Herbo-Mineral Medicine, Cardiogrit Gold, Exhibits Protective Effects in Caenorhabditis elegans Model of Doxorubicin-Induced Cardiotoxicity.

Doxorubicin, an effective antineoplastic agent, is often prescribed for the treatment of various carcinomas. However, the use of doxorubicin becomes limited due to its adverse effects like cardiotoxicity, dysmenorrhea, and leucopenia. Cardiogrit Gold (CG) is a herbo-mineral Ayurvedic medicine prescribed for the treatment of various cardiovascular ailments. The current study aimed to investigate the therapeutic potential of CG in imparting protection against doxorubicin-induced cardiotoxicity. Wild-type (N2) and genetically modified Caenorhabditis elegans(SJ4005 and DA597) were used as model organisms to assess the bioactivity of CG against doxorubicin-induced cardiotoxicity. Chemical characterization of CG was performed by HPLC-based analysis. Calcium, a key mineral component of CG, was measured in CG-treated C. elegans using inductively coupled plasma mass spectrometry (ICP-MS) analysis, as the marker of CG internalization in C. elegans. Toxicity induced by doxorubicin and its recovery upon CG treatment was determined by various toxicologically important endpoints. CG treatment rescued N2 C. elegans from doxorubicin-induced reduction in their growth, reproduction, locomotory behavior, pharyngeal pumping, feeding ability, and increased ROS generation. CG treatment modulated the expression of hsp-4 in SJ4005 C. elegans suggestive of decreased ER stress and normalized the pharyngeal grinder damage in DA597 C. elegans, indicating a robust induction of cardio-normalcy. Novel analytical methods were developed to detect and quantify doxorubicin in C. elegans on HPLC and UPLC/QToF-MS platforms. Interestingly, CG treatment decreased bioaccumulation of doxorubicin in C. elegans, robustly correlating with the observed cardioprotective effects. Taken together, CG has a strong cardioprotective profile against doxorubicin-induced damages and could be taken for further preclinical and clinical assessments.