Cardioprotective effect of <italic>Saussurea involucrata</italic> injection against Doxorubicin-induced cardiotoxicity by network pharmacology analysis and experimental verification

Doxorubicin (Dox) is widely utilized in the clinical treatment of various cancers. Despite its efficacy, Dox induces numerous adverse effects in humans with significant cardiotoxicity, posing a major limitation to its use. <i>Saussurea involucrata</i> injection (SII), derived from <i>Saussurea involucrata</i>, exhibits notable anti-inflammatory and anti-oxidative stress properties. However, its potential protective effects against Dox-induced cardiotoxicity (DIC) remain unexplored. In this study, we investigate the ability of SII to mitigate DIC and elucidate the underlying mechanisms through experimental research and network pharmacology analysis. Results from both <i>in vitro</i> and <i>in vivo</i> experiments reveal that SII treatment significantly improves Dox-induced cardiac dysfunction, reducing pathological alterations and fibrosis in cardiomyocytes. Moreover, SII has cardioprotective effects by diminishing the inflammation, oxidative stress, and apoptosis triggered by Dox. Network pharmacological analysis further shows that SII downregulates P53 protein expression by activating the AKT/MDM2 signaling pathway, thus attenuating DIC. In conclusion, this study confirms that SII mitigates DIC through downregulation of the AKT/MDM2/P53 signaling pathway, suggesting a promising therapeutic strategy for alleviating DIC.