Rehmannioside A alleviates neuroinflammation and cognitive impairments after traumatic brain injury by suppressing microglial activation via the MAPK/NF-κB pathway.

BACKGROUND

Traumatic brain injury (TBI) triggers a robust neuroinflammatory response characterized by microglial activation, which propagates secondary neuronal damage and contributes to long-term neurological deficits. Rehmannioside A (REA), a principal bioactive compound from Rehmannia glutinosa, has emerged as a candidate for neuroprotection due to its anti-inflammatory properties. However, its therapeutic potential and precise mechanisms of action in TBI remain to be fully elucidated.

METHODS

We employed a controlled cortical impact (CCI) model in mice to mimic clinical TBI. Animals were randomized into Sham/Veh, Sham/REA, TBI/Veh, and TBI/REA (40 mg/kg) groups. Neurological and cognitive functions were assessed using the modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM). Cerebral edema was measured, and histopathological changes were evaluated by H&E and Nissl staining. LPS-stimulated BV2 microglial cells were used for in vitro experiments. Pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and qRT-PCR, and activation of the MAPK/NF-κB pathway was analyzed by western blotting.

RESULTS

REA treatment significantly improved neurological scores, spatial learning and memory, and reduced cerebral edema and neuronal loss in TBI mice. REA suppressed microglial activation in vivo and dose-dependently inhibited LPS-induced pro-inflammatory mediators in vitro. These beneficial effects are associated with reduced phosphorylation of p65 (NF-κB) and p38 (MAPK) in activated microglia in vitro.

CONCLUSION

REA ameliorates functional deficits and neuropathology following TBI. The neuroprotective effect may involve suppression of microglia-mediated neuroinflammation via inhibition of the MAPK/NF-κB signaling pathway.