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Introduction: Panchakarma, the fivefold detoxification and rejuvenation therapy of Ayurveda, has been used for centuries to restore dosha balance and promote systemic health. In recent decades, attempts have been made to understand Panchakarma’s mechanisms using modern pharmacological and physiological concepts, highlighting its impact on neuroendocrine regulation, metabolism, immunity, and detoxification pathways. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, AYUSH Research Portal, and Google Scholar for studies published between 2000 and 2024. Search terms included “Panchakarma,” “Ayurveda,” “detoxification,” “pharmacology,” and “physiology.” Classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya) were reviewed to map traditional principles with modern biological correlates. Inclusion criteria comprised experimental, clinical, and review studies focusing on the physiological or pharmacological mechanisms of Panchakarma. Excluded were case reports, purely conceptual papers, and non-English publications. Results: Panchakarma interventions such as Vamana, Virechana, Basti, Nasya, and Raktamokshana demonstrate measurable effects on gastrointestinal motility, autonomic nervous system regulation, neuroendocrine balance, immune modulation, and metabolic detoxification. Clinical and experimental studies suggest reduction in inflammatory cytokines, improved gut microbiota balance, enhanced antioxidant defenses, and better hormonal regulation following Panchakarma. Discussion: Panchakarma aligns with modern pharmacological concepts of detoxification, immunomodulation, neuroendocrine regulation, and gut-brain axis modulation. However, mechanistic clarity is still evolving, and rigorous translational studies are required. Conclusion: Panchakarma offers an integrative therapeutic approach with plausible pharmacological and physiological underpinnings. Bridging Ayurvedic principles with modern science will strengthen its global relevance and evidence base.

KEYWORDS: Ayurveda, Detoxification, Immunomodulation, Panchakarma, Physiology