Gold nanoparticles phytoreduced with Cornus mas extract mitigate some of gliadin effects on Caco-2 cells.

Celiac disease (CD) is an autoimmune condition that occurs in genetically predisposed people where the ingestion of gluten produces damage in the small intestine. The treatment accepted until now is a strict gluten free diet. This implies the need for novel or adjuvant treatments, in addition to the standard of care. The present study aimed to assess the effect of gold nanoparticles phytosynthesized with Cornus mas extract (AuCM) compared to Cornus mas extract (CM) and luteolin (LT) on Caco-2 cells, exposed or not to gliadin. Ultraviolet-visible spectroscopy and transmission electron microscopy were used for the characterization of AuCM. Measured cellular outcomes included oxidative stress markers (malondialdehyde level, catalase and superoxide dismutase activities), inflammatory response and cellular signaling and transcription factors involved in apoptosis (NFκB, pNFκB, NOS2, TNF-α, TRAIL, Bax, Bcl-2, p53). The internalization of gold nanoparticles in cells was evidenced by transmission electron microscopy (TEM). The gliadin administration induced oxidative stress, improved the activity of antioxidants enzymes, increased NOS2 and NFκB expressions and reduced pNFκB/NFκB ratio. In addition, gliadin enhanced TRAIL and Bcl-2 levels and reduced p53 expression in Caco-2 cells. The pretreatment with AuCM, CM extract and LT diminished oxidative stress and reduced NOS2 activity. AuCM and CM treatment amplified the expression of p53 and pNFκB/NFκB ratio and diminished Bcl-2, NFκB and pNFκB, especially AuCM. The results obtained confirmed that AuCM mitigate some of gliadin effects on Caco-2 cells through modulation of oxidative stress and inflammation.

The effect of Tropaeolum majus L. on bacterial infections and in vitro efficacy on apoptosis and DNA lesions in hyperosmotic stress.

Tropaeolum majus L. (T. majus) or nasturtium is a medicinal plant widespread in the areas with temperate climate, commonly used in culinary and in traditional medicine due to therapeutic properties. In the last few years, various effects of the flowers and leaves of this plant have been studied, but their benefits are not fully known. The aim of the study was to identify the phenolic compounds from T. majus edible flowers in relation with its antioxidant capacity and the antimicrobial activity against different bacteria and Candida albicans. In addition, the impact of natural extract on oxidative stress, inflammation and apoptosis was analysed on human umbilical vein endothelial cells (HUVECs) exposed to normotonic and hypertonic conditions. The major phenolic acids, identified by HPLC-RP with UV detection, were gallic acid, caffeic acid and p-coumaric and predominant flavonoids were quercetin, epicatechin and luteolin. The both fractions of T. majus were rich sources of polyphenols with marked antioxidant activity, evidenced by TEAC or DPPH methods. The extract exhibited a week antibacterial effect on some strains of streptococcus, without antifungal or antibacterial effect on gram negative bacteria. T. majus extract increased the p53 and Bcl-2 expressions and diminished the DNA lesions indicating the protective and antiapoptotic effects in vitro, on endothelial cells exposed to hyperosmotic stress. These experimental findings suggest that T. majus can exert some protection against bacterial infections and reduce apoptosis and DNA lesions in hypertonic conditions.

Characterization and biological effects of Hypericum extracts on experimentally-induced - anxiety, oxidative stress and inflammation in rats.

Anxiety disorders can associate with oxidative stress and immune system alterations. Our study aimed to chemically analyze Hypericum maculatum (HM) and Hypericum perforatum (HP) dry extracts and to evaluate their effects along with quercetin (Q), on brain oxidative stress biomarkers: malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD), inflammatory cytokines: interleukin-1α, (IL-1α), IL-1ß, regulated on activation normal T cell expressed and secreted (RANTES), interferon (IFN), monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein (MIP) and serum corticosterone levels. Nuclear transcription factor κB (NFκB) signaling pathway in the hippocampus and frontal lobe in rats with N-methyl-9H-pyrido[5,4-b]indole-3-carboxamide (FG-7142) experimental-induced anxiety were also investigated. The chemical analyses of total hypericins were performed by spectrophotometric analysis and hypericin, hyperforin and polyphenols derivatives were quantified by chromatographic methods. The animals were divided in 6 groups: carboxymethylcellulose 2% (CMC); CMC + FG; alprazolam (APZ) + FG; Q + FG; HM + FG; HP + FG. APZ (0.08 mg/kg b.w.), Q (30 mg/kg b.w.), HM and HP (350 mg/kg b.w.) were orally administered for 21 days. FG (7.5 mg/kg b.w.) was intraperitoneally (i.p.) injected in a single dose. Q and hypericum extracts (HpE) exerted anti-inflammatory (decreased IL-1α, IL-1ß, MCP1, IFN and MIP mainly in hippocampus) and antioxidant effects (decreased MDA levels, increased CAT and SOD activity), enhanced NFκB and pNFκB expressions in the brain and reduced serum corticosterone levels. Our findings suggest that HpE may improve anxiety-like behavior, offer brain protection by modulation of oxidative stress and inflammation, and can contribute to overall biological activity of natural compounds-rich diet.

In vitro studies on the mechanisms involved in chemoprevention using Calluna vulgaris on vascular endothelial cells exposed to UVB.

