Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice

Abstract Purpose To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). Methods Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. Results Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. Conclusion GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.

Hepatic protective effect of grape seed proanthocyanidin extract against Gleevec-induced apoptosis, liver Injury and Ki67 alterations in rats

ABSTRACT Gleevec (imatinib) is an antineoplastic chemotherapeutic agent used in the treatment of many types of cancer. The current study was conducted to examine the possible modifying effects of grape seeds proanthocyandins extract (GSPE) against apoptosis, liver injury and Ki67 alterations induced by Gleevec in male rats. 40 male albino rats were equally divided into four groups (First and second groups were control and GSPE groups; third group was Gleevec group and fourth group was treated with Gleevec and GSPE). Gleevec induced elevations in P53 and depletion of Bcl2 levels in liver tissues were compared with the control group. Liver sections in rats treated with Gleevec exhibited marked cellular infiltrations, vacuolar degeneration hepatocytes, numerous apoptotic cells, and congestion in central and portal veins, as well as a significant increase in the proliferating of Ki67 after Gleevec injection as compared with control group. In contrast, treatment with Gleevec and GSPE showed a moderate to good degree of improvement in hepatocytes with a significant increase in Ki67, a decrease in P53 and an increase in Bcl2 levels in liver tissues compared to treatment with Gleevec. Therefore, Gleevec induces apoptosis, injury and Ki67 changes in rat liver, whereas GSPE modulates these alternations.

Effects of grape seed extract on periodontal disease: an experimental study in rats

Abstract Natural compounds capable of modulating the host response have received considerable attention, and herbal products are suggested as adjunctive agents in periodontal disease treatment. Objective This study aimed to demonstrate the effect of grape seed extract (GSE) on periodontitis. Material and Methods Ligature induced periodontitis was created in 40 rats and they were assigned to four equal groups. One group was fed laboratory diet (group A) while three groups received GSE additionally. Silk ligatures were placed around the cervical area of the mandibular first molars for four weeks to induce periodontitis. The GSE groups were reallocated regarding GSE consumption as: for two weeks before ligation (group B; totally eight weeks), from ligation to two weeks after removal of the ligature (group C; totally six weeks), and for two weeks from ligature removal (group D; totally two weeks). Sections were assessed histologically and immunohistochemically. Inflammatory cell number (ICN), connective tissue attachment level (CAL), osteoclast density (OD), IL-10 and TGF-β stainings in gingival epithelium (GE), connective tissue (GC), and periodontal ligament (PL) were used as the study parameters. Results Lower ICN, higher CAL, and lower OD were observed in the GSE groups (p<0.05). IL-10 was more intensive in the GSE groups and in the GEs (p<0.05). Group B showed the highest IL-10 for PL (p<0.05). TGF-ß was higher in the GEs of all groups (p<0.017). Conclusions The results suggest anti-inflammatory activities of GSE, but further investigations are needed for clarification of these activities.

Atividade antimicrobiana do extrato de semente de uva Vitis vinifera sobre biofilme de Enterococcus faecalis: análise com microscopia confocal / Antimicrobial effectiveness of grape seed extract against Enterococcus faecalis biofilm: confocal microscopy analysis

As limitações dos irrigantes químicos utilizados em endodontia têm incentivado novas pesquisas acerca de substâncias alternativas para serem utilizadas no tratamento endodôntico. Estudos anteriores sugerem que o extrato de semente de uva (Vitis vinifera), tem atividade antimicrobiana assim como é eficaz no combate a cepas de Enterococcus faecalis. No entanto, os efeitos deste novo irrigante em biofilmes microbianos ainda não foram elucidados. Dessa forma, o objetivo deste estudo foi avaliar e quantificar o grau de desinfecção da dentina contaminada por biofilme de E. faecalis após irrigação com extrato de semente de uva Vitis vinífera 6,5% por meio de análise microscopia confocal a laser. A clorexidina (CHX) 2% e o hipoclorito de sódio (NaOCl) 5,25% foram utilizados como irrigantes para comparação. Foram confeccionadas quarenta amostras de discos de dentina que foram contaminadas com E. faecalis e incubadas por um período de 21 dias para formação do biofilme. As amostras foram divididas em diferentes grupos de acordo com o irrigante testado após transcorrido o período de contaminação: grupo NaOCl, grupo CHX, grupo Vitis vinifera e grupo solução salina (controle). Após a irrigação, os discos de dentina foram corados com o corante fluorescente LIVE/DEAD BacLight e analisados por microscopia confocal à laser para determinar a proporção de células mortas no biofilme. A aquisição das imagens e quantificação do biofilme foi realizada utilizando-se o software LAS X. Uma distribuição normal dos dados foi confirmada pelo teste Shapiro- Wilk (p>0,05). Por esse motivo, a análise estatística foi realizada utilizando-se One-way análise de variância. Comparações Post hoc pair-wise foram realizadas utilizando-se o teste Tukey para múltiplas comparações (P<0.05). O grupo no qual o NaOCl foi utilizado como irrigante apresentou maior quantidade de células bacterianas mortas do que os dos outros irrigantes (P<0,05). Já o grupo da Vitis vinifera demonstrou maior morte bacteriana quando comparada a CHX e ao grupo controle (P<0,05). Não foram observadas diferenças entre a CHX e o grupo controle (P>0,05). A irrigação com o extrato de semente de uva, vitis vinífera, apresentou atividade antimicrobiana sobre o biofilme de E. faecalis sendo esta inferior a apresenta pelo NaOCl e superior a apresentada pela CHX.

