论文部分内容阅读
目的探究以马钱子、麻黄生物碱为主要部位的7种腰痛宁衍生方的细胞药理活性,并对细胞模型下有优效的组方进行体内药效学评价。方法以50%马钱子生物碱+50%麻黄生物碱为组方基础,分别与腰痛宁胶囊组方药材及8种常用风湿骨病组方中药的总黄酮、总皂苷、总挥发油/水提物及总多糖有效部位组合成7个样品,同时以腰痛宁加黄酒药引为对照。测定各样品抑制小鼠巨噬细胞中前列腺素E2(PGE2)增殖的IC50及促进小鼠巨噬细胞中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)及肿瘤坏死因子(TNF-α)增殖的EC50,并进行比较。同时采用最小二乘优化方法,计算各样品的EC50或IC50叠加值,根据EC50或IC50实验值和叠加值之间的差异分析各有效部位间的相互作用关系。采用小鼠耳肿胀模型和小鼠皮肤迟发型超敏反应(DTH)模型进行最优组合的体内药效学评价。结果 25%马钱子生物碱+25%麻黄生物碱与总黄酮组合(4号样品)具有最佳的综合细胞抗炎、免疫调节活性,且各模型下该组方中有效部位间有极强的协同作用;25%马钱子生物碱+25%麻黄生物碱分别与总皂苷、总挥发油/水提物及总多糖组合样品(5、6、7号样品)的抗炎活性与4号样品相当;5和7号样品有良好的综合免疫调节活性;25%马钱子生物碱+25%麻黄生物碱以及马钱子生物碱或麻黄生物碱与总黄酮组合样品(1、2、3号样品)的药理活性均显著弱于4号样品;小鼠体内药效学实验表明将4号样品组合中25%马钱子生物碱+25%麻黄生物碱比例降为25%及5%时,具有较好的抗炎、免疫作用。结论马钱子生物碱不宜单独与麻黄生物碱配伍,2种生物碱不宜单独与总黄酮配伍,25%马钱子生物碱+25%麻黄生物碱与总黄酮、总皂苷、总挥发油/水提物及总多糖分别组合通常会产生协同或叠加作用,有助于增强25%马钱子生物碱+25%麻黄生物碱的细胞药理活性,25%马钱子生物碱+25%麻黄生物碱与总黄酮组合样品的细胞抗炎和免疫调节活性在小鼠体内亦得到体现,提示根据细胞实验结果筛选优化中药组方具有可行性。
Objective To explore the pharmacological activities of 7 kinds of Yaotongning Decoction, the main part of which contains Strychnos nux vomica and Ephedra alkaloids, and to evaluate the pharmacodynamics of the prescriptions with good effects under the cell model in vivo. Methods 50% Strychnos alkaloids + 50% ephedrine alkaloids were used as the basis of the group. The contents of total flavonoids, total saponins, total volatile oil And total polysaccharide effective part of the combination of seven samples, while the reference to the low back pain Ning Huang rice wine as a control. The IC50 of each sample for inhibiting the proliferation of prostaglandin E2 (PGE2) in mouse macrophages and the levels of interleukin-6 (IL-6), interleukin-1β The EC50 of proliferation of necrosis factor (TNF-α) was compared and compared. At the same time, the least square method was used to calculate the EC50 or IC50 value of each sample. The interaction between the effective fractions was analyzed according to the difference between the EC50 or IC50 values and the superposition values. An optimal combination of in vivo pharmacodynamic evaluations was performed using a mouse ear swollen model and a mouse cutaneous delayed type hypersensitivity (DTH) model. Results 25% Strychnos alkaloids + 25% ephedrine alkaloids combined with total flavonoids (No.4 sample) had the best combination of anti-inflammatory and immunomodulatory activities in cells. The anti-inflammatory activity of 25% Strychnos alkaloids + 25% ephedrine alkaloids with total saponins, total volatile oil / water extract and polysaccharides (samples Nos. 5, 6, and 7) Equivalent; 5 and 7 samples have good comprehensive immunomodulatory activity; 25% Strychnos alkaloids + 25% ephedrine alkaloids and strychnos alkaloids or ephedrine alkaloids and flavonoids combination samples (1,2,3 The pharmacological activity of the sample was significantly weaker than that of the sample No. 4. In vivo pharmacodynamic experiments in mice showed that when the proportion of 25% Strychnos alkaloids + 25% ephedrine alkaloids was reduced to 25% and 5% in the sample No. 4, Has a good anti-inflammatory, immune function. Conclusion Strychnos alkaloids should not be combined with Ephedra alkaloids alone. The two alkaloids should not be combined with total flavonoids alone. 25% Strychnos alkaloids + 25% ephedrine alkaloids with total flavonoids, total saponins, total volatile oil / water The combination of polysaccharides and total polysaccharides, respectively, usually produces a synergistic or additive effect, which helps to enhance the cytotoxic activity of the 25% Strychnos alkaloids + 25% Ephedra alkaloids. The 25% Strychnos alkaloids + 25% ephedrine alkaloids and The anti-inflammatory and immunomodulatory activities of the total flavonoids in the samples were also demonstrated in mice, suggesting that it is feasible to screen and optimize the traditional Chinese medicine prescriptions based on the cell experiment results.