Screening and Identification of Antipyretic Components in the Postfrost Leaves of Morus alba Based on Multivariable and Continuous-Index Spectrum-Effect Correlation

The leaves of Morus alba (LMA) are crucial traditional Chinese medicine (TCM) of clearing heat. In ancient Chinese materia medica and the current Pharmacopoeia of the People's Republic of China, LMA are recorded to be harvested after frost for medicinal purpose. However, the reason and mechanism of this traditional usage have been still unknown so far. In this work, it was confirmed firstly that the antipyretic effect of LMA after frost was better than that of before frost significantly on feverish rats. Subsequently, the chemical profiles of LMA before and after frost were characterized by fingerprint, respectively. Then, the endemic peaks after frost and positive differential peaks were screened as the research object of spectrum-effect correlation by orthogonal signal correction partial least square discrimination (OPLS). Finally, a multivariable and continuous-index spectrum-effect correlation model coupled with OPLS was established. As a result, the antipyretic components of postfrost LMA were screened and identified as citric acid derivative and tryptophan which may be the synergistic material basis. The study can provide a scientific foundation for the enhancement of effects in the postfrost LMA. Moreover, the strategy of this research could provide a valuable reference for revealing the material basis of synergetic or antagonistic effects among other complex drug systems.