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Mechanism of Action of Natural Compounds in Peripheral Multiorgan Dysfunction and Hippocampal Neuroinflammation Induced by Sepsis

Summary

This research investigated how the medicinal mushroom Coriolus versicolor could help prevent brain damage and cognitive decline caused by severe infections (sepsis). The study found that this natural compound could both reduce immediate infection severity and prevent long-term brain inflammation and dysfunction. Impacts on everyday life: • Offers a potential natural treatment option for preventing cognitive decline after severe infections • Demonstrates how traditional medicinal mushrooms might help protect brain health • Provides new understanding of how infections can lead to long-term brain problems • Suggests possible preventive strategies for reducing dementia risk after serious illness • Shows promise for developing new therapies using natural compounds

Background

Bacterial sepsis induces excessive pro-inflammatory cytokines and oxidative stress, resulting in tissue injury and hyperinflammation. Patients recovering from sepsis have increased rates of central nervous system morbidities linked to long-term cognitive impairment and neurodegenerative pathologies. The molecular mechanisms connecting systemic inflammation to brain diseases need better understanding to develop new therapeutic strategies.

Objective

To evaluate the effects of Coriolus versicolor administration as a novel approach to treat polymicrobial sepsis and its impact on acute inflammation and long-term development of neuroinflammation and brain dysfunction triggered by chronic inflammation.

Results

Coriolus versicolor increased survival and reduced acute tissue injury by decreasing pro-inflammatory cytokines in bloodstream. In the hippocampus, it restored tight junction expressions, reduced cytokine accumulation and glia activation. It decreased TLR4, nNOS and NLRP3 inflammasome components expression. The treatment showed antioxidant activities by restoring GSH levels and enzyme activities while reducing oxidative stress markers. It also reduced AD-like pathology markers including APP, p-Tau, PHF1, AT8, IFITM3 expression and β-amyloid accumulation. Behavioral analyses showed improved cognitive function and synaptic plasticity.

Conclusion

Coriolus versicolor administration effectively counteracted both the acute phase of sepsis and chronic neurodegenerative processes. It significantly reduced microglia and astroglia activation, amyloid-beta deposition, and associated cognitive dysfunctions, demonstrating potential as a therapeutic approach for sepsis-induced neurodegeneration.
  • Published in:Antioxidants,
  • Study Type:Experimental Animal Study,
  • Source: 10.3390/antiox12030635
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