Advances in polyphenol-based strategies for musculoskeletal recovery and exercise rehabilitation in cancer: Mechanistic insights into Wnt/β-catenin and PI3K/Akt signaling pathways and inflammatory markers

Musculoskeletal dysfunction and compromised physical performance are prevalent complications observed in individuals diagnosed with cancer, frequently intensified by the administration of chemotherapy, radiotherapy, and extended periods of physical inactivity. Polyphenols (bioactive constituents derived from various plant sources) have exhibited significant anti-inflammatory, antioxidant, and anti-apoptotic characteristics that may serve to augment exercise interventions aimed at improving musculoskeletal recovery and rehabilitation outcomes. This review encapsulates the existing preclinical and clinical evidence regarding the synergistic effects of polyphenol supplementation in conjunction with structured exercise protocols in the context of cancer, with particular emphasis on underlying molecular mechanisms and functional outcomes. Prominent signaling pathways influenced by these combined therapeutic strategies include Wnt/β-catenin, PI3K/Akt, TNF-α/NF-κB, IL-4/STAT6, and TGF-β1/TRAF6, which are integral to the regulation of inflammation, apoptosis, muscle metabolism, and tissue remodeling. Preclinical investigations conducted using rodent cancer models consistently reveal that polyphenols such as curcumin, resveratrol, and genistein, significantly enhance the efficacy of both aerobic and resistance exercise concerning tumor suppression, muscle preservation, and modulation of molecular pathways. Clinical evidence, although scarce, suggests potential enhancements in muscular strength, endurance, and recovery when polyphenolic compounds are utilized in conjunction with exercise rehabilitation, particularly among individuals undergoing oncological treatment. Despite these encouraging results, variability in dosing regimens, formulations, timing, and participant demographics constrains the generalizability of the findings. Subsequent research endeavors should prioritize the development of standardized polyphenolic preparations, refined exercise protocols, and clinically relevant functional outcomes to establish evidence-based clinical guidelines. The integration of polyphenols with exercise represents an auspicious non-pharmacological approach to augment musculoskeletal function and enhance quality of life in the context of cancer rehabilitation.