药对网络中社团的网络特征数值分析

利用网络科学技术刻画中医理论有助于中药配伍研究的现代化和程序化。该文通过药对网络表示药物之间的直接作用关系,然后分析该网络的社团特征与血气功效的映射关系,最后以方剂为桥梁研究了血气理论在药对网络上的网络表达。研究发现,药对网络具有强的社团结构特征,每个社团由一系列关联紧密的药对组成。社团在药对功效上具有明显的理血和理气功效的相斥性,即同一个社团基本不会同时出现理血功效的药对和理气功效的药对,或者二者均不出现。由此将药对网络所涉及的386个单味中药划分成3类社团:理血(B)社团、理气(Q)社团和灰色社团。把262首方剂依次映射在这3类社团上的统计结果表明,如果一个方剂包含Q社团单味中药,那么它以99.84%的概率也包含B社团的单味中药;同时包含B和Q社团单味中药的方剂数量为140首。因此,对于一个方剂所包含的单味药物满足"有Q就有B,有B未必有Q"的规律,这个数值规律完全吻合中医的血气理论:理气必理血,理血未必理气(出血若因外伤或血热,那么理气就会加重出血)。一方面该文寻找到具有高辨识度的宏观网络数值特征,可以为判断新方剂合理性提供网络数值参考;另一方面论文从数值分析的角度证明了人体血与气的关系。     

基于AMDIS和保留指数结合的GC-MS技术定性鉴别醋炙前后香附-艾叶药对中挥发油化学成分的变化

目的 从药对的整体角度切入,以调经止痛的功效为评价模型,来探究醋炙对香附-艾叶药对整体配伍的影响。方法 采用GC-MS结合AMDIS与保留指数鉴别方法并联合主成分分析寻找共性规律的研究策略,全面系统地分析了醋炙前后香附-艾叶药对中挥发油化学成分的变化。结果 香附-艾叶（生品）挥发油中共鉴别出54种化学成分,而香附-艾叶（醋品）挥发油中共鉴别出52种化学成分。醋炙前后的香附-艾叶药对与醋炙前后的单味药中挥发油化学成分的变化并不一致。从整体来看,在醋香附-醋艾叶药对的挥发油中,多数低沸点化合物的含量降低,而高沸点化合物无明显变化,且大部分低沸点化合物主要归属于艾叶,大部分高沸点化合物主要归属于香附,α-香附酮的相对含量也有所增加。在醋香附-醋艾叶药对的挥发油中含量明显增加的化合物多为去氧倍半萜类化合物、长链脂肪醇和长链脂肪酮,而萜类氧化衍生物的含量则有所降低。结论 采用GC-MS结合AMDIS与保留指数鉴别方法并联合主成分分析寻找共性规律的研究策略,可全面、科学和快速地鉴别醋炙前后香附-艾叶药对中挥发油的差异。从整体上看,醋炙使得香附-艾叶药对中挥发油的毒性减小,安全性增加,稳固并小幅增强了调经止痛的功效。      

Potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting efflux transporter P-glycoprotein

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite.In this study,potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches.In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein(P-gp),as well as the inhibition effects on P-gp.Additionally,anti-inflammatory activity of aconitine(AC)combined with active ingredients of liquorice,as well as pharmacokinetic patterns of AC after co-administration was investigated.Anti-inflammatory effect of AC(1 mg/kg)in rats was enhanced in combination with bioactive ingredients of liquorice(10 mg/kg).In the meanwhile,the exposure of AC in vivo was altered,in terms of Cmax and AUC.For instance,the Cmax and AUC were increased to 1.9 and 1.3 folds,respectively,when used in combination with liquiritigenin.The in silico study revealed the potential binding mode with outward facing conformation of P-gp.The resulting data obtained from transport of rhodamine-123(Rh-123)across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice.The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp.The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation,and further the anti-inflammatory effect,which helps clarify the compatibility rationale of these two herbs.     

以黄芪-山茱萸治疗糖尿病肾病为例探究药对研究的新策略

药对具有复方配伍的最基本特点,是复方配伍中的最小单元。近年来,药对研究一直备受广泛关注,它是中医药现代化过程中不可或缺的一部分。随着新药创制效率的降低,如何从传统的中药药对中挖掘新药也一直是药物研发的难点之一。该文综述了近年的国内外文献,总结并归纳了药对研究的现状及问题。以此为基础,创新性地提出了"精准药对"的概念。"精准药对"不同于以往作用广和药效不明确的药对或复方,而是基于某种特定的疾病而开发的新的小药对,它作用明确且成分相对清楚。此外,作者还提出了"药对-结合柱色谱分离和细胞相关的成分谱筛选-模糊靶标识别药理学-精准药对再评价"的新策略,并成功将其应用于黄芪-山茱萸治疗糖尿病肾病的精准药对开发中。这种新策略简单、易操作且适用范围广,可为药对的现代研究及新药的研发提供借鉴和思考。     

附子-甘草药对配伍研究进展

中药配伍是中医用药的一大特色,合理的中药配伍可以达到减毒增效的效果。附子-甘草作为经典药对,已广泛应用于临床。文章通过综述近些年来中药药对附子-甘草的研究概况,并参考现代研究文献,从化学成分的相互作用(包括影响附子毒性成分的溶出)、与毒性成分形成沉淀或复合物、影响毒性成分在体内的吸收、分布、代谢、排泄等药代动力学过程以及配伍后对附子原有药效的影响几个方面阐释了附子-甘草配伍减毒存效的作用机制,并用中医药传统药性理论“四气五味”解释了附子-甘草配伍的科学内涵,以期以这一经典药对为切入点探讨中药配伍的意义。     

中药药对的系统研究（Ⅲ）——药剂学理论和新制剂开发

药对作为中药复方制剂的基础,以"同类相须、相辅相成、相反相成、相制为用"等原则配对,因其配伍相对简单而又能体现复方特色,近年来受到业界人士广泛关注。本文从中药药对的药剂基本理论如增溶、靶向及药动学行为改变等,以及其新型药物传递系统的研究概况进行综述,为中药药对配伍理论和应用提供新的药剂学诠释。在中医药基本理论的指导下,基于药对配伍的药剂学认识,以改进中药制剂与创新中药制剂并举,为丰富药对配伍的药剂学理论与现代药剂学相关联的新型中药药对制剂提出新见解。     

Study on intestinal absorption and pharmacokinetic characterization of diester diterpenoid alkaloids in precipitation derived from Fuzi–Gancao herb-pair decoction for its potential interaction mechanism investigation

Ethnopharmacological relevance

Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating.

Aim of study

In present study, we focus on Fuzi–Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi–Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated.

Materials and methods

Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed.

Results

In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1^st order absorption and lag time.

Conclusions

Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi–Gancao herb-pair.     

基于单味药及药对HPLC 指纹图谱探讨小青龙汤组方特性

小青龙汤方出自张仲景《伤寒论》,其组成为麻黄、芍药、细辛、干姜、甘草、桂枝、半夏、五味子。对单味药以及麻黄-甘草药对、麻黄-桂枝药对、白芍-桂枝药对、白芍-甘草药对、五味子-细辛药对的高效液相色谱（HPLC）指纹图谱分析研究逐渐深入。本文从此角度出发分析小青龙汤组方特性,探讨中医方剂配伍科学内涵。