Bassia indica Attenuates Cardiotoxicity in a Rat Model via Anti-Inflammatory, Antioxidant, and Keap1/Nrf2 Modulation

<b>Background</b>: Drug-induced cardiotoxicity is a primary concern in clinical practice, especially in the context of oxidative stress induced by anti-cancer, antiviral, and antidiabetic drugs. Several strategies are devised to limit cardiotoxicity, which are supportive and provide symptomatic relief. This highlights the need to develop cardioprotective agents that circumvent the oxidative stress. <i>Bassia indica</i> is a cardiotonic plant with antioxidant properties traditionally used in Africa, South Asia, and China. We investigated its cardioprotective effects against doxorubicin-induced cardiotoxicity (DIC). <b>Methods</b>: <i>B. indica</i> extract (BiE) was analyzed by GC-MS and HPLC. Several antioxidant assays, including DPPH, FRAP, CUPRAC, NO, and H₂O₂ scavenging, were performed. In vivo attenuation of DIC was assessed in a rat model. <b>Results</b>: BiE contained several bioactive flavonoids, including 2-methoxy-4-vinylphenol, ferulic acid, gallic acid, kaempferol, and coumaric acid. Antioxidant assays demonstrated potent free-radical scavenging and antioxidant activity of BiE, providing mechanistic evidence for its in vivo amelioration of DIC. BiE treatment reduced myocardial oxidative stress by increasing endogenous antioxidant levels (<i>p</i> < 0.01), including SOD, CAT, and GSH. It upregulated Nrf2 and lowered Keap1 levels. This was also reflected in the restoration of cardiac tissue architecture and modulation of inflammatory markers, including IL-1β and TNF-α (<i>p</i> < 0.01). Cardiac tissue biomarkers were also improved. <b>Conclusions</b>: These findings conclude that BiE exerts cardiac protection by reducing oxidative stress and inflammation through modulation of the Keap1/Nrf2 pathway and decreasing the expression of IL-1β and TNF-α.