Vinpocetine Suppresses Inflammatory and Oxidative Machineries in Acute Model of Inflammation—Pivotal Role of COX-2 Signaling

Abstract

The presence of inflammation is one of the key factors in the onset and progression of various medical disorders and diseases, making it a crucial challenge for treatment. The purpose of this study is to evaluate antioxidant and anti-inflammatory effects of Vinpocetine, using acute models of inflammation; Xylene-, Carrageenan (CGN)-induced inflammation and acetic acid-induced vascularpermeability in mice were used. We also employed molecular docking approach to verify the underlying mechanism of anti-inflammatory activity of Vinpocetine. In a current investigation, Vinpocetine showed anti-inflammatory and antioxidant effects on Xylene-and CGN-induced inflammation in a dose-dependent manner. Vinpocetine reduced inflammatory edema and restored antioxidant tissue balance, probably via suppression of IL-1β, IL-6, TNF-α, MDA and MPO activity, and also through increased non-enzymatic antioxidant (GSH) levels in paw tissue. Histopathological examination showed that Vinpocetine restored normal skin architecture with significant inhibition of tissue edema, congestion, and cellular infiltration in CGN-challenged paw. Mechanistically, Vinpocetine showed downregulation the expression of COX-2 protein, in western blot assessment, that was associated with significant decrease in the level of prostaglandin E 2 (PGE2) levels; a major metabolic product of COX-2 enzyme. Interestingly, Silico study showed that Vinpocetine has strong affinity to COX-2, similar to diclofenac, suggested possible mechanism of downregulation of COX-2 expression. Therefore, Vinpocetine showed antioxidant and anti-inflammatory responses might, in part, due to inhibition of COX-2/PGE 2 pathway.

Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

“… 109 Another study has reported that VNP restores natural skin morphology in carrageenan-induced paw skin, possibly by inhibiting tissue oedema, congestion, immune cell invasion, NF-κB expression, and the generation of detrimental inflammatory molecules comprising TNF-α, myeloperoxidase, COX-2, and prostaglandin (PGE)-2. 110 This agent also relieves pain associated with inflammatory conditions by eliminating NF-κB activation, paw skin cytokine generation, and cellular oxidative damage. 111 Additionally, the medication accelerates wound healing in diabetic rat skin and regenerates the skin's structural features, by decreasing epidermal thickness, renewing dermal granulation, and increasing collagen fibre formation.…”