Abstract
Microglia polarization of classical activation state is crucial to the induction of neuroinflammation, and has been implicated in the pathogenesis of numerous neurodegenerative diseases. Fungal immunomodulatory proteins are emerging health-promoting natural substances with multiple pharmacological activities, including immunomodulation. Herein, we investigated the anti-inflammatory and neuroprotective potential of fungal immunomodulatory protein extracted from Ganoderma microsporum (GMI) in an in vitro rodent model of primary cultures. Using primary neuron/glia cultures consisting of neurons, astrocytes, and microglia, a GMI showed an alleviating effect on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced inflammatory mediator production and neuronal cell death. The events of neuroprotection caused by GMI were accompanied by the suppression of Nitric Oxide (NO), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), and Prostaglandin E2 (PGE2) production, along with the inhibition of microglia activation. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by GMI was accompanied by the resolution of oxidative stress, the preservation of protein tyrosine phosphatase and serine/threonine phosphatase activity, and the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein (CREB), along with signal transducers and activators of transcription (Stat1) transcriptional activities and associated upstream activators. These findings suggest that GMI may have considerable potential towards the treatment of neuroinflammation-mediated neurodegenerative diseases.
Highlights
Neuronal dysfunction and/or death are common events contributing to both acute and chronic neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and stroke
We found that the GMI immunomodulatory protein of Ganoderma microsporum displayed both anti-inflammatory and neuroprotective effects in in vitro cell models
Using rodent primary neuron/glia cultures consisting of neurons, astrocytes, and microglia, GMI proved to have an alleviating effect on LPS/IFN-γ-induced inflammatory mediator production and neuronal cell death
Summary
Neuronal dysfunction and/or death are common events contributing to both acute and chronic neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and stroke. Activation of resident glial cells, the microglia, along with the recruitment of peripheral leukocytes, and the overproduction of inflammatory mediators within the nervous system, form the basis of neuroinflammation. These neuroinflammatory responses are present in the vicinity of degenerating neurons, cerebrospinal fluids, and even systemic blood circulation [1,2,3]. The line of evidence indicates that peripheral inhibition of inflammatory responses brings about benefits in cases of neurodegenerative diseases [4,5]. The aforementioned phenomena underscore the feasibility of anti-inflammatory strategies in the prevention and therapeutic treatment against neurodegenerative diseases
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