Phytochemical and Fungal Bioactive Compounds in the "Brain Health Triad": A Narrative Review on Neurostimulating, Neurotrophic, and Neuroprotective Synergy.

2026-04-18
International journal of molecular sciences 27(8)
- Giovanni Luca Cipriano
- Ivana Raffaele
- Alessia Floramo
- Veronica Argento
- Maria Francesca Astorino
- Maria Lui
- Marco Calabrò
- Ivan Anchesi

PubMed: 42074246
DOI: 10.3390/ijms27083607

Study Design

Type: Review

Rigorous Journal

This narrative review proposes the 'Brain Health Triad' as a novel integrative framework for neurorehabilitation and cognitive enhancement, built upon three interdependent biological pillars: neurostimulation, neurotrophy, and neuroprotection. We illustrate how the synergistic interplay between a 'core triad' composed of Hericium erinaceus, Bacopa monnieri, and L-Theanine targets these pillars with high specificity. Hericium erinaceus fosters neurotrophy by inducing Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) synthesis through erinacines and hericenones; Bacopa monnieri complements this by enhancing neurostimulation and synaptic plasticity via bacosides; and L-Theanine regulates neurotransmitter balance and alpha-wave activity to stabilize the neural signaling environment. This core architecture is further reinforced by adjunctive nootropic clusters-including withanolides, ginkgolides, citicoline, cordycepin, macamides, and fulvic acid-which provide essential support for mitochondrial resilience and the mitigation of amyloid-β and tau toxicities. By synthesizing molecular evidence from the BDNF/TrkB/CREB signaling axis and the Nrf2/NF-κB homeostatic switch, we demonstrate that this multi-target strategy offers a more robust path to neuronal resilience than traditional single-target approaches. We conclude that this integrated model provides a solid framework for future clinical applications in the management of age-related cognitive decline and neurodegenerative diseases.

Research Insights

Bacopa→Enhanced Synaptic Plasticity
Bacopa monnieri complements this by enhancing neurostimulation and synaptic plasticity via bacosides
Effect
Beneficial
Effect size
Moderate
Lion's Mane→Increased Brain-derived Neurotrophic Factor Level
Hericium erinaceus fosters neurotrophy by inducing Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) synthesis through erinacines and hericenones
Effect
Beneficial
Effect size
Moderate
Lion's Mane→Increased Nerve Growth Factor Level
Hericium erinaceus fosters neurotrophy by inducing Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) synthesis through erinacines and hericenones
Effect
Beneficial
Effect size
Moderate

Adverse Events Reported

Lion's Mane→Overall tolerability
The abstract does not report specific adverse events, side effects, or safety findings for Hericium erinaceus.
Finding
Reported
Bacopa→Overall tolerability
The abstract does not report specific adverse events, side effects, or safety findings for Bacopa monnieri.
Finding
Reported
L-Theanine→Overall tolerability
The abstract does not report specific adverse events, side effects, or safety findings for L-Theanine.
Finding
Reported