂组、乙酸乙酯部位组和甲状腺素片对照组,正常组、模型组提前给药3 d后,除正常组外,其他各组分别腹腔注射10 mg环磷酰胺,同时继续给予前药,每天1次,连续5 d,于第6 d末次给药后30 min,将各组小鼠同时放入(-20±1)℃冰柜中,观察小鼠死亡时间。随机对照方法进行临床研究,试验组给予玉屏风散每次1.5 g,每日3次,口服,疗程4周;对照组给予黄芪30 g、白术15 g、防风15 g煎服,每日1剂,疗程4周。 结果: 散剂和汤剂水和正丁醇部位化学成分完全相同,重量相近,散剂和汤剂乙酸乙酯部位化学成分类别基本相同,但散剂比汤剂重量多9.5倍,散剂和汤剂石油醚部位成分类别相似,但重量上散剂石油醚部位比汤剂多450倍。与模型组相比,汤剂组能显著延长免疫低下小鼠的耐寒力,而散剂组可极显著延长免疫低下小鼠的耐寒力。给药4周治疗玉屏风散剂组疗效优于其同方汤剂对照组。 结论: 玉屏风散剂药效优于其同方汤剂的根本机制可能是玉屏风汤剂比其同方散剂缺失高达450倍的低极性分子组合。

Objective: To reveal the mechanism for the superiority in curative effect of Yupingfeng powder compared with the decoction with the same formulae. Methods: Yupingfeng powder was prepared based on the prescription,followed by extraction with a series of organic solvents in the order of increasing polarity.Extracts were collected and concentrated under vacuum to obtain petroleum ether,ethyl acetate,butanol and water extracts;Yupingfeng decoction was prepared according to the prescription followed by concentration under vacuum and successive extraction by petroleum ether,ethyl acetate and butanol.The corresponding organic extracts were obtained.Chemical composition differences in different polar sample parts were characterized by high performance liquid chromatography.Mice were randomly divided into normal group,model group,decoction group,powder group,ethyl acetate part group,and thyroxine tablet group by weight.Three days after oral administration of the drug given to the normal group and model group,all animals except those in the normal group were injected with 10 mg cyclophosphamide,meanwhile,the corresponding drug was also given once daily for 5 days.On the 6th day,30 minutes after the last drug administration,animals in all groups were put into a-20℃ refrigerator,and the death time of each animal was recorded.Randomized control method was used in clinical research.The experimental group was orally given 1.5 g Yupingfeng powder at a time,three times daily for 4 weeks;the control group was given decoction prepared from 30 g of Astragalus,15 g rhizome of Atractylodes Macrocephala,and 15 g of the root of saposhnikovia divaricata daily for 4 weeks. Results: Both the weight and chemical constituents in water and n-butanol parts of decoction and powder were exactly the same.Chemical constituents in ethyl acetate parts of the powder were similar to those in the decoctions,but the weight of the acetate parts of powder was 9.5 times higher than that of the decoction.Although the chemical constituents of the petroleum part of the powder were similar to those of the decoction,in terms of weight,the petroleum part of the powder was 450 times higher than that of the decoction.Decoction treatment could significantly extend the immunity of mice with low cold hardiness,and powder treatment could extremely significantly extend the immunity of mice with low cold hardiness compared with the model groups.After 4 weeks of treatment,the Yupingfeng powder group showed better curative effect than the decoction control group;compared with the model groups the decoction group significantly extended the cold hardiness in immunodepressed mice,compared with powder,Yupingfeng decoction was lower by 450 times in combinations of low-polar molecules. Conclusion: The deletion of the low-polar molecules in the Yupingfeng decoction can be the fundamental mechanism responsible for the superiority in efficacy of Yupingfeng powder comparing with the decoction.