Title:Network Pharmacology along with Molecular Docking to Explore the Mechanism of
Danshen Injection against Anthracycline-induced Cardiotoxicity and Transcriptome
Validation
Volume: 30
Issue: 12
Author(s): Quankai Dai, Yijun Pan, Xiwen Zhu, Mengyao Chen, Lin Xie, Yu Zhu and Guoxing Wan*
Affiliation:
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China
Keywords:
Danshen injection, anthracycline-induced cardiotoxicity, network pharmacology, transcriptome sequencing, molecular docking, cardioprotection.
Abstract:
Introduction: Although anthracyclines have demonstrated efficacy in cancer therapy, their utilization
is constrained by cardiotoxicity. In contrast, Danshen injection (DSI), derived from Salvia miltiorrhiza,
has a longstanding tradition of being employed to ameliorate cardiovascular ailments, including anthracycline-
induced cardiotoxicity (AIC). Nonetheless, there is a notable dearth of comprehensive systematic investigation
into the molecular mechanisms underlying DSI's effects on AIC. Consequently, this study was undertaken
to explore the underlying mechanism by which DSI acted against AIC.
Methods: Employing network pharmacology approach, the current investigation undertook a comprehensive
analysis of the impact of DSI on AIC, which was further validated by transcriptome sequencing with in vitro
AIC model. Additionally, molecular docking was conducted to evaluate the binding of active ingredients to
core targets. A total of 3,404 AIC-related targets and 12 active ingredients in DSI, including chrysophanol,
luteolin, tanshinone IIA, isoimperatorin, among others, were collected by differentially expressed analysis and
database search, respectively.
Results: The network pharmacology and enrichment analysis suggested 102 potential targets and 29 signaling
pathways associated with the protective effect of DSI on AIC. Three core targets (CA12, NOS3, and POLH)
and calcium signaling pathways were further validated by transcriptomic analysis of the in-vitro model. The
high affinity of the active ingredients binding to corresponding targets was confirmed by molecular docking.
Conclusion: The present study suggested that DSI might exert a cardioprotective effect on AIC via the inhibition
of CA12, NOS3, and POLH, as well as the modulation of calcium signaling. Further experiments are
warranted to verify the findings.
