Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice

Abstract

The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

Vinpocetine and Ischemic Stroke

“…Neuronal mitochondrial reactive oxygen species (ROS) contribute into the pathogenesis of I/R injury in IS as well as neurodegeneration and glutamate excitotoxicity [40]. VPN activates peripheral benzodiazepine receptors (BBRs) which regulate mitochondrial outer cell membrane and prevent the opening of mitochondrial permeability transition pore (MPTP).…”

Role of vinpocetine in ischemic stroke and poststroke outcomes: A critical review

“…[44] Neuronal mitochondrial reactive oxygen species contribute to the pathogenesis of I/R injury in IS as well as neurodegeneration and glutamate excitotoxicity. [45] VPN activates peripheral benzodiazepine receptors which regulate mitochondrial outer cell membrane and prevent the opening of mitochondrial permeability transition pore (MPTP). Furthermore, VPN prevents mitochondrial dysfunction through prevention of mitochondrial depolarization, inhibition of mitochondrial Na + /Ca 2+ exchange, anticipation of mitochondrial Ca 2+ release, MPTP opening, and the release of free radicals from outer mitochondrial membrane during neuronal injury.…”

Phosphodiesterase Inhibitors for Alzheimer’s Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale

“…Discovered in the 1970s by C. Szántay and C. Lörincz et al independently, vinpocetine has been approved in European countries for the treatment of dementia and stroke for over 30 years, and it is available in the United States as a dietary supplement [225]. Preclinical data demonstrate that vinpocetine can rescue cognitive deficits in a rodent AD model [226], increase CREB phosphorylation [227] and BDNF expression [228], downregulate BACE1 [226], upregulate Nrf2 mRNA expression [229], decrease oxidative stress [226,[228][229][230][231][232][233][234][235][236][237][238][239], mitochondrial dysfunction [240,241], and apoptosis [230,239], inhibit GSK3␤ [226,228], NFκB [229,231,232,239,[242][243][244][245][246][247][248][249][250], and the NLPR3 inflammasome [243], decrease levels of pro-inflammatory cytokines IL-1␤ [226,229,231,232,236,…”