Abstract
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, Rk3 and 20(S)-Rg3 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 Rk3 and 20(S)-Rg3 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.
Highlights
Blood deficiency syndrome (BDS) is a common syndrome with high incidence in clinic of traditional Chinese medicine (TCM), which often occurs in patients with anemia
The red triangles represented the analyzed constituents of steamed Panax notoginseng (SPN), the blue dots represented the indirect targets of those constituents, the yellow dots represented the targets of anemia, the purple dots represented the interactional proteins of the anemia targets and SPN constituents, and the yellow squares represented the common targets of SPN constituents and anemia
To unveil the bioactive constituents and investigate the action mechanism of SPN for improving BDS, the network pharmacology approach coupled with multivariate data analyses were performed
Summary
Blood deficiency syndrome (BDS) is a common syndrome with high incidence in clinic of traditional Chinese medicine (TCM), which often occurs in patients with anemia. It is characterized by a decreased quantity of red blood cells (RBC) and white blood cells (WBC), usually accompanied by the diminished hemoglobin (Hb) levels or altered RBC morphology (Kassebaum et al, 2014). Hemolytic anemia is mainly treated with blood transfusion This treatment is associated with mechanical shearing forces that accelerate red blood cell rupture, and lead to severe clinical complications, including intravascular hemolysis, tissue oxidative stress, and multi-organ dysfunctions (Baek et al, 2012). The development of effective therapies or drugs with blood-enriching efficacy is beneficial for the prevention and treatment of the disease
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