Oxyberberine protects middle cerebral artery occlusion triggered cerebral injury through TLR4/NLRP3 pathway in rats

J Chem Neuroanat. 2024 Mar:136:102393. doi: 10.1016/j.jchemneu.2024.102393. Epub 2024 Jan 19.

Abstract

Cerebral ischemia is a life-threatening health concern that leads to severe neurological complications and fatalities worldwide. Although timely intervention with clot-removing agents curtails serious post-stroke neurological dysfunctions, no effective neuroprotective intervention is available for addressing post-recanalization neuroinflammation. Herein, for the first time we studied the effect of oxyberberine (OBB), a derivative of berberine, on transient middle cerebral artery occlusion (MCAO)-generated neurological consequences in Sprague-Dawley rats. The MCAO-operated rats exhibited significant somatosensory and sensorimotor dysfunctions in adhesive removal, foot fault, paw whisker, and rotarod assays at 1 and 3 days post-surgery. These MCAO-generated neurological deficits were prevented in OBB-treated (50 and 100 mg/kg) rats, and also coincided with a smaller infarct area (in 2,3,5-triphenyl tetrazolium chloride staining) and decreased neuronal death (in cresyl violet staining) in the ipsilateral hemisphere of these animals. The immunostaining of neuronal nuclear protein (NeuN) and glial-fibrillary acidic protein (GFAP) also echoes the neuroprotective nature of OBB. The increased expression of neuroinflammatory and blood-brain barrier tight junction proteins like toll-like receptor 4 (TLR4), TRAF-6, nuclear factor kappa B (NF-κB), pNF-κB, nNOS, ASC, and IKBα in the ipsilateral part of MCAO-operated rats were restored to normal following OBB treatment. We also observed the decline in plasma levels/mRNA transcription of TNF-α, IL-1β, NLRP3, IL-6, and matrix metalloproteinase-9 and increased expression of occludin and claudin in OBB-treated rats. These outcomes imply that OBB may prevent the MCAO-induced neurological consequences and neuroinflammation by interfering with TLR4 and NLRP3 signaling in rats.

Keywords: MCAO; NLRP3; Neuroinflammation; Oxyberberine; Stroke; TLR-4.

MeSH terms

  • Animals
  • Brain Injuries*
  • Brain Ischemia*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neuroinflammatory Diseases
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 4 / metabolism

Substances

  • Toll-Like Receptor 4
  • NLR Family, Pyrin Domain-Containing 3 Protein