The limitations of chemical irrigants used in endodontics have encouraged further research on alternative substances to be used in endodontic treatment. Previous studies have suggested that grape seed extract (Vitis vinifera), an irrigant of natural origin, is effective against strains of Enterococcus faecalis. The aim of this study was to evaluate and quantify the degree of disinfection of dentin contaminated by E. faecalis biofilm after irrigation with Vitis vinifera grape seed extract 6,5% and to compare it with chlorhexidine (CHX) 2% and Sodium hypochlorite (NaOCl) 5,25% by confocal microscopy laser. Forty samples of dentin disks that will be contaminated with E. faecalis and incubated for a period of 21 days for biofilm formation were prepared. The samples were divided into different groups according to the irrigant tested after the period of contamination: NaOCl group, CHX group, Vitis vinifera group and control group . After irrigation, the dentin disks were stained with the fluorescent dye LIVE / DEAD BacLight and analyzed by laser confocal microscopy to determine the proportion of dead cells in the biofilm. The acquisition of the images and quantification of the biofilm was performed using the software LAS X. Normal distribution of the data was confirmed by Shapiro- Wilk test (p>0.05). Therefore, statistical analysis was performed using One-way analysis of variance. Post hoc pair-wise comparisons were performed using Tukey's test for multiple comparisons (P<0.05). NaOCl presented a higher amount of bacterial cells killed than the other irrigators (P <0.05). Irrigation with grape seed extract, Vitis vinifera, showed antimicrobial activity on the E. faecalis biofilm, being lower than that presented by NaOCl and higher than that presented by CHX.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

Clinical, biometric and ultrasound assessment of the effects of daily use of a nutraceutical composed of lycopene, acerola extract, grape seed extract and Biomarine Complex in photoaged human skin / Avaliações clínica, biométrica e ultrassonográfica dos efeitos do uso diário de um nutracêutico a base de licopeno, extrato de acerola, extrato de semente de uva e Complexo Biomarinho na pele fotoenvelhecida humana

BACKGROUND: The use of nutraceuticals has become frequent in the cutaneous approach to photoaging. OBJECTIVES: To assess the clinical efficacy of a nutraceutical product composed of lycopene, acerola extract, grape seed extract and Biomarine ComplexT in photoaged human skin. METHODS: 50 women, from 35 to 60 years of age, phototypes I to III, were assessed. For 120 days, they associated the nutraceutical product with the use of a sunscreen FPS15. On days 0 (D0), 30 (D30), 60 (D60), 90 (D90) and 120 (D120) they were evaluated and underwent Medical Assessments and Self-Assessment and cutaneous biometric analyses (corneometry, sebumetry and pH-metry) in the skin of the left zygomatic region and the upper medial side region of the left arm; on days 0 (D0), 30 (D30) and 120 (D120) the skin of the same regions was analyzed by ultrasound. On days 0 (D0) and 120 (D120) skin biopsies were performed in the areas where instrumental evaluation was performed (to evaluate collagen and elastic fibers). RESULTS: There was an improvement of the general status of the skin of all volunteers by the Medical and Volunteer Self- Assessments; increased parameters of cutaneous hydration, reduction of pH, increasing of ultrasound density and a histological increment of collagen and elastic fibers (both on the face and arm); there was a reduction of seborrhea (only on the face) CONCLUSIONS: The daily use of a nutraceutical product containing lycopene, acerola extract, grape seed extract and Biomarine ComplexT showed an important adjuvant effect to counteract skin photoaging.

FUNDAMENTOS: O uso de nutracêuticos se tornou uma condição frequente na abordagem cutânea do fotoenvelhecimento. OBJETIVOS: Avaliar a eficácia clínica do uso de um produto nutracêutico a base de licopeno, extrato de acerola, extrato de semente de uva e Complexo BiomarinhoT na pele fotoenvelhecida humana. MÉTODOS: Foram avaliadas 50 mulheres, de 35 a 60 anos de idade, fototipo I a III. Por 120 dias, elas associaram ao uso de fotoprotetor FPS15 a tomada diária do produto nutracêutico em questão. Nos dias 0 (D0), 30 (D30), 60 (D60), 90 (D90) e 120 (D120) elas foram avaliadas, quando sofreram Avaliações Médica e Auto-Avaliação e análises biométricas cutâneas (corneometria, sebumetria e pHmetria) nas peles da região zigomática esquerda e face súpero-medial do braço esquerdos; nos dias 0 (D0), 30 (D30) e 120 (D120) a pele das mesmas regiões foram analisadas do ponto de vista ultrassonográfico. Nos dias 0 (D0) e 120 (D120) biópsias cutâneas foram realizadas nas respectivas áreas das análises instrumentais (para avaliar colágeno e das fibras elásticas). RESULTADOS: Houve melhora do estado geral da pele de todas as voluntárias pelas Avaliações Médica e Voluntária; aumento alterações dos parâmetros cutâneos na hidratação, redução do pH cutâneo, aumento da densidade ultrassonográfica e aumento histológico na densidade colágena e elástica (tanto na face quanto no braço); redução da seborreia somente na face. CONCLUSÕES: O uso diário de um produto nutracêutico a base de licopeno, extrato de acerola, extrato de semente de uva e Complexo BiomarinhoT mostra-se um adjuvante importante na abordagem do fotoenvelhecimento cutâneo.