The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.
Animals ; Arsenic ; toxicity ; Grape Seed Extract ; therapeutic use ; Inflammation ; chemically induced ; drug therapy ; Kidney Diseases ; chemically induced ; drug therapy ; Male ; Mice ; Proanthocyanidins ; therapeutic use

OBJECTIVETo investigate the protective effect of grape seed proanthocyanidin (GSP) on spermatogenesis following testicular torsion/detorsion in mice.

METHODSTwenty-four healthy male Kunming mice, aged 8 weeks and weighing 25 - 27 g, were randomly divided into a control, a torsion and a treatment group, each containing 8 animals. The unilateral testicular torsion/detorsion model was established in the treatment and torsion groups. Thirty minutes before detorsion, the animals of the treatment group were injected intraperitoneally with 50 mg/kg GSP, and those of the torsion group with normal saline at the same dose, both for 3 days postoperatively. On the 4th day after surgery, ipsilateral orchiectomy were performed to detect histopathological changes, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and the apoptotic index (AI) of germ cells in all the mice.

RESULTSCompared with the torsion group, the treated mice showed significantly increased Johnsen score (5.00 +/- 1.85 vs 7.38 +/- 0.92, P < 0.05), seminiferous tubule diameter ([176.50 +/- 1.60]microm vs [178.75 +/- 1.58] microm, P > 0.05), spermatogenic cell layers (3.75 +/- 1.03 vs 5.75 +/- 0.71, P < 0.05) and SOD activity ([29.04 +/- 4.46] U/mg prot vs [52.67 +/- 3.57] U/mg prot, P < 0.05), but remarkably reduced level of MDA ([4.63 +/- 0.05] nmol/mg prot vs [2.91 +/- 0.04] nmol/mg prot, P < 0.05) and AI of germ cells ([40.50 +/- 1.60]% vs [16.25 +/- 1.67] %, P < 0.05).

CONCLUSIONGrape seed proanthocyanidin has a protective effect against spermatogenic injury in mice, the mechanisms of which may be related to its actions of scavenging oxygen free radicals, inhibiting lipid peroxidation and improving the antioxidant ability of the body.

Animals ; Grape Seed Extract ; pharmacology ; therapeutic use ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred Strains ; Proanthocyanidins ; pharmacology ; therapeutic use ; Spermatic Cord Torsion ; drug therapy ; metabolism ; Spermatogenesis ; drug effects ; Superoxide Dismutase ; metabolism ; Vitis

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.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/pathology* ; Grape Seed Extract/therapeutic use* ; Interleukin-17 ; Interleukin-1beta ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Th1 Cells ; Mice, Inbred C57BL ; Interferon-gamma/therapeutic use* ; Th17 Cells/metabolism* ; Interleukin-12/therapeutic use* ; Cytokines/metabolism*