药学学报, 2021, 56(8): 2112-2118
引用本文:
朱耀萱, 陈伟, 王振中, 乔宏志, 狄留庆. 麻杏石甘汤抗菌活性的空间异质性及其物理结构基础[J]. 药学学报, 2021, 56(8): 2112-2118.
ZHU Yao-xuan, CHEN Wei, Wang Zhen-zhong, QIAO Hong-zhi, DI Liu-qing. Spatial heterogeneity and physical structure basis of antibacterial activity of Ma-Xing-Shi-Gan Decoction[J]. Acta Pharmaceutica Sinica, 2021, 56(8): 2112-2118.

麻杏石甘汤抗菌活性的空间异质性及其物理结构基础
朱耀萱1, 陈伟2, 王振中3,4, 乔宏志1,3,4*, 狄留庆1*
1. 南京中医药大学药学院, 江苏省中药高效给药系统工程技术研究中心, 江苏 南京 210023;
2. 南京中医药大学附属南京医院临床科研中心, 江苏 南京 210003;
3. 江苏康缘药业股份有限公司, 江苏 连云港 222001;
4. 中药制药过程新技术国家重点实验室, 江苏 连云港 222001
摘要:
麻杏石甘汤为经典方药,但方中多成分间的互作关系和相态变化不清,多成分物理相态与药效的关联性不明。本研究实时监测麻杏石甘汤煎煮过程中的粒径变化,采用离心法分离不同相态并分析其组成分布和抗菌活性;引入化学干扰剂配合粒度和形貌观察明确多成分物理相态的互作力类型,研究抗菌活性与相态物理结构的关联性。结果显示,麻杏石甘汤煎煮过程中颗粒的混杂度下降,粒度分布变窄并最终稳定在170 nm附近,有机和无机成分在各相态间呈非均匀分布;经13 500×g离心后所得的上清液(S-13500相态)抗菌活性最佳,其含有麻黄碱、苦杏仁苷和甘草酸等有机活性小分子和Ca、K、Mg等无机成分;活性物理相态中的分子互作力主要为疏水相互作用和氢键作用,破坏互作力将导致相态结构变化和体内外抗菌活性的下降。本研究证实,麻杏石甘汤煎煮过程中化学成分交织互作形成了新的物理相态,导致汤剂成分的异质性分布。活性相态的抗菌活性由其化学成分和物理结构共同决定,为中药药效的物理基础提供了直接证据。
关键词:    麻杏石甘汤      自沉淀      相态      物理结构      抗菌      互作机制      超分子      结构中药学     
Spatial heterogeneity and physical structure basis of antibacterial activity of Ma-Xing-Shi-Gan Decoction
ZHU Yao-xuan1, CHEN Wei2, Wang Zhen-zhong3,4, QIAO Hong-zhi1,3,4*, DI Liu-qing1*
1. Jiangsu Engineering Research Center for Efficient Delivery System of TCM, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China;
2. Clinical Research Center, Nanjing Hospital affiliated to Nanjing University of Chinese Medicine, Nanjing 210003, China;
3. Jangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China;
4. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, China
Abstract:
Ma-Xing-Shi-Gan Decoction is a classic prescription. However, the interaction among multiple components of the decoction and the change of phase state are not clear. Moreover, the relationship between the physical phase state aggregated by multiple components and the efficacy still needs to be studied. In this study, we monitored the particle size changes of Ma-Xing-Shi-Gan Decoction in real time. Then we isolated different phase states by centrifugation, analyzed their composition distribution and tested their antibacterial activity. We added chemical interference agents to investigate the interaction of multi-component physical phase states accompanied by the observation of particle size change and morphology. We also studied the correlation between antibacterial activity and physical structure of phase states. The results showed during boiling process the degree of hybridization of particles was decreased and the particle size distribution was narrowed and stabilized at 170 nm. The distribution of organic and inorganic components was heterogeneous among different phase states. S-13500, supernatant isolated by 13 500×g centrifugation, constituted by ephedrine, amygdalin, glycyrrhizic acid and inorganic components Ca, K, Mg, etc., had the strongest antibacterial activity. The molecular interaction force in the active physical phase state was mainly hydrophobic and hydrogen bond. The destruction of the interaction force will lead to the change of phase structure and the decrease of antibacterial activity in vitro and in vivo. This study confirms that, in the boiling process of the Ma-Xing-Shi-Gan Decoction, the chemical components interweave and interact to form new physical phase states, leading to heterogeneous distribution of components. The antimicrobial activity of the active phase depends on both chemical composition and physical structure, which provides a direct evidence for the physical basis of the efficacy of traditional Chinese medicine.
Key words:    Ma-Xing-Shi-Gan Decoction    precipitation    phase state    physical structure    antibacterial    interaction mechanism    supermolecule    structural Chinese medicine   
收稿日期: 2021-06-16
DOI: 10.16438/j.0513-4870.2021-0885
基金项目: 中央本级重大增减支项目(2060302-1907-04);中国科协青年人才托举工程项目(2017QNRC001);江苏省高等学校自然科学研究重大项目(20KJA360004);江苏省六大人才高峰项目(SWYY-057);江苏省青蓝工程项目;中药制药过程新技术国家重点实验室开放基金(SKL2020Z0201);江苏省研究生科研创新工程项目(SJCX20_0564).
通讯作者: 乔宏志,Tel:86-25-85811050,E-mail:qiaohz@njucm.edu.cn;狄留庆,Tel:86-25-85811050,E-mail:diliuqing@njucm.edu.cn
Email: qiaohz@njucm.edu.cn;diliuqing@njucm.edu.cn
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