Grape seed proanthocyanidin extract inhibits platelet-derived growth factor induced proliferation of airway smooth muscle cells / 中国小儿急救医学

Objective To explore the effect of grape seed proanthocyanidin extract(GSPE) on the proliferation of airway smooth muscle cells( ASMCs) induced by platelet-derived growth factor( PDGF) and the underlying molecular mechanism. Methods ASMCs of primary rat were cultured. MTT and flow cytom-etry were used to detect the cell proliferation activity and cell cycle distribution of ASMCs which were treated with PDGF and GSPE respectively. The expression levels of cyclin D1,extracellular regulated protein kinases ( ERK)1/2,p-ERK1/2 and β-actin protein in each group ASMCs were analyzed using western blotting assay after ERK1/2 inhibitor PD98059 intervention. Results Compared with control group,cell proliferative activ-ity,S phase fraction and the expression of cyclin D1 and p-ERK1/2 protein increased in PDGF induced group (P<0. 05). These effects induced by PDGF could be reversed by GSPE. PD98059 also could block PDGF induced higher expression of p-ERK1/2 and cyclin D1 proteins in rat ASMCs. Conclusion GSPE can inhib-it PDGF induced cell proliferation and via ERK1/2 signaling pathway in rat ASMCs,which provide a new way for treatment of bronchial asthma.

Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway

BACKGROUND/AIMS: Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. RESULTS: GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IκBα synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-κB (NF-κB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. CONCLUSIONS: Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF-κB signaling pathway.

Effect of grape seed proanthocyanidins on phenotype marker protein of renal cells in db/db mice / 临床与实验病理学杂志

Purpose To investigate the effect of grape seed proanthocyanidins on the phenotype-transforming marker protein expression of db/db renal cells in mice model of type 2 diabetes,and to explore the protective mechanism of grape seed extract on diabetic renal injury in db/db mice.Methods Male db/db diabetic mice were randomly divided into two groups:diabetic group (db/db group) and diabetic + grape seed proanthocyanidin extract group (db/db + GSPE).The same week-old male db/m mice was used as normal controls (db/m) and grape seed proanthocyanidin extract gavage treatment group (db/m +grape seed proanthocyanidin extract group,db/m + GSPE).The mice of db/db + GSPE group and db/m + GSPE group were administered daily with grape seed proanthocyanidin extract (5mg/kg) by gavage.Results Renal tissues of db/db diabetic mice showed increased expression of α-SMA,p-p38MAPK,pERK1/2 and 8-OHdG level,and down-regulation in E-cadherin expression compared with db/m group (P ＜ 0.05).However,the alternations of α-SMA,p-p38,p-ERK1/2,E-cadherin protein levels,and 8-OHdG level,in db/db group were reversed by addition of grape seed proanthocyanidin extract (P ＜ 0.05).Conclusion Grape seed proanthocyanidin extract inhibits the epithelial to mesenchymal transition (EMT) associated protein,by decreasing ROS production,and activating p38 MAPK and ERK1/2.These findings suggest that grape seed proanthocyanidin extract provides a treatment option for diabetic nephropathy.

Effects of grape seed proanthocyanidin extract on airway inflammation and Treg/Th17 balance in asthmatic mice / 国际儿科学杂志

Objective To explore effect of grape seed proanthocyanidin extract (GSPE)on airway inflammation and hyperresponsiveness of ovalbumin-induced murine asthma model and the associated regulatory effect on Treg/Th17 imbalance.Methods A total of 40 mice were randomly assigned to four experimental groups:control,asthma model,low dose GSPE (40 mg/kg),and high dose GSPE (80 mg/kg).Acute asthma model was established with OVA;airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument;lung inflammation changes were observed by pathological HE staining;Treg/Th17 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA;the expressions of forkhead/winged helix transcription factor(Foxp3) mRNA and retinoid-related orphan receptor gammat (RORγt) mRNA in lung tissue of each group were gained by Real-time PCR method.Results GSPE inhibited ovalbumin-induced increases in airway responsiveness(P ＜ 0.05).Histological studies demonstrated that GSPE substantially inhibited OVA-induced airway inflammation in lung tissue.GSPE decreased IL-17A levels and increased IL-10 levels in bronchoalveolar lavage fluid (P ＜ 0.05).In the asthma model group,RORγt mRNA expression in lung tissue was significantly higher than that in the control group(P ＜ 0.05)and Foxp3 mRNA expression was significantly lower than that in the control group (P ＜ 0.05).In the GSPE group,RORγt mRNA expression was lower than that in asthma model group (P ＜ 0.05),however the Foxp3 mRNA expression was higher than that in asthma model group(P ＜ 0.05).Conclusion GSPE could alleviate airway hyperresponsiveness and airway inflammation of in asthmatic mice.It can modify the asthmatic mice Treg/Th17 imbalance by decreasing IL-17A and increasing IL-10 concentration at the level of cytokines;and also by increasing Foxp3 mRNA expression and inhibiting the expression of RORγt mRNA at the transcriptional level,which provide a new way for treatment of bronchial asthma.

