Orbital decompression surgery and horse chestnut seed extract improved superior orbital vein blood flow in patients with thyroid-associated ophthalmopathy

AIM： To evaluate the efficacy and safety of orbital decomposition （OD） surgery in combination with horse chestnut seed extract （HCSE）, as compared to OD atone, in patients with thyroid-associated ophthalmopathy （TAO）. METHODS： Sixty-two orbits from 62 TAO patients were randomly assigned to OD or OD＋HCSE at 1：1 ratio （31 received OD alone, 31 received OD ＋HCSE）. Forty-two orbits from 21 healthy subjects were used as controls. Complete ophthalmic examination and color Doppler flow imaging （CDFI） were performed before surgery and 3mo post-surgery on all 62 orbits from the TAO patients. CDFI were also performed on the 42 control orbits, The effect of OD ＋HCSE and OD alone on TAO orbits was compared on several endpoints, including superior ophthalmic vein blood flow （SOVBF） parameters, subjective assessment, soft tissue involvement, lid retraction, diplopia, eye movement restriction, degree of exophthalmos, and intraocular pressure. The control orbits were used as reference for the SOVBF parameters. RESULTS： OD surgery with or without HCSE improved SOVBF, symptoms and soft tissue involvement, decreased degree of exophthalmos and intraocular pressure in orbits of TAO patients. The OD ＋HCSE combination led to significantly better improvement of SOVBF than OD alone. The differences between the reductions of SOVBF in the two groups are 1.26 cmls in max-volecity and 0.52 cm/s in min-voiecity （P〈0.0001）. CONCLUSION： SOVBF is significantly reduced in the orbits affected with TAO, indicating that congestion may be an important factor contributing to TAO pathogenesis. OD surgery improves the SOVBF, and combination of HCSE medication and OD surgery further improved venous return than OD surgery alone.

Effects of grape seed extract on meat color and premature browning of meat patties in high-oxygen packaging

This study investigated the effects of grape seed extract(GSE)on fresh and cooked meat color and premature browning(PMB)in ground meat patties(85% beef and 15% pork back fat)packaged under high-oxygen modified atmospheres(HiOx-MAP).The GSE was added to patties at concentrations of 0,0.10,0.25,0.50 and 0.75 g kg^(-1).This study evaluated the surface color,pH,lipid oxidation,and total viable counts(TVC)of raw patties,and the internal color and pH of patties cooked to a temperature of 66 or 71℃ over 10-day storage at 4℃.Compared with the control(0 g kg^(-1) GSE),GSE improved the color stability(P<0.05)and significantly inhibited the lipid and myoglobin oxidation of raw patties from day 5 to 10,but GSE had no effect(P>0.05)on TVC.Patties containing 0.50 and 0.75 g kg^(-1) GSE cooked to 66℃ exhibited greater(P<0.05)interior redness than the control and reduced the PMB of cooked patties in the late storage stage.These results suggested that 0.50 and 0.75 g kg^(-1) GSE can improve fresh meat color and minimize PMB of HiOx-MAP patties.

Add-on therapy of herbal formulation rich in standardized fenugreek seed extract in type 2 diabetes mellitus patients with insulin therapy: An efficacy and safety study

Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.

Vitamin C, Grape Seed Extract and Citrus Bioflavonoids Protect the Skin against Photoaging: A Review

The skin is a major protective organ of the body. It is constantly exposed to the environment and is very resilient. But exposure to ultraviolet (UV) rays from the sun results in the production of reactive oxygen species (ROS) and subsequent inflammatory responses that can overwhelm the innate protective mechanisms of the skin. This results in damage and premature aging. Strategies to mitigate this premature photoaging might include avoidance of sunlight. However, some sunlight exposure is beneficial to health. One notable example of this is the production of vitamin D. A more practical approach to preventing adverse effects of UV light in the skin is antioxidant supplementation. Dietary antioxidants may help control ROS propagation following UV light exposure. To further evaluate the utility of antioxidants in protecting the skin, in vitro, in vivo and human studies of three well known dietary antioxidants are reviewed and discussed. The data clearly demonstrate that vitamin C, grape seed extract and citrus bioflavonoids have the potential to reduce the damaging effects of excess sun exposure via antioxidant, anti-inflammatory and immunomodulating mechanisms. As such, regular ingestion of dietary antioxidants appears to be a useful strategy for protecting the skin against photoaging.

