Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NFκB, AP-1, COX-2, and iNOS in mouse epidermis

Abstract

Resveratrol, a phytoalexin present in grapes, has been reported to inhibit multistage mouse skin carcinogenesis. Recent studies showed that topically applied resveratrol significantly inhibited cyclooxygenase-2 (COX-2) expression and activation of nuclear factor-kappaB (NF-kappaB) induced by tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis. The aim of the present study was to further explore the effect of resveratrol on TPA-induced signaling pathways in mouse epidermis and to compare with its dimethylether, pterostilbene. Resveratrol and pterostilbene significantly reduced activator protein 1 (AP-1) and NF-kappaB activation. In the case of AP-1, the binding of c-Jun subunit was particularly affected, while only slight effect on c-Fos binding to TPA-responsive element (AP-1 binding consensus sequence) (TRE) site was observed. Both stilbenes inhibited the activation of NF-kappaB by blocking the translocation of p65 to the nucleus and increasing the retention of IkappaBa in the cytosol. The latter might be related to decreased activity of IkappaB kinase and/or proteasome 20S. Reduced activation of transcription factors decreased the expression and activity of COX-2 and inducible nitric oxide synthase (iNOS). In most assays, pterostilbene was either equally or significantly more potent than resveratrol. Pterostilbene might show higher biological activity due to its possible better bioavailability, since substitution of hydroxy with methoxy group increases lipophilicity.

Pterostilbene protects against acute renal ischemia reperfusion injury and inhibits oxidative stress, inducible nitric oxide synthase expression and inflammation in rats via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway

“…The results of the present study demonstrated that Pter significantly decreased NF-κB protein expression levels in the renal tissues of rats that had undergone renal IRI. Cichocki et al (27) reported that Pter inhibited 12-O-tetradecanoylphorbol-13-acetate-activated NF-κB and iNOS expression in the mouse epidermis.…”

Determination of pterostilbene in rat plasma by a simple HPLC‐UV method and its application in pre‐clinical pharmacokinetic study

“…In mammalian pharmacology, pterostilbene possesses various disease-fighting effects. Its cancer chemo-preventive effects have also been observed in two rodent models (Cichocki et al, 2008;Suh et al, 2007). As an intervention, pterostilbene significantly induced growth arrest and/or apoptosis in various transformed cells (Billack et al, 2008;Ferrer et al, 2005;Pan et al, 2007;Priego et al, 2008;Remsberg et al, 2008;Rimando and Suh, 2008;Tolomeo et al, 2005).…”

Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo

“…PT inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation of vascular smooth muscle cells (VSMCs) and DNA synthesis [15], so PT might be a potential anti-proliferative agent for treating of atherosclerosis. Furthermore, PT may have anti-oxidant and anti-neoplastic activities as effective as those of resveratrol because of the structural similarity of the two agents [16].…”