Stereoselectivity And Deamination Of Amygdalin In Mahuang-Xingren As A Metabolic Detoxification Mechanism

Mahuang-Xingren（MX,Ephedra sinica Stapf-Prunus armeniaca L.）is a classic herb pair used in traditional Chinese medicine and has the effect of relieving cough and asthma.Amygdalin is one of the main active components of Xingren,accounting for 3%of Xingren seeds.Amygdalin is sequentially metabolized into prunasin,mandelonitrile,and finally to hydrolyzed to benzaldehyde and hydrogen cyanide.However,the cyanogenesis metabolism pathway is a well-known mechanism for metabolic poisoning.Previous studies have found that compatibility of Mahuang can reduce the toxicity of Xingren,and Mahuang may play a key role in compatibility attenuation by affecting the stereoselective metabolism of amygdalin.Whether the effect of Mahuang on the stereoselective pharmacokinetics of amygdalin is important in both traditional decoction and formula granules is unknown.The metabolism of amygdalin into cyanogen hydride produces toxicity,so a comprehensive study of the metabolic pathways of amygdalin is essential to better understand the detoxification process.In this paper,the key role of stereoselective pharmacokinetics of amygdalin in compatibility attenuation was studied,and its results in traditional decoction and formula granules were also analyzed.In addition,it’s exploring the possible detoxification pathway of amygdalin.The experiment was divided into three parts:（1）Rats were intragastrical administered with Xingren decoction,MX decoction,Xingren formula granules and MX formula granules.Plasma was taken on time to detect plasma concentrations and compare the pharmacokinetics parameters of amygdalin and prunasin.（2）The effects of compatibility on the absorption of amygdalin were investigated by using different ratios of amygdalin and Xingren and MX through Caco-2 and MDCK cell monolayer models,while the traditional decoction and formula granules were compared and analyzed.（3）amygdalin was incubated with liver microsomes or gut microbial enzymes,and metabolites in the incubation system were detected and identified by high-resolution mass spectrometry.（1）The results showed that the combination of MX could relatively reduce the exposure of D-amygdalin in vivo and exert its detoxifying effect.This process could be further promoted in traditional decoction.（2）The cell experiments showed that compatibility of Mahuang could also promote the transport and absorption of D-amygdalin,and its absorption in the decoction was higher than that in the formula granules.（3）In the incubation system,a total of 15 metabolites of amygdalin were identified,which were divided into the cyanogenic pathway and the non-cyanogenic pathway.Some of metabolites were first proposed in this study.In summary,the attenuation effect of MX may be a common result in vivo and in vitro,the stereoselectivity and deamination metabolism of amygdalin are its detoxification pathways.MX decoction cannot be replaced by its formula granules.