Grape Seed Extract and the Fetal Ductus Arteriosus: A Potential Danger of a Common Herbal Supplement

A female at 28 weeks gestation was referred to pediatric cardiology for a fetal arrhythmia. The echocardiogram revealed premature constriction of the fetal ductus arteriosus. Her work up was unremarkable except for her use of an herbal supplement, grape seed extract, which is advertised as a potent anti-inflammatory medication, and has biochemical properties similar to other medications that have been shown to cause premature ductal constriction. The use of herbal remedies increases each year. Although the public is inundated with radio, television, and internet advertisements for these products, little unbiased information regarding the possible dangers of toxicity or adverse reactions exists. As physicians, we need to be aware of these products, and counsel our patients accordingly.

In vitro antimicrobial effects of grape seed extract on peri-implantitis microflora in craniofacial implants

Objective:To determine the antimicrobial effects of grape seed on peri-implantitis microflora.Methods:The grape seed extract was tested against peri-implantitis microflora most commonly found in craniofacial implants including reference strains of Staphylococcus aureus(S.aureus),Escherichia coli(E.coli),Candida albicans(C.albicans)and clinical strains of S.aureus,Klebsiella pneumonia(K.pneumonia)and Candida parapsilosis(C.parapsilosis)by disk diffusion test.Minimum inhibitory concentrations(MIC)and minimum cidal concentrations(MCC)were determined using modified agar dilution millpore method.The extract was further combined with polyethylene glycol and propylene glycol,and was tested for antimicrobial effects.Results:Grape seed extract showed positive inhibitory effects with S.aureus at MIC of 0.625 mg/mL and MCC of1.25 mg/mL respectively.However the extracts showed minimal or no reactivity against strains of E.coli,K.pneumonia,C.parapsilosis and C.albicans.The use of grape seed extract in combination with polyethylene glycol and propylene glycol also showed dose dependent inhibitory effect on S.aureus.Conclusions:The results of the study showed that grape seed has potential antimicrobial effects which can be further studied and developed to be used in the treatment of infected skinabutment interface of craniofacial implants.

Efficacy of seed extracts of Annona squamosa and Annona muricata(Annonaceae) for the control of Aedes albopictus and Culex quinquefasciatus(Culicidae)

Objective:To evaluate the potential efficacy of seed extracts of Annona squamosa and Annona muricata used as natural insecticides to control adult and larvae of the vectors Aedes albopictus and Culex quinquefasciatus under laboratory conditions.Methods:Aqueous and oil extracts of the two plants were prepared from dried seeds.Preliminary identifications of the chemical components of each seed extracts were performed using microreactional and GCP techniques.Larvae and adults of Aedes albopictus and Culex quinquefasciatus were collected from the breeding sites in coastal and highlands regions of Madagascar.WHO standardized tests of susceptibility for larvae and imaginal stage of mosquitoes were realized to determine mortality and LC_(50) of mosquitoes.Results:Chemical identifications showed that these extracts contain alkaloids and flavonoids compounds that probably confer their biological insecticidal proprieties.CPG analysis showed also the presence of various fatty acids.On adult mosquitoes,significant insecticidal effects were observed with both aqueous and oil extracts of the two plant seeds compared to mortality induced by deltamethrin,an insecticide used as reference.Extracts of Annona muricata induced high mortality rate to both species of mosquito compared to extracts of Annona squamosa at all concentrations tested.The LC_(50) of seed extracts ranged from 1%to 5%for adults and 0.5%to 1%for larvae.Conclusions:The seed extracts of these two plants may be used as mosquito controlling agents and offer a new approach to a less costly,practical and environmentally friendly control of vector borne diseases.

