pinosylvin and Disease-Models--Animal

Two synthesized resveratrol analogs from our laboratory, namely pinosylvin (3,5-dihydroxy-trans-stilbene, PIN) and 4,4'-dihydroxystilbene (DHS), have been carefully evaluated for treatment of oligoasthenospermia. Recent studies have demonstrated that PIN and DHS improved sperm quality in the mouse. However, the mechanism of action of PIN and DHS on oligoasthenospermia remains unknown. Herein, we investigated the mechanistic basis for improvements in sperm parameters by PIN and DHS in a mouse model of oligoasthenospermia induced by treatment with busulfan (BUS) at 6 mg/kg b.w.. Two weeks following busulfan treatment, mice were administered different concentrations of PIN or DHS daily for 2 consecutive weeks. Thereafter, epididymal sperm concentration and motility were determined, and histopathology of the testes was performed. Serum hormone levels including testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured using corresponding specific enzyme-linked immunosorbent assay (ELISA) kits. Testicular mRNA expression profiles were determined by RNA sequencing analysis. These findings were validated by quantitative real-time PCR, western blotting and ELISA. Both PIN and DHS improved the epididymal sperm concentration and motility, enhanced testosterone levels, and promoted testicular morphological recovery following BUS treatment. PIN treatment was found to significantly reduce oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE)-dependent antioxidant, glutathione peroxidase 3. DHS treatment significantly reduced oxidative stress via the Nrf2-ARE-dependent antioxