PENG Wei, WANG Lin, FU Chaomei, et al. Study on Toxicity-efficacy Dualism of Fuzi (附子) Regarding its Anti-heart Failure Effect and Cardiotoxicity: Based on Network Pharmacology[J]. Journal of Traditional Chinese Medicine2021, 62(6): 523-529.
PENG Wei, WANG Lin, FU Chaomei, et al. Study on Toxicity-efficacy Dualism of Fuzi (附子) Regarding its Anti-heart Failure Effect and Cardiotoxicity: Based on Network Pharmacology[J]. Journal of Traditional Chinese Medicine2021, 62(6): 523-529.DOI: 10.13288/j.11-2166/r.2021.06.013.
Objective To explore the toxicity-efficacy dualism of Fuzi(Radix Aconiti Lateralis Praeparata) by taking the anti-heart failure effect and cardiotoxicity as an example. Methods The chemical components of Fuzi were collected through TCMSP database and literature reports; the targets of components were predicted by Swiss Target Prediction database
and the targets of anti-heart failure effect and cardiotoxicity of Fuzi were screened by TTD
UniProt
ClinVar databases. After analyzing the KEGG pathways of efficacy targets and toxicity targets
we used Cytoscape 3.7.1 software to construct the biological network of "components anti-heart failure targets/cardiotoxicity targets pathways". Furthermore
animal experiment was carried out to verify the effect of Fuzi on the cardiac troponin T(cTnT) in the myocardial tissue of heart failure model rats compared to normal rats by ELISA method. Results The results showed that the efficacy network was composed of 66 components
43 targets and 10 pathways
including calcium signaling pathway
neuroactive ligand-receptor interaction
cyclic guanylate phosphate cyclic guanylate-dependent protein kinase(cGMP-PKG) signaling pathway
and dilated cardiomyopathy. The toxicity network was composed of 46 components
16 targets and one pathway
which was adrenergic signaling in cardiomyocytes. The efficacy network and toxicity network of Fuzi were highly overlapped in terms of component
target and pathway. Animal study showed that Fuzi significantly reduced the cTnT content in myocardial tissue of heart failure model rats
while increased the cTnT content in normal rats. Conclusion The dualism of toxicity-efficacy of Fuzi is the result of the synergistic action of multiple components
multiple targets and multiple steps. The toxicity and efficacy network of Fuzi show high similarity in composition
target and pathway. The cardiotonic effect of Fuzi as an anti-heart failure herb is the cause of its cardiac toxicity
and the toxicity and efficacy of Fuzi are closely related.