Grape Seed Proanthocyanidins Exert a Neuroprotective Effect by Regulating Microglial M1/M2 Polarisation in Rats with Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.

Protection of Proanthocyanidins Against HSP Serum-Induced Inflammation and Oxidative Stress on Human Umbilical Vein Endothelial Cells

“…Results from our experiment showed that the protein and gene expressions of TLR4, MyD88 and NF-κB obviously elevated following HSP serum induction, which were consistent with the previous reports 7 , 8 , 10 and reconfirmed TLR4/MyD88/NF-κB pathway quite critical to HSP. Instead, the phosphorylated protein and mRNA levels of TLR4, MyD88 and NF-κB greatly dropped after intervention with different-concentration PCs; this outcome coincided with what was reported by Manna K and Wang, et al, 60–63 who demonstrated that PCs could reduce the expression of TLR4, MyD88 and NF-κB to inhibit inflammatory mediators release and deplete oxides, thereby curbing inflammation and OS. The current study, therefore, uncovered that PCs against experimental HSP was possibly through inhibiting the TLR4/MyD88/NF-κB pathway, TLR4 in particular.…”

Ferroptosis is a new therapeutic target for spinal cord injury

“…Proanthocyanidins (PACs), often extracted from grape seeds, are potent free radical scavengers ( Wang C. et al, 2022 ). PACs have been shown to promote recovery of motor function in rats with SCI ( Liu W. Z. et al, 2022 ). And in 2020 an investigator found that proanthocyanidins promote recovery of motor function in SCI mice by inhibiting Ferroptosis ( Zhou et al, 2020 ).…”

The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc

“…Microglial polarization may be regulated by the TLR4-mediated NF-B and PI3K/AKT signaling pathways. These in vivo investigations are based on Locomotor Recovery Assessment; Terminal Deoxynucleotidyl Transferase dUTP Nick-End Labeling (TUNEL) Assay; Annexin V-FITC/PI Assays; NO assay and immunofluorescence staining: NeuN, GFAP, CD86, CD206, p-NF-κB-p65, p-AKT [ 154 ].…”