# Neuroprotective Potential of Hericium erinaceus Through Modulation of Inflammatory Signaling in THP-1 Macrophages Under Low-Level Lead Exposure

## TL;DR

This study explores how Hericium erinaceus may protect the brain by modulating inflammation in cells exposed to low levels of lead.

## Contribution

The novel finding is that HE modulates inflammatory signaling in macrophages under low lead exposure, suggesting a neuroprotective mechanism.

## Key findings

- HE exposure combined with low lead levels shifts cyclooxygenase expression toward COX-2 and increases PGE2 production.
- HE modulates inflammatory signaling rather than amplifying it in macrophages under low lead exposure.
- HE treatment fine-tunes MCP-1 secretion and alters macrophage morphology, indicating immunomodulatory effects.

## Abstract

Exposure to lead is associated with microglial dysfunction and the development of neuroinflammation. This contributes to accelerated neurodegeneration. Even low doses of this element modulate inflammatory responses and might contribute to central nervous system dysfunction. Extracts from the mushroom Hericium erinaceus (HE) possess well-documented neurotropic properties; however, its potential neuroprotective mechanisms under conditions of environmental neurotoxicity remain poorly defined. In this study, we investigated the effects of HE on inflammatory signaling in a microglia-oriented in vitro model using THP-1-derived macrophages exposed to low levels of lead (3.5 µg/dL). In our study, Pb exposure did not increase tumor necrosis factor (TNF) alpha levels but reduced monocyte chemoattractant protein-1 (MCP-1) secretion and altered cyclooxygenase (COX) expression, indicating immune response modulation rather than inflammatory activation. Under combined Pb and HE exposure, a marked shift in cyclooxygenase expression toward COX-2 at both the gene and protein levels was observed, accompanied by increased PGE2 production; these effects were dose-dependent. The inflammatory signaling was modulated rather than amplified. Also, TNF alpha levels were elevated after combined treatment, whereas gene expression responses were dose-dependent. MCP-1 secretion was fine-tuned toward control values, consistent with macrophage morphological changes, while IL-6 levels were increased. Overall, these findings indicate that Hericium erinaceus exerts immunomodulatory effects in microglia-like cells under low-level lead exposure, supporting its neuroprotective potential through modulation of neuroinflammatory signaling.