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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, NQO1, and GST.</p><p><b>CONCLUSION</b>GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.</p>

Study on General Pharmacology of Grape Seed Proanthocyanidin Extract / 中国中医药信息杂志

Objective To investigate the influences of grape seed proanthocyanidin extract (GSPE) on cardiovascular system, nervous system and respiratory system of experimental animals, and provide general pharmacological data for further research and application. Methods The influences of GSPE on blood pressure, heart rate, electrocardiogram, breathing frequency and tidal volume in anesthetic dogs after duodenal administration were observed, the impacts on spontaneous activity, coordinated motion, and the sleep situation with threshold dose and subthreshold dose of pentobarbital sodium in mice after intragastric administration were observed. Results GSPE showed no side effects on blood pressure, heart rate, electrocardiogram, breathing frequency and tidal volume in anesthetic dogs at the dosage of 857.00, 214.29, 42.86 mg/kg (P>0.05). At the dosage of 428.57, 214.29, 42.86 mg/kg, GSPE had no obvious influence on spontaneous activities and coordinated movements in mice (P>0.05). GSPE did not evidently change the number of sleeping animals, the sleep latency and the sleeping duration with subthreshold dose and threshold dose of pentobarbital sodium (P>0.05). Conclusion GSPE has no evident adverse effects on central nervous system, cardiovascular system and respiratory system in animals.

Effects of Grape Seed Proanthocyanidin Extract on Peroxidation and Ability of Learning and Memory after Cerebral Ischemia/re-perfusion Injury in Rats / 中国康复理论与实践

Objective To investigate the effect of grape seed proanthocyanidin extract (GSPE) on learning and memory ability after cere-bral ischemia/reperfusion injury in rats and its mechanism. Methods 72 healthy male Sprague-Dawley rats were divided into sham group (n=18), model group (n=18) and GSPE groups (20 mg/kg, 200 mg/kg, n=18 for each group). The GSPE groups were administered GSPE orally for 4 weeks, while the sham group and model group were given water 10 ml/kg. Then their middle cerebral arteries were obstructed for 2 h and reperfused, excepted the sham group. 6 rats from each group were selected to test with Morris water maze 12 h, 24 h and 48 h after re-perfusion respectively. And then, their brain tissues were stained with Hematoxylin-Eosin staining to observe under optical microscope. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) in the brain tissues were measured. Results Compared with the sham group, the latency significantly prolonged, and the incidence of crossing the area the platform located reduced in the model group in the Mor-ris water maze test, with the SOD decreasing and MDA increasing (P<0.05). Compared with the model group, the latency reduced and the incidence of crossing the area increased in the GSPE 200 mg/kg group, with the SOD increasing and MDA decreasing (P<0.05). Conclu-sion GSPE may suppress peroxidation after the cerebral ischemia/reperfusion to protect brain and learning and memory ability from injury.

Effects of Grape Seed Proanthocyanidin Extract on Peroxidation and Ability of Learning and Memory after Cerebral Ischemia/reperfusionInjury in Rats / 中国康复理论与实践

@#Objective To investigate the effect of grape seed proanthocyanidin extract (GSPE) on learning and memory ability after cerebral ischemia/reperfusion injury in rats and its mechanism. Methods 72 healthy male Sprague-Dawley rats were divided into sham group (n=18), model group (n=18) and GSPE groups (20 mg/kg, 200 mg/kg, n=18 for each group). The GSPE groups were administered GSPE orally for 4 weeks, while the sham group and model group were given water 10 ml/kg. Then their middle cerebral arteries were obstructed for 2 h and reperfused, excepted the sham group. 6 rats from each group were selected to test with Morris water maze 12 h, 24 h and 48 h after reperfusion respectively. And then, their brain tissues were stained with Hematoxylin-Eosin staining to observe under optical microscope. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) in the brain tissues were measured. Results Compared with the sham group, the latency significantly prolonged, and the incidence of crossing the area the platform located reduced in the model group in the Morris water maze test, with the SOD decreasing and MDA increasing (P<0.05). Compared with the model group, the latency reduced and the incidence of crossing the area increased in the GSPE 200 mg/kg group, with the SOD increasing and MDA decreasing (P<0.05). Conclusion GSPE may suppress peroxidation after the cerebral ischemia/reperfusion to protect brain and learning and memory ability from injury.

Experiment study on anti-nonenzyme glycosylation effect of Grape Seed Proanthocyanidin Extract in Diabetic Rats / 中华老年医学杂志

0.05) during the experiment. The TC of middle dose GSPE group was marked ly different compared with that of normal group(P