Unveiling Active Constituents and Potential Targets Related to the Hematinic Effect of Steamed Panax notoginseng Using Network Pharmacology Coupled With Multivariate Data Analyses

Steamed Panax notoginseng (SPN) has been used as a tonic to improve the blood deficiency syndrome (BDS) in the theory of traditional Chinese medicine. Here, we aim to unveil active constituents and potential targets related to the hematinic effect of SPN, which has not been answered before. In the study a constituent-target-disease network was constructed by combining the SPN-specific and anemia-specific target proteins with protein-protein interactions. And the network pharmacology was used to screen out the underlying targets and mechanisms of SPN treating anemia. Also, the multivariate data analyses were performed for the double screening. According to the results, 11 targets related to chemical constituents of SPN were found to be closely associated with the hematinic effect of SPN. Among them, the direct target protein of mitochondrial ferrochelatase (FECH) had the major role through the metabolic pathway. Meanwhile, Rk(3) and 20(S)-Rg(3) were predicted to be major constituents related to the hematinic effect of SPN by both multivariate data analyses and network pharmacology. And it was been validated by the pharmacologic tests that Rk(3) and 20(S)-Rg(3) could significantly increase the levels of blood routine parameters, FECH and its downstream protein of heme in mice with BDS. The study provides evidences for the mechanism understanding and drug development of SPN for the treatment of anemia.