Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach

Cyclophosphamide is a key component of numerous chemotherapeutic protocols, demonstrating broad-spectrum efficacy against various malignancies and non-cancerous conditions. This review examines CPM's metabolic pathways, therapeutic applications, and its resulting organ-specific toxicities. Despite its clinical benefits in treating nephrotic syndrome, encephalomyelitis, breast cancer, ovarian cancer, and other diseases, CPM is associated with significant adverse effects on the kidneys, liver, heart, lungs, and intestines. The discussion delves into the molecular mechanisms underlying these toxicities, highlighting dysregulation in key signaling pathways, including Nrf2, NF-κB, MAPK/ERK, and AKT. In addressing these challenges, recent studies have identified various herbal drugs and phytochemicals capable of mitigating CPM-induced toxicity. Notable compounds such as cinnamaldehyde, baicalin, quercetin, and curcumin have demonstrated protective effects. Integrating these herbal formulations with CPM therapy is proposed to enhance patient safety and treatment efficacy. This review underscores the influence of CPM on apoptosis and inflammation pathways, which lead to alterations in organ-specific biomarkers. Phytochemicals may exert protective effects by restoring disrupted signaling pathways and normalizing altered biomarkers. The compilation of phytochemicals presented in this review serves as a valuable resource for researchers exploring other herbal products with potential protective effects against CPM toxicity. A significant gap in the current literature is the lack of clinical trials evaluating phytochemicals that mitigate CPM toxicity in vivo. Rigorous clinical studies are necessary to establish the efficacy and safety of herbal formulations in cancer treatment. Such research will clarify the role of natural remedies in complementing conventional therapies, ultimately improving patient outcomes.