Title:Mechanism Exploration of Astaxanthin in the Treatment of
Adriamycin-induced Cardiotoxicity based on Network Pharmacology
and Experimental Validation
Volume: 33
Issue: 1
Author(s): Yu Zhu, Mengyao Chen, Lin Xie, Yijun Pan, Yuntian Yang and Guoxing Wan*
Affiliation:
- Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
Keywords:
Astaxanthin, adriamycin-induced cardiotoxicity, network pharmacology, transcriptome sequencing, molecular docking, molecular dynamics simulations, cardioprotection.
Abstract:
Introduction: Astaxanthin (AXT), a natural antioxidant recognized for its
therapeutic potential in cancer and cardiovascular diseases, holds promise in mitigating
adriamycin-induced cardiotoxicity (AIC). Nevertheless, the underlying mechanisms of
AXT in AIC mitigation remain to be elucidated. Consequently, this study endeavors to
elucidate the mechanism of AXT against AIC, employing an integrated approach.
Methods: Network pharmacology, molecular docking, and molecular dynamics simulations
were harnessed to explore the molecular mechanism underlying AXT's action
against AIC. Furthermore, the in-vitro AIC model was established with the H9c2 cell to
generate transcriptome data for validation.
Results: A total of 533 putative AXT targets and 1478 AIC-related genes were initially
screened by database retrieval and bioinformatics analysis. A total of 248 potential targets
of AXT against AIC and several signaling pathways were identified by network
pharmacology and enrichment analysis. Two core genes (CCL2 and NOS3) and the
AGE-RAGE signaling pathway in diabetic complications were further highlighted by
transcriptome validation based on the AIC in-vitro model. Additionally, molecular docking
and dynamics analyses supported the robust binding affinity of AXT with the core
targets.
Conclusion: The study suggested that AXT might ameliorate AIC through the inhibition
of CCL2 and NOS3 as well as AGE-RAGE signaling, which provide a theoretical basis
for the development of a strategy against AIC.
