Abstract: Objective To study the mechanisms by which ginseng combined with Radix Aconiti Carmichaeli can reduce toxicity while improving efficacy in terms of chemistry, pharmacokinetics, drug metabolism, interactions between components and biological mechanisms. Methods The “dose- toxicity-time-effect” relationship was established based on drug dosage and molecular pathways. Energy metabolism and calcium overload were studied to find out whether they were involved in pharmacological and toxic effects, respectively. The toxicity conversion window of aconitine was analyzed while the toxicity threshold was predicted using physiologically based pharmacokinetic models (PBPK) and in vivo reverse dosimetry. The early toxicity dose of traditional Chinese medicine, impacts of drug metabolic enzymes and transporters on the in vivo disposal process of drugs, and drug interactions were explored. Results It was found that the combination of ginseng with Radix Aconiti Carmichaeli could reduce the concentration of aconitine through pharmacological mechanisms and antagonize toxic targets through toxicological mechanisms, thus acting as both a threat and a killer in the compatibility theory of “seven emotions and harmony”. Conclusion The study has shed light on the role of ginseng combined with Radix Aconiti Carmichaeli in reducing toxicity and increasing efficiency, and contributed to the compatibility theory about the “seven emotions and harmony”.

Key words: combination of ginseng and Radix Aconiti Carmichaeli, reduction of toxicity and increase of efficiency, aconitine, myocardial cells, drug metabolism enzyme, seven emotions and harmony