Trigonella foenum-graecum seed extract modulates expression of lipid metabolism-related genes in HepG2 cells

Objective:To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts,diosgenin,and 4-OH-Ile on HepG2 cell line.Methods:HepG2 cells were treated with hydroalcoholic fenugreek seed extracts,diosgenin,4-OH-Ile,and orlistat.IC20 was calculated using the MTT method.The cells were then pretreated with IC20 concentrations for 24 and 48 h.Real time PCR was employed to measure expression of liver X receptor alpha(LXR a),sterol regulatory element-binding protein-1 C(SREBP-1 C),acetyl-CoA carboxylase(ACC),fatty acid synthase(FAS),fibroblast growth factor 21(FGF21),peroxisome proliferator-activated receptor gamma(PPAR γ),and lowdensity lipoprotein receptor(LDLR).Results:The results showed that LXR α(P=0.003,P<0.001).,SREBP-1 C(P<0.001,P<0.001),ACC(P=0.002,P=0.006),and FAS(P<0.001,P<0.001)were downregulated significantly,while FGF21(P<0.001,P<0.001),PPAR γ(P=0.004,P<0.001),and LDLR(P<0.001,P<0.001)were upregulated significantly in HepG2 cells treated with the IC20 of hydroalcoholic fenugreek seed extracts,diosgenin,4-OH-Ile,and orlistat in 24 and 48 h,respectively.Conclusions:Hydroalcoholic fenugreek seed extracts,diosgenin,and 4-OH-Ile significantly modulate the expression of some important lipid metabolism related genes,which is similar to orlistat.Trigonella foenum.-graecum seed extract or its derivatives should be further investigated for their dyslipidemia effects and its complications.

Grape Seed Extract (<i>Vitisvinifera</i>) Alleviate Neurotoxicity and Hepatotoxicity Induced by Lead Acetate in Male Albino Rats

Grape seed extracts (GSE) are very potent antioxidant and exhibit numerous interesting pharmacologic activities, including an antioxidant property, and has been suggested to be of use in treatment of several diseases. The present study has been undertaken to investigate the protective and therapeutic effect of GSE against lead-induced neuro and hepatotoxicity in rat. Male albino rats were divided into six groups: the 1st group, rats were injected daily with saline vehicle and served as negative control, the 2nd group (positive control group), the rats were injected (i.p.) with subacute dose (100 mg/kg b·w/day) of lead acetate (LA). The 3rd group (protective group), the rats were injected (i.p.) with LA (100 mg/kg b·w/day) for 7 days after treatment with GSE (100 mg/kg b·w/day) for 3 weeks. The 4th, 5th and 6th groups (therapeutics groups), rats were injected (i.p.) with subacut dose (100 mg/kg b·w/day) of lead acetate for 7 days, then treated with GSE (100 mg/kg b·w/day) for one, two and three weeks, respectively. The level of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA) were evaluated in brain regions (cerebellum, brainstem, striatum, cerebral cortex, hypothalamus and hippocampus). The result indicated that the administration of subacute dose of LA (100 mg/kg/day, i.p.) induce a significant decrease in NE, DA, 5-HT and 5-HIAA content in all tested brain regions. Also the obtained data showed significant increase in liver enzymes: serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT) and Lactate dehydrogenase (LDH) level in group 2 (positive control). There is an improvement in neurotransmitters content. Also the obtained data showed significant in- crease in liver enzymes of protective (G3) and therapeutics groups (G4, G5 and G6) which received GSE compared with animal group that received lead acetate (G2). This is may be the presence of proanthocyanidins and procyanidins which have antioxidant and free radical scavenging activities. The result suggests that grape seed extract may prevent lead-induced neurotoxicity and hepatotoxicity.

