Korean black ginseng extract alleviates Alzheimer's disease-related cognitive impairment by activating the Nrf2/HO-1 pathway and suppressing the p38 MAPK/NF-κB/STAT3 pathways and NLRP3 inflammasome via TLR2 and TLR4 modulation

Abstract

Background

Korean black ginseng, a specially processed ginseng through repeat steaming and drying, has various pharmacological effects. However, its role in cognitive impairment remains unclear.

Purpose and methods

This study examined whether Korean black ginseng extract (BGE; 50 and 100 mg/kg, orally, 18 weeks) may mitigate cognitive impairment in a 5xFAD mouse model of Alzheimer's disease (AD).

Results

BGE significantly improved cognitive performance in 5xFAD mice, associated with reduced Aβ accumulation in the frontal cortex and hippocampus. BGE suppressed microglial and astrocytic activation, alongside the downregulation of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and enzymes (cyclooxygenase-2 and inducible nitric oxide synthase). These changes coincided with the inhibition of key inflammatory signaling pathways, such as p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB)/p65, signal transducer and activator of transcription (STAT) 3, and NOD-like receptor protein 3 (NLRP3) inflammasome. Furthermore, BGE reduced the generation of reactive oxygen species and enhanced the nuclear-E2-related factor 2 (Nrf2)-heme oxygenase 1 (HO-1) signaling pathway in the brains linked to the downregulation of toll-like receptors (TLR)-2 and TLR-4 in the brain.

Conclusion

Taken together, BGE could improve AD-related cognitive decline and neurodegeneration by simultaneously regulating anti-inflammatory pathways (p38 MAPK/NF-κB/STAT3 and NLRP3 inflammasome) and an antioxidant pathway (Nrf2/HO-1) via modulation of TLR2/4.