Ayurvedic Phytochemicals in Oncology: ADP-Ribosylation as a Molecular Nexus

Cancer remains one of the most pressing health challenges of the 21st century, with rising global incidence underscoring the need for innovative therapeutic strategies. Despite significant advances in biotechnology, curative outcomes remain limited, prompting interest in integrative approaches. Ayurveda, the traditional Indian system of medicine, suggests a holistic therapeutic framework that is now gaining molecular validation in oncology. In this review, the literature was systematically collected and analyzed from major databases, including PubMed, Scopus, and Web of Science, encompassing studies across ethnopharmacology, biochemistry, and cancer biology. The analysis focused on Ayurvedic phytochemicals that modulate ADP-ribosylation (ADPr), a dynamic post-translational modification central to DNA repair, chromatin organization, and cellular stress responses, with particular emphasis on poly (ADP-ribose) polymerase (PARP)-mediated pathways and their oncological relevance. We have also explored the role of p53, a key stress-response regulator intricately linked to ADPr dynamics, which acts as a downstream effector integrating these molecular events with cell fate decisions. Evidence indicates that several Ayurvedic compounds, including curcumin, resveratrol, and withaferin A, influence PARP-p53 signaling networks, thereby modulating DNA repair fidelity, apoptosis, and tumor adaptation. The review further addresses challenges related to the poor solubility of these phytochemicals and highlights recent advances in Phyto-nanomedicine-based delivery systems that enhance their stability and therapeutic efficacy. Overall, the synthesis of Ayurvedic pharmacology with molecular oncology reveals mechanistic insights that may inform the rational development of novel, mechanism-driven cancer therapeutics.