The Protective Effect of Grape Seed Extract on Cardiotoxicity Induced by Doxorubicin Drug in Male Rats

Objective: This work was designed to determine the productive effect of grape seed proanthocynadine extract (GSPE) and Vitamin E against Doxorubicin (DOX) induced myocardial toxicity in 50 male. Wister rates were divided in five groups. The 1st group was untreated and served as a control. The 2nd group was treated with DOX only, the 3rd group was pretreated with GSPE, the 4th group was pretreated with Vitamin E, and the 5th group was pretreated with GSPE and Vitamin E. DOX was administered by single i.p (Intraperitonial) injection of 15 mg/kg/body weight to induce cardio toxicity and Vitamin E was administered at a dose of 400 IU/kg/bodyweight/day, p.o (per oral) for 10 days prior to DOX administration [1]. GSPE was given at a dose of 150 mg/kg/bodyweight/ day, p.o (per oral) for 10 days before treatment with DOX. After 2 weeks experimental period, blood samples and heart tissues were taken from all groups. The general observations, mortality, histopathology, biomarker enzymes like Lactate Dehydrogenase (LDH), Creatine Phosphokinase (CPK), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Antioxidants such as Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA) were monitored after 2 weeks of the last dose. Results: Administration of DOX caused cardiomyopathy associated with an antioxidant deficiency. Pretreatment with GSPE and Vitamin E significantly (P < 0.01) protected the myocardium from the toxic effects of DOX by reducing the elevated level of biomarkers and diagnostic enzymes like LDH, CPK, AST, and ALT to normal levels. GSPE and Vitamin E increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Conclusion: These results suggest a cardioprotective effect of GSPE and Vitamin E due to its antioxidant properties.

Effect of False Ragweed (Iva Xanthifolia Nutt) Seed Extracts on Plants

Bioassay method was used to study the biological activity of different polar solvent extracts of False ragweed seed. Specially, water extracts of False ragweed has an effect on plant germination and root length. The study found that False ragweed seed extracts had different degrees of inhibition on many plant seed germinations, and inhibited the germination of cucumber seeds best, the maximum inhibition rate was 79.5%, for cabbage, sorghum and maize seed germination inhibition rate was more than 30%. False ragweed seed extracts also had strong inhibition on cucumber and many other plant root length, and inhibited the root length of cucumber best followed by red beans. The result showed that False ragweed seed extracts contained some materials that could inhibit germination and growth of some plants.

Liver cytochrome P450 system as affected by endophyte-infected tall fescue seed extracts and ergot alkaloids

Endophyte infected tall fescue (E+) is the base diet for nearly all beef cattle in the southern USA. It has been linked to a variety of toxicological conditions due to the presence of large numbers of ergot alkaloids. This study was designed to investigate the effects of E+ seed extract and selected ergot alkaloids on the detoxification pathway by cytochrome P450 (CYP3A4) enzyme system. Tests were performed using the P450- Glo CYP3A4 enzyme activity kit (Promega, WI), according to the manufacturer’s manual. Luminescence was measured using a single tube TD20/20 luminometer. Endophyte infected tall fescue seed was extracted with 50/50 methanol/25 mM ammonium carbonate, cleaned and concentrated on Strata-X reversed phase column (Phenomenex). The extracts were evaluated on an HPLC, and then tested using a serial dilution method. Commercially available ergonovine (EN), ergocorine (ER), bromocryptine (BC) and ergocryptine (EC) were tested individually using 0 to 44 nM concentrations. Seed extract of E+ produced a significant (P P < 0.05) dose dependent manner with EC being most potent, followed by ER, BC, and then EN (70%, 40%, 30% and 10% at 44 nM concentration). The similarity of the inhibition curves of seed extract to that of the commercially available ergot alkaloids suggests a related mode of action and that the use of such ergot alkaloids and CYP3A4 assay is a good model to study the toxicity of tall fescue. Furthermore, it provides the foundation to identify the individual toxic components of purified endophyte infected tall fescue extract.

