Dietary grape seed proanthocyanidins inhibit UVB-induced oxidative stress and activation of mitogen-activated protein kinases and nuclear factor-κB signaling in in vivo SKH-1 hairless mice

Abstract

We have shown previously that dietary grape seed proanthocyanidins (GSP) inhibit UVB-induced photocarcinogenesis in mice. As UVB-induced oxidative stress and oxidative stress -mediated signaling has been implicated in photocarcinogenesis, this study was designed to investigate the effect of dietary GSPs on UVB-induced oxidative stress in in vivo SKH-1 hairless mice. Here, we report that provision of dietary GSPs (0.2 and 0.5%, w/w) to mice exposed to either acute UVB irradiation (120 mJ/ cm 2 ) or chronic irradiation of UVB inhibited depletion of glutathione peroxidase, catalase, and glutathione, and inhibited UVB-induced H 2 O 2 , lipid peroxidation, protein oxidation, and nitric oxide in mouse skin. As UV-induced oxidative stress mediates activation of mitogen-activated protein kinase (MAPK) and nuclear factor-KB (NF-KB) signaling pathways, we determined the effect of dietary GSPs on these pathways. We observed that dietary GSPs inhibited UVB-induced phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun-NH 2 -kinase, and p38 proteins of MAPK family, which seems to be mediated through reactivation of MAPK phosphatases. GSPs inhibited UVB-induced activation of NF-KB/p65 through inhibition of degradation of IKBA and activation of IKB kinase A (IKKA). As NF-KB -targeted genes play critical roles in inflammation and cellular proliferation, we assessed the effect of GSPs on proteins encoded by these genes. Dietary GSPs resulted in inhibition of the expression of proliferating cell nuclear antigen, cyclin D1, inducible nitric oxide synthase, and cyclooxygenase-2 in the skin. Collectively, our data show that GSPs have the ability to protect the skin from the adverse effects of UVB radiation via modulation of the MAPK and NF-KB signaling pathways and provide a molecular basis for the photoprotective effects of GSPs in an in vivo animal model.

Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non–Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors

“…The GSPs preparation contains ∼89% proanthocyanidins, with dimers (6.6%), trimers (5.0%), tetramers (2.9%), and oligomers (74.8%) as described earlier (26,27). GSPs are stable for at least 2 y when refrigerated at 4°C.…”

“…Grape seed proanthocyanidins (GSP) have anticarcinogenic properties (25) and seem to exhibit minimal toxicity (26,27). GSPs are a mixture of polyphenols/flavanols and primarily contain proanthocyanidins (89%), which constitute dimers, trimers, tetramers, and oligomers/polymers of monomeric catechins and/or (−)-epicatechins (25,27).…”

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

“…Recent studies have used systemic and topical antioxidants in murine model systems to modulate UV effects [95][96][97][98] . The relative favorable safety profile of antioxidants has allowed human studies (reviewed in [99][100][101] ).…”

Presence of tannins in sorghum grains is conditioned by different natural alleles of Tannin1

“…Tannins, also known as condensed tannins or proanthocyanidins (PAs), are oligomers and polymers of flavan-3-ols. Beneficial effects from diets rich in tannin-containing foodstuffs include immunomodulatory and anticancer activity; antioxidant and radical scavenging functions; antiinflammatory, cardioprotective, vasodilating, and antithrombotic effects; and UV-protective functions (1,4). Tannins are widespread throughout the plant kingdom, with diverse biological and biochemical functions, such as protection against predation from herbivorous animals and pathogenic attack from bacteria and fungi (5).…”