Effect of vanillic acid on pentylenetetrazole-kindled rats: Nrf2/HO-1, IGF-1 signaling pathways cross talk

Abstract

Vanillic acid (VA) exhibited antioxidant and neuroprotective properties in some neurodegenerative disorders. So, the current study examined the neuroprotective potential of VA as an antiepileptic agent in pentylenetetrazole (PTZ)-induced epileptic rats and the prospective role of Insulin like growth factor-1 (IGF-1) and nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in this respect. Thirty male albino rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/Kg, i.p. every other day) for 14 days, and (3) PTZ + VA group: received PTZ and VA (50 mg/Kg daily for 2 weeks). The seizure score and latency were evaluated a ter PTZ injection. Also, the markers of oxidative stress (malondialdehyde (MDA), catalase, and reduced glutathione (GSH)), histopathological examination, the expression of glial fibrillary acidic protein (GFAP) (a marker of astrocytes) IGF-1, Nrf2, and HO-1 were assessed in the brain tissues by the end of the experiment. PTZ caused significant decrease in seizure latency and significant increase in seizure score by the end of the experiment (p < 0.01). This was associated with significant increase in MDA and GFAP with significant decrease in GSH, total antioxidant capacity (TAC) and IGF-1 in brain tissues compared to normal group (p < 0.01). On the other hand, treatment with VA caused significant attenuation in PTZ-induced seizures which was associated with significant improvement in oxidative stress markers and downregulation in GFAP and upregulation of Nrf2, HO-1 and IGF-1 in CA3 hippocampal region (p < 0.01). VA showed neuroprotective and anti-epileptic e fects against PTZ-induced epilepsy which probably might be due to its antioxidant properties and upregulation of Nrf2/HO-1 pathway and IGF-1.

Amomum subulatum mitigates experimental thoracic radiation-induced lung injury by regulating antioxidant status and inflammatory responses

“…, have been reported to mitigate oxidative stress by activating the Keap1/Nrf2/ARE signalling axis. Ferulic acid, 35 alpinetin, 36 genistein, 37 vanillic acid, 38 epicatechin, 39 etc. are some of the bioactive polyphenols in MEAS that were reported to regulate the keap1/Nrf2 system.…”

Cardioprotective potential of vanillic acid

“…In addition, the anti-angiogenic effects of VA resulted in reduced expression of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) as well as cell G1 phase arrest. 69 The results of a recent study demonstrated that glial fibrillary acidic protein (GFAP) expression, as an indicator of astrocytosis, and neuronal loss were meaningfully reduced in epileptic rats after administration of VA. 75 Astrocytosis is associated with hyperexcitability due to downregulating glutamine synthase, which leads to increased unmetabolized glutamate and subsequent overproduction of free radicals. 75,76 Their study suggested that VA, through its antioxidant properties, modifies OS markers and upregulates nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signalling pathway and insulin-like growth factor 1 (IGF-1).…”

“…69 The results of a recent study demonstrated that glial fibrillary acidic protein (GFAP) expression, as an indicator of astrocytosis, and neuronal loss were meaningfully reduced in epileptic rats after administration of VA. 75 Astrocytosis is associated with hyperexcitability due to downregulating glutamine synthase, which leads to increased unmetabolized glutamate and subsequent overproduction of free radicals. 75,76 Their study suggested that VA, through its antioxidant properties, modifies OS markers and upregulates nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signalling pathway and insulin-like growth factor 1 (IGF-1). 75 In a major advance in 2021, Ahmadi and co-workers demonstrated that treatment of β-amyloid (Aβ) peptide-treated rats with VA ameliorates learning and memory function, enhances total antioxidant capacity (TAC) and total oxidant status (TOS), and diminishes malondialdehyde (MDA) level through inhibiting OS.…”

“…75,76 Their study suggested that VA, through its antioxidant properties, modifies OS markers and upregulates nuclear factor-2 erythroid-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signalling pathway and insulin-like growth factor 1 (IGF-1). 75 In a major advance in 2021, Ahmadi and co-workers demonstrated that treatment of β-amyloid (Aβ) peptide-treated rats with VA ameliorates learning and memory function, enhances total antioxidant capacity (TAC) and total oxidant status (TOS), and diminishes malondialdehyde (MDA) level through inhibiting OS. 77 The increased Nrf2 expression is one of the mechanisms contributing to the memory-enhancing effects of VA against Aβ.…”

“…The results of a recent study demonstrated that glial fibrillary acidic protein (GFAP) expression, as an indicator of astrocytosis, and neuronal loss were meaningfully reduced in epileptic rats after administration of VA 75 . Astrocytosis is associated with hyperexcitability due to down‐regulating glutamine synthase, which leads to increased unmetabolized glutamate and subsequent overproduction of free radicals 75,76 .…”