Quantitatively analyze composition principle of Ma Huang Tang by structural equation modeling

In Chinese classic formulas, Ma Huang Tang (MHT), composed of Ephedra, Cassia twig, Bitter apricot kernel and Prepared licorice, has been widely used to treat cold, influenza, acute bronchitis, bronchial asthma and other pulmonary diseases. However, there is no quantitative interpretation about composition principle of MHT as well as other Chinese compound prescriptions. This study was aimed using structural equation modeling (SEM) to decipher 'monarch, minister, assistant and guide' which is the unique and integrated composition principle of Chinese compound recipes, by taking MHT for instance.Sixteen prescriptions of different dose ratios were combined orthogonally from four herbal drugs of MHT, then their diaphoretic, antispasmodic and analgesic effects were assessed by the indicators of the rat sweating point number, the spasmolysis percentage of guinea pig trachea and the murine writhing number, respectively. Basing on SME, the systematology analysis method to complex causality, path diagrams for herbal drugs were drawn with the Amos software and the relationships of the four herbal ingredients and therapeutic effects were measured.Sixteen recipes induced SD rats sweating, remitted spasm of guinea pig trachea smooth muscle, and relieved ICR mouse pain due to acetic acid in comparison with animal model group or normal control groups. Three different SME models were specified and the relevant relationship was analyzed. According to the results of measured standardized path coefficients, Ephedra exerts the greatest contribution to the integral potency, so it acts as the monarch drug in MHT; Cassia twig is slightly weakly effective than Ephedra, and has the most significant interaction with Ephedra, which shows that it is the minister drug; the direct effects of Bitter apricot kernel and Prepared licorice on the integral potency are non-significant, while these two drugs have very significant synergetic effect with Ephedra or Cassia twig, thus they can be interpreted as subordinate drugs to strengthen the therapeutical effects of the monarch and minister drugs; the higher interaction values of Bitter apricot kernel suggest that it is the assistant drug, and Prepared licorice is the guide drug with lower values.SME can be used to quantitatively analyze the composition principle of Chinese compound prescriptions like MHT, which demystifies the ancient and classical system theory of traditional Chinese medicine from a totally new viewpoint.