Song Shuai, Ma Qinhai, Tang Qingfa, Chen Feilong, Xing Xuefeng, Guo Yang, Guo Shenshen, Tan Xiaomei, Luo Jiabo
School of Traditional Chinese Medical Science, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China.
Department of Pharmacy, The Renhe Affiliated Hospital to China Three Gorges University, Yichang 443002, PR China.
J Ethnopharmacol. 2016 Feb 17;179:356-66. doi: 10.1016/j.jep.2015.12.019. Epub 2015 Dec 21.
The Mahuang-Xingren (MX) herb pair, the combination of Herba Ephedrae (Mahuang in Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a core component of traditional Chinese medicine formulations used to treat asthma and bronchitis. Although Xingren is considered to be toxic, MX is widely used in the clinic and has few adverse effects. The mechanism underlying detoxification of Xingren by Mahuang in MX remains unknown and merits investigation.
To determine the mechanism underlying detoxification of Xingren by Mahuang in MX.
Acute toxic effects were evaluated in mice after oral administration of Mahuang, Xingren, and MX aqueous extracts. Synergism, additivity, and antagonism were quantified by determining the CI (combination index) and DRI (dose-reduction index), which were calculated by the median effect method. High performance liquid chromatography analysis of bioactive compounds (ephedrine, pseudoephedrine and amygdalin) in aqueous extracts and data from previous pharmacokinetic studies in rats were combined to explore the potential mechanism of toxicity antagonism by the components of MX. Moreover, the cytotoxic effects of amygdalin and amygdalin activated by β-glucosidase (including different proportions of l-amygdalin and d-amygdalin) were also investigated.
Mahuang prevented and antagonized the acute toxicity of Xingren and allowed escalation of the Xingren dose. Pearson correlation analysis indicated that the proportion of d-amygdalin was closely correlated with the antagonism of Xingren toxicity. The antagonism of its acute toxicity was primarily attributed to stereoselective metabolism of amygdalin. Interestingly, the process was facilitated by Mahuang, which led to reduced levels of the d-prunasin in vivo and thus reduced toxicity. Furthermore, the mechanism was also evaluated by testing the cytotoxicity of amygdalin. Metabolism of d-amygdalin was a major cause of cytotoxicity and no stereoselective metabolism occurred in culture medium.
A comprehensive study of Xingren detoxification in the context of the MX combination suggested that stereoselective metabolism of amygdalin facilitated by Mahuang may be the crucial mechanism underlying detoxification of Xingren in the MX combination. Therefore, Mahuang acts to enhance and control the effects of Xingren in the MX combination. These results illustrate the rationale behind the combination of Mahuang and Xingren.
麻黄-杏仁药对，即麻黄（Herba Ephedrae，中药名为麻黄）与苦杏仁（Semen Armeniacae Amarum，中药名为杏仁）的组合，是用于治疗哮喘和支气管炎的中药方剂的核心成分。尽管杏仁被认为有毒，但麻黄-杏仁药对在临床上广泛使用且不良反应较少。麻黄-杏仁药对中麻黄对杏仁的解毒机制尚不清楚，值得研究。
确定麻黄-杏仁药对中麻黄对杏仁的解毒机制。
给小鼠口服麻黄、杏仁及麻黄-杏仁药对水提取物后评估急性毒性作用。通过测定CI（联合指数）和DRI（剂量降低指数）来量化协同作用、相加作用和拮抗作用，CI和DRI通过中位效应法计算得出。将水提取物中生物活性成分（麻黄碱、伪麻黄碱和苦杏仁苷）的高效液相色谱分析结果与先前大鼠体内药代动力学研究数据相结合，以探索麻黄-杏仁药对各成分的毒性拮抗潜在机制。此外，还研究了苦杏仁苷以及经β-葡萄糖苷酶激活的苦杏仁苷（包括不同比例的l-苦杏仁苷和d-苦杏仁苷）的细胞毒性作用。
麻黄预防并拮抗了杏仁的急性毒性，使杏仁剂量得以增加。Pearson相关性分析表明，d-苦杏仁苷的比例与杏仁毒性的拮抗作用密切相关。其急性毒性的拮抗作用主要归因于苦杏仁苷的立体选择性代谢。有趣的是，麻黄促进了这一过程，导致体内d-扁桃苷水平降低从而降低了毒性。此外，还通过检测苦杏仁苷的细胞毒性来评估该机制。d-苦杏仁苷的代谢是细胞毒性的主要原因，且在培养基中未发生立体选择性代谢。
在麻黄-杏仁药对背景下对杏仁解毒进行的综合研究表明，麻黄促进的苦杏仁苷立体选择性代谢可能是麻黄-杏仁药对中杏仁解毒的关键机制。因此，麻黄在麻黄-杏仁药对中起到增强并控制杏仁作用的效果。这些结果阐明了麻黄与杏仁配伍的原理。