Phytochemical Profiling with Antioxidant and Antimicrobial Screening of <i>Amaranthus viridis</i>L. Leaf and Seed Extracts

Methanol extracts of the dried leaves and seeds of Amaranthus viridis were collected and used for phytochemicals and antibacterial analysis. By detecting the MIC and zone inhibition, the antibacterial activity was determined against different bacterial and fungal strains. The extract yields from the leaves and seeds ranged 5.5-6.1 and 2.42%-3.72% w/w, respectively. Phytochemical investigation of this plant determines that tanins (6.07%-5.96%), saponins (53%-32%), alkaloids (13.14% - 11.42%), protiens (16.76%-24.51%) and glycosides (63.2%-32.3%) were rich in leaves. The extracts also contained appreciable levels of total phenolic contents (2.81-3.61 GAE, g/100 g), total flavanoid contents (18.4-5.42 QE, g/100 g) and DPPH free radical scavenging activity, showing IC50 (83.45-75.95 μg/mL) along with reducing power was calculated. The MIC of extracts ranged 178 - 645 μg/mL. The results of this study suggest the possibility of using the methanolic extracts in treating the diseases caused by the test organisms.

Effects of <i>Nigella sativa</i>L. Seed Extract on Fatigue, Blood Biochemical Parameters and Thyroid Function in Male Mice

Nigella sativa L. (Black seed), is a traditional herbal medicine that has been used for many purposes. The present study was designed to investigate the effects of hydro-alcoholic extract of nigella sativa L. (NS) on performance of Forced Swimming Test (FST), blood biochemical parameters related to fatigue and thyroid functions. Therefore, Blood Urea Nitrogen (BUN), Creatine Kinase (CK), Lactic Dehydrogenase (LDH), and Total Protein (TP), triiodothyronine T3, thyroxin T4 and TSH tests were investigated. Thirty five male adult mice were randomly divided into five groups: three NS-fed groups, one fluoxetine treated group and one control group. Three NS experimental groups received hydro-alcoholic extract of NS at doses of 50, 100 and 200 mg/kg orally for two weeks. Immobility time decreased in all NS groups compared with control group. Administration of NS significantly increased the concentration of T3 and T4 of the treatment groups. On the contrary, the amount of BUN, CK, LDH, TP and TSH decreased. In conclusion, black seed extract at the experimented doses showed anti-depressant, anti-fatigue and hyperthyroid effects.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells

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 Th17and the inflammatory factors such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6, IL-12, IL-17and 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-1β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide(P<0.01), inhibited the secretion of TNF-α, IL-1β, 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.

Buffalo stirred yoghurt fortified with grape seed extract:New insights into its functional properties

Grape seed extract(GSE)is considered one of the major byproducts,which are rich in phenolic content and possess several health-promoting activities including antibacterial,anticancer,and antioxidant.The current research was devoted to improve the bioactive properties of stirred yoghurt through supplementation with GSE at three concentrations(0.1,0.25,and 0.5 g/100 g yoghurt).The obtained stirred yoghurts were analyzed for determining their composition,pH,syneresis,viscosity,and sensory evaluation.Furthermore,some functional properties including antioxidant,antibacterial,anticancer activities were estimated.Significant increments(p≤0.05)were observed in total solids,ash contents,pH,water holding capacity,and viscosity values,especially when 0.5%GSE was added.Moreover,adding 0.5%GSE showed higher(p≤0.05)in vitro antioxidant,antibacterial,and anticancer activities.Interestingly,the improved bioactive properties resulting from adding GSE,even at the higher concentration,were not accompanied by any change in sensory properties.In particular,the color descriptor was mostly preferred by panelists when 0.5%GSE was added.The assessors did not observe any off-flavors in any of the tested stirred yoghurt samples.Therefore,the functional properties of stirred yoghurt could be improved by adding GSE preparation without affecting its organoleptic properties.

