Your review outlines a wide spectrum of plant-derived secondary bioactive metabolites (SBMs) such as polyphenols, terpenoids, and PUFAs, highlighting their potential as “theravention” agents against neurodegenerative disorders (NDDs). While the paper compiles a good array of in vitro assays, animal models, and mechanistic insights, there appears to be a significant disconnect between the preclinical promise and clinical applicability. Many of the cited studies rely heavily on non-physiological concentrations of SBMs, use simplified cellular models, or involve animal dosing regimens that are neither translatable nor sustainable in human diets or supplement form. Moreover, issues like poor oral bioavailability, rapid metabolism, low systemic stability, and variable gut microbiota interaction are acknowledged briefly but not rigorously analyzed in your conclusion.
Given this, how can the review justify strong claims about the preventive or therapeutic potential of SBMs for NDDs when the translational pipeline remains largely speculative and unsupported by robust, long-term clinical trials with cognitive endpoints? Wouldn’t it be more scientifically sound to emphasize these translational barriers rather than extrapolate preclinical efficacy to potential human benefit without firm pharmacokinetic or pharmacodynamic grounding?