Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats

Abstract

Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.

The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review

“…In addition to that, polymorphism in the genotype of the NF-κB promoter was linked to a lower risk of IAs [ 17 ]. Similar to clinical studies, experimental studies using different animal models showed the elevated mRNA expression, protein levels, and/or activation of NF-κB in IA tissue compared to normal control arteries ( Table 2 ) [ 8 , 20 , 23 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 40 , 43 ]. The animal experimental studies revealed that blocking NF-κB P50 expression and NF-κB activation reduced the incidence of IA formation ( Table 3 ) [ 8 , 40 ], while enhanced NF-κB activation was linked to increased IA formation ( Table 3 ) [ 11 ].…”

Single-cell transcriptome analysis reveals the cellular atlas of human intracranial aneurysm and highlights inflammation features associated with aneurysm rupture

“…Thus, the question at hand is which type of macrophage should be actually targeted. Active inflammatory response activity is a distinctive feature of macrophages leading to AVM and TAA rupture, which is closely associated with transcriptional activation of classical and non-classical NF-κB signaling pathway [54][55][56] . Indeed, we found that CCL3/CXCL3 macrophages associated with IA rupture were manifested as transcriptional activation of NF-κB.…”

Lowering propionic acid levels by regulating gut microbiota with ursodeoxycholic acid appears to regress autism symptoms: an animal study

“…Increased MDA and lactate levels and also decreased NGF and NRF2 levels are signs of acidosis and oxidative stress. 42 Today, there is strong evidence concerning the role of brain oxidative stress in the pathophysiology of autism. 43 Accordingly, we can theorize that UDCA treatment may ameliorate oxidative stress in the brain of autistic patients via regulation of gut microbiome.…”