Curcumin and piperine in neurodegenerative disorders: a systematic review of preclinical neuroprotective evidence

Background: Curcumin and piperine are phytochemicals with neuroprotective potential; however, curcumin's limited bioavailability restricts its therapeutic efficacy. Increasing evidence suggests that their co-administration may provide synergistic neuroprotective benefits. This systematic review evaluates the current preclinical evidence for curcumin-piperine (CUR-PP) combinations in neurodegenerative disorder models. Methods: We searched electronic databases for studies published between 2010 and 2026. Twenty unique preclinical studies, involving rodent models and neuronal cell cultures, met the eligibility criteria. Due to substantial methodological heterogeneity in study designs, dosing regimens, and outcome measures, a quantitative meta-analysis was not feasible. Findings were synthesized qualitatively, focusing on behavioral, biochemical, and molecular outcomes. Results: CUR-PP co-administration consistently demonstrated superior neuroprotective efficacy compared to monotherapy. The combination significantly improved cognitive and locomotor performance, mitigated oxidative stress, and modulated neuroinflammatory pathways. Nanoformulations, such as PLGA nanoparticles, further enhanced bioavailability and therapeutic impact across the included studies. Conclusion: Preclinical data indicate that CUR-PP combinations exert synergistic neuroprotective effects, suggesting they are promising multi-target candidates for neurodegeneration. However, the therapeutic potential is currently limited by a reliance on preclinical models, substantial inter-study heterogeneity, and a total lack of clinical trial data, which prevents the establishment of validated human dosing protocols.