The study aims to investigate the mechanisms involved in the in vitro effect of UVB on endothelial vascular cells (HUVECs) pretreated with a photochemopreventive agent, the Calluna vulgaris (Cv) extract. Two concentrations of Cv, below the limit of cytotoxicity IC50 (2.5 and 7.5 µg GAE/ml) and two doses of UVB (50 and 100 mJ/cm(2)) were used. Oxidative stress parameters were quantified at 1 h and 24 h after irradiation and apoptosis, DNA damage and the induction/activation of NF-κB were evaluated at 24 h. UVB exposure led to the formation of lipid peroxides in a dose dependent manner (p<0.001), induced apoptosis, increased the γ-H2AX levels and the activation of NF-κB. Pretreatment with 2.5 µg GAE/ml Cv improved the antioxidant defense, protected against DNA lesions and was able to decrease cellular death at low dose of irradiation. 7.5 µg GAE/ml Cv was prooxidant, favored the formation of DNA lesions, amplified the NF-κB activation UVB-induced (p<0.01) and led to high levels of cellular death. Both doses of Cv inhibited caspase-3 activation. The modulatory effect of Cv extract on endothelial cells exposed to UVB depend on the concentration of Cv used. This study provides insides into the mechanisms triggered by UVB and antioxidants on skin endothelial cells.

Calluna vulgaris extract modulates NF-κB/ERK signaling pathway and matrix metalloproteinase expression in SKH-1 hairless mice skin exposed to ultraviolet B irradiation.

Photochemoprevention with natural products represents a new concept in the attempt to reduce the occurrence of skin cancer. However, the molecular mechanisms caused by ultraviolet light exposure remain still unclear. The aim of the study was to assess the mechanisms involved in the action of a Calluna vulgaris (Cv) extract, administered in single or multiple doses (10 consecutive days), on UVB-induced skin damage in SKH-1 hairless mice. The extract was topically applied 30 min before each UVB exposure in two doses (2.5 and 4 mg total polyphenolic content/40 µl/cm(2)). At 24 hours after the last treatment, total mitogen-activated protein kinase (p44/42MAPkinase, ERK 1/2), nuclear factor-κB (phospho-NF-κB p65), matrix metalloproteinases (MMP-2, MMP-9) and metalloproteinase inhibitor 1 (TIMP-1) levels were measured in skin using enzyme-linked immunosorbent assay (ELISA). MMP-2 and -9 activities were additionally evaluated by zymography. One topical application of Cv extract reduced the secretion (p<0.004) and inhibited MMP-9 activity UVB-mediated (54% inhibition) via inhibition of NF-κB activation (68% inhibition). In multiple UVB exposures, both doses of Cv extract induced the increase of ERK 1/2 level in correlation with activation of NF-κB and reduced the secretion (p<0.04) and activation of MMP-9 (62% inhibition). Pretreatment with Cv diminished the MMP-2 protein secretion only in one dose UVB-irradiated group (p<0.0001) and decreased TIMP-1 level (p<0.001). These results demonstrated the dual behavior of Cv extract in skin protection against single versus multiple doses of UVB irradiation.

Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB-induced skin damage in SKH-1 hairless mice.

Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 µl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.

Studies on antioxidant effects of the red grapes seed extract from Vitis vinifera, Burgund Mare, Recas in pregnant rats.

To estimate the effects of hydroethanolic red grapes seeds extract obtained from Vitis vinifera, Burgund Mare variety, Recas , Romania (BMR) on oxidant-antioxidant ballance, as compared to ascorbic acid, during pregnancy in rats. Thirty Wistar female rats were assigned to three groups (n=10) which were administered by gavage: Group I, 3 x 100 mg/kg body weight saline, Group II - BMR 3 x 30 mg gallic acid equivalents/kg body weight; Group III - vitamin C 3 x 100 mg/kg body weight on days 1, 7 and 14 of pregnancy. On day 21 blood samples were collected. Malon dyaldehyde, lipid peroxides, protein carbonyls, nitric oxide (as oxidative stress parameters) and hydrogen donor ability and total thiol groups (as antioxidant parameters) serum concentrations were measured. Vitamin C significantly enhanced the antioxidant capacity of plasma (hydrogen donor ability, p=0.0001; thiol groups, p=0.0001), as well as nitric oxide levels (p=0.001). The extract increased the plasma antioxidant capacity (hydrogen donor ability, p=0.001; thiol groups p=0.001) and did not elevate the nitric oxide plasma levels in pregnant rats.In conclusion, in the chosen dose, the red grapes seed extract enhanced the plasma antioxidant capacity and did not influence the nitric oxide levels in pregnant rats.

Photochemoprevention of cutaneous neoplasia through natural products.

Non-melanoma skin cancers such as squamous cell carcinoma and basal cell carcinoma are the most common types of human tumors, representing 30% of the new cases of malignancies diagnosed each year. Ultraviolet radiation (UV) from the sun is a major cause of non-melanoma skin cancer in humans. The prevention and mainly the photochemoprevention with natural products represent a simple but very effective strategy in the management of cutaneous neoplasia. Here we review the progress in the research of new and existing agents developed to protect the skin exposed to UV. We also discuss the current state of knowledge on their photosuppression mechanism in humans as well as in animal models, and efficiency in cancer prevention.

Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones.

Environmental iodine deficiency continues to be a significant public health problem worldwide. On the other hand, iodide excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. For this reason we intended to explore iodide excess impairment on prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood and the effect of selenium administration on oxidative stress markers under the same circumstances. Experiments were performed for 10 days with white, male, Wistar rats, as follows: group 1: control-normal iodine supply group; 2: high iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet and Carbimasole. Oxidative stress markers such as lipid peroxides were determined in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the sera and catalase activity in thyroid gland and in hepatic tissue assessed antioxidant defense. Iodide excess had prooxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and in blood and to a decreased H+ donor ability of the sera. Selenium supplementation had opposite effects. Present data allow us to conclude that the alterations due to iodide excess in thyroid gland, hepatic tissue and in blood are mediated through oxidative stress.