Transcriptome profile and its partly verification of human hepatocellular carcinoma cells exposed to Yuzhizi(Fructus Akebiae Quinatae) seed extract

OBJECTIVE: To investigate the efficacy of Yuzhizi(Fructus Akebiae Quinatae) seed extract(FAQSE) on inhibiting the proliferation of hepatocellular carcinoma(HCC) cells in vitro and to explore the anti-HCC action mechanism of FAQSE. METHODS: Human HCC Hep G2 and Huh7 cells were used to investigate the anti-HCC effect of FAQSE in vitro. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide(MTT) method was used to measure cell viability. Affymetrix microarray was adopted to detect the expression of transcriptome. The differentially expressed genes(DEGs) of each cell line were identified. For coDEGs of both cell lines, the gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway were enriched using the Database for Annotation, Visualization and Integrated Discovery(DAVID), and the network analysis of protein-protein interaction(PPI) was mapped using the Retrieval of Interacting Genes/Proteins(STRING) and Cytoscape software. Some important genes in the PPI network of coDEGs were selected to verify by quantitative real-time reverse transcription-polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay. RESULTS: FAQSE decreased the viability of Hep G2 and Huh7 cells. There were 211 co-upregulated and 86 codownregualted genes in both cell lines after FAQSE treatment. The enriched GO terms of co-upregulated DEGs were primarily involved cell-cell adhesion, viral process, transcription initiation from RNA polymerase II promoter, positive regulation of transcription from RNA polymerase II promoter and actin cytoskeleton organization. The GO terms of co-downregulated DEGs were mainly enriched in the processes of SRP-dependent cotranslational protein targeting to membrane, viral transcription, nuclear-transcribed m RNA catabolic process, nonsense-mediated decay, translational initiation and r RNA processing. Main KEGG pathways of co-upregulated DEGs were endocytosis, glutathione metabolism, protein processing in endoplasmic reticulum, synaptic vesicle cycle and lysosome. The major KEGG pathways of co-downregulated DEGs were ribosome, biosynthesis of amino acids, arginine and proline metabolism, systemic lupus erythematosus and complement and coagulation cascades. The top 10 coDEGs with high hub nodes in STRING analysis were ribosomal protein S27a, transferrin, ribosomal protein S20, ribosomal protein L9, protein phosphatase 2 regulatory subunit B alpha, transthyretin, thioredoxin reductase 1, ribosomal protein L3, ribophorin I and ribosomal protein L24. Alpha-fetoprotein(AFP) was also co-downregulated and contained in the PPI network. The m RNA and protein expression of most verified genes was consistent with the results of co-DEGs analysis. And the AFP level was significantly reduced after FAQSE treatment. CONCLUSIONS: A series of genes and pathways of Hep G2 and Huh7 cells were changed after FAQSE treatment, which might be the targets of FAQSE against HCC and worthy of further study. AFP might be important one of them.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage： normal saline solution （control）; arsenic trioxide （ATO; 4 mg/kg）; GSPE （400 mg/kg）; ATO＋GSPE （100 mg/kg）; ATO＋GSPE （200 mg/kg） and ATO＋GSPE （400 mg/kg）. Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor （erythroid-derived 2）-like 2 （Nrf2）, heme oxygenase 1 （HO1）, glutathione S-transferase （GST）, NAD（P）H dehydrogenase, and quinone 1 [NQO1） expression in the testis was detected by real-time PCR. Superoxide dismutase （SOD）, glutathione （GSH）, total antioxidative capability （T-AOC）, malondialdehyde （MDA）, 8-hydroxydeoxyguanosine （8-OHdG）, and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO ＋GSPE group showed recovery of the measured parameters. Mice treated with ATO＋high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NO.O1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

Inhibitory Effects of Grape Seed Proanthocyanidin Extract on Selenite-induced Cataract Formation and Possible Mechanism

