Development of models for classification of action between heat-clearing herbs and blood-activating stasis-resolving herbs based on theory of traditional Chinese medicine.

Background: Action (" gongxiao " in Chinese) of traditional Chinese medicine (TCM) is the high recapitulation for therapeutic and health-preserving effects under the guidance of TCM theory. TCM-defined herbal properties (" yaoxing " in Chinese) had been used in this research. TCM herbal property (TCM-HP) is the high generalization and summary for actions, both of which come from long-term effective clinical practice in two thousands of years in China. However, the specific relationship between TCM-HP and action of TCM is complex and unclear from a scientific perspective. The research about this is conducive to expound the connotation of TCM-HP theory and is of important significance for the development of the TCM-HP theory.

Methods: One hundred and thirty-three herbs including 88 heat-clearing herbs (HCHs) and 45 blood-activating stasis-resolving herbs (BAHRHs) were collected from reputable TCM literatures, and their corresponding TCM-HPs/actions information were collected from Chinese pharmacopoeia (2015 edition). The Kennard-Stone (K-S) algorithm was used to split 133 herbs into 100 calibration samples and 33 validation samples. Then, machine learning methods including supported vector machine (SVM), k-nearest neighbor (kNN) and deep learning methods including deep belief network (DBN), convolutional neutral network (CNN) were adopted to develop action classification models based on TCM-HP theory, respectively. In order to ensure robustness, these four classification methods were evaluated by using the method of tenfold cross validation and 20 external validation samples for prediction.

Results: As results, 72.7-100% of 33 validation samples including 17 HCHs and 16 BASRHs were correctly predicted by these four types of methods. Both of the DBN and CNN methods gave out the best results and their sensitivity, specificity, precision, accuracy were all 100.00%. Especially, the predicted results of external validation set showed that the performance of deep learning methods (DBN, CNN) were better than traditional machine learning methods (kNN, SVM) in terms of their sensitivity, specificity, precision, accuracy. Moreover, the distribution patterns of TCM-HPs of HCHs and BASRHs were also analyzed to detect the featured TCM-HPs of these two types of herbs. The result showed that the featured TCM-HPs of HCHs were cold, bitter, liver and stomach meridians entered, while those of BASRHs were warm, bitter and pungent, liver meridian entered.

Conclusions: The performance on validation set and external validation set of deep learning methods (DBN, CNN) were better than machine learning models (kNN, SVM) in sensitivity, specificity, precision, accuracy when predicting the actions of heat-clearing and blood-activating stasis-resolving based on TCM-HP theory. The deep learning classification methods owned better generalization ability and accuracy when predicting the actions of heat-clearing and blood-activating stasis-resolving based on TCM-HP theory. Besides, the methods of deep learning would help us to improve our understanding about the relationship between herbal property and action, as well as to enrich and develop the theory of TCM-HP scientifically.