Systems-level effects of plant-based cognitive enhancer extracts: A multi-omics perspective

Introduction

Plant-based cognitive enhancers act via multimodal neurobiological pathways and have demonstrated moderate efficacy in executive function in preclinical and clinical studies, with minimal occurrence of clinically adverse neurobehavior effects ^1–3. Among these, Centella asiatica is one of the most extensively investigated botanical extracts. While multi-omics tools are advancing our understanding of the metabolic profiling and biosynthetic pathways, systemic-level mechanisms and long-term safety remain incompletely mapped ⁴.

Aim and methodology

A systematic PRISMA-guided review was conducted in Scopus, and Web of Science to identify in vitro and in silico studies reporting transcriptomic and metabolomic analyses of plant-derived cognitive enhancers. A total of 38 studies met the inclusion criteria. Transcriptomic (RNA-seq and microarray) and metabolomic (LC-qTOF-MS and NMR) data were qualitatively synthesized. The following biological pathways were considered: neurotrophic signaling (BDNF and CREB), oxidative stress (Nrf2), inflammation (NF-κB), apoptosis, and energy metabolism.

Results

Evidence supports plant-based cognitive enhancers as polypharmacological, multitarget systems that over sustained dosing can upregulate BDNF and pathways associated with synaptic plasticity, modulate mitochondrial/Krebs cycle flux, enhance antioxidant responses, and influence inflammatory signaling pathways ^5–7. Recurrent transcriptomic and metabolomic signatures involved BDNF/CREB signaling, while C. asiatica-related studies reported positive and negative triterpene interactions with the neuronal transcriptome and metabolome of mouse cortical neurons ⁸. An integrated omics perspective could help resolve the networks of metabolites driving synergistic and antagonistic effects ⁹. Regardless of dose, standardization and diversity of the plant metabolomic pool, as well as rigorous long-term safety evaluations, remain essential for the responsible long-term use of these enhancers ^7,10.

Conclusions

The metabolic reprogramming and neuroprotective activities of plant-derived cognitive enhancers in the CNS are mechanistically complex and exhibit distinct multi-omics signatures. Integrating orthogonal analytical techniques, such as metabolomics and transcriptomics, may inform the rational design of safe and efficacious neuro-nutraceuticals for food applications.