This study investigated the inhibitory effect of grape seed proanthocyanidin extract(GSPE) on selenite-induced cataract formation in rats and the possible mechanism.Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups:control group,model group,three GSPE groups(low dose,medium dose and high dose).Control group received subcutaneous injection of physiological saline.Model group was given subcutaneous injection of sodium selenite(20 μmol/kg body weight) on the postpartum day 10,and once every other day for consecutive three times thereafter.GSPE treated groups were respectively administered GSPE at doses of 50,100,and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection(that was,on the postpartum day 8),and once daily for fourteen consecutive days thereafter.The opacity of lenses was observed,graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured.The lenses were analyzed for superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-PX),malondialdehyde(MDA),calcium(Ca 2+),nitric oxide(NO) and anti-hydroxyl radical ability(anti-OH).The histomorphology of lenses was observed with HE staining under a light microscope.The levels of calpainⅡ,and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR.The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group,and the achievement ratio of model group was 100%.As compared with model group,the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups.Moreover,we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes(SOD,CAT,GSH-PX) and anti-OH ability,accompanied by a significant increase in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.Administration of GSPE could dose-dependently preserve the activities of these antioxidative enzymes and anti-OH ability,accompanied by a significant reduction in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.These results suggested that GSPE markedly prevented selenite-induced cataract formation probably by suppressing the generation of lipid peroxidation and free radicals as well as the activation of iNOS,and calpainⅡ in the lenses.

Neuroprotective Effects of Grape Seed Procyanidin Extracton Ischemia-Reperfusion Brain Injury

Objective Oxidative stress （OS） plays a crucial role in ischemic stroke. Grape seed procyanidin extract （GSPE） was reported to be a critical regulator of OS. We hypothesized that GSPE might also be protective in ischemia-reperfusion brain injury. This study aimed to explore whether GSPE administration can protect mice from ischemia-reperfusion brain injury. Methods Transient middle cerebral artery occlusion （MCAO） was conducted followed by reperfusion for 24 hours to make ischemia-reperfusion brain injury in mice that received GSPE （MCAOG, n=60） or normal saline （MCAONS, n=60）. Sham-operated mice （GSPE group and normal saline group） were set as controls. The neurological severity score （NSS） was used to evaluate neural function impairment 1 hour, 24 hour, 3 days and 7 days after MCAO. Mice underwent brain T2WI imaging with a 3T animal MRI scanner 24 hours after reperfusion, and the stroke volume of brains were calculated according to abnormal signal intensity. Immunohistopathological analysis of brain tissues at 24 h after reperfusion was performed for neuronal nuclear antigen （NeuN）, CD34, Bcl-2, and Bax. Glutathione peroxidation （GSH-Px） activity and the level of malonaldehyde （MDA） of brain tissue were also examined. The above indexes were compared among the groups statistically.Results Significant functional improvement was observed 24 hours after MCAO in MCAOG group compared to MCAONS group （P〈0.05）. MCAOG group had smaller cerebral stroke volume （22.46 ± 11.45 mm3 vs. 47.84±9.06 mm3, P〈0.05） than MCAONS group 24 hours after MCAO. More mature NeuN-immunoreactive neurons and more CD34-positive cells in peri-infarct zones were observed in brain tissue of MCAOG mice 24 h after MCAO than that of MCAONS mice （both P〈0.05）. MCAONS mice had significantly higher number of Bax-positive cells in brain tissue than MCAOG （P〈0.05）. The mean MDA level was significantly lower （P〈0.05） and the GSH-Px activity was significantly higher （P〈0.05） in brains of MCAOG mice compared to those of MCAONS mice. Conclusion GSPE administration protects mice from ischemia-reperfusion brain injury through attenuating oxidative stress and apoptosis, promoting angiogenesis, and activating antioxidant enzyme GSH-Px. GSPE may represent a new therapeutical direction for the treatment of ischemia-reperfusion brain injury.