Pathway enrichment and network pharmacology identify convergent mechanisms of Renew® bioactive components across...

Alterations of physiological processes, including nervous system activity, sleep regulation, fatigue response, pain perception, immune function and cognitive performance, present a growing global health concern, underscoring the need for strategies capable of modulating interconnected biological networks. Multi-component formulations combining distinct bioactive molecules offer potential systemic benefits, however their common molecular mechanisms, including potential cooperative interactions, remain poorly defined. This study aims to explore how the bioactive component of Renew® (alpha-glycerophosphorylcholine, magnesium bisglycinate and L-5-methyltetrahydrofolate) converge on shared protein interaction networks linked to multiple physiological domains. Protein-Protein interaction networks were constructed for each component and merged with condition-specific interactomes, followed by a path-based filtering strategy utilizing a maximum of four intermediaries to identify convergent molecular paths supported by multiple Renew® components. It is worth noting that the filtering reduced thousands of interactions to a very compact core in which all the paths with multiple conditions that were retained originated from just eight Renew® targets and converged on 22 condition-associated outputs. Functional enrichment analysis of retained proteins revealed significant convergence on pathways including EGFR/ErbB signaling, long-term potentiation, one-carbon metabolism, folate biosynthesis, and longevity regulation. The most consistently represented protein sets within the retained paths were those annotated with cell growth, immune system regulation, nervous system function and pain ontologies, with choline-associated targets emerging as central hubs. While mapping out a potential mechanistic framework, these in silico results identify a restricted set of strategic nodes through which Renew® bioactive components potentially influence plasticity, tissue regeneration and metabolic homeostasis. This integrative approach provides a computational basis for generating biological hypotheses that can be used to guide future experimental validation and the rational design of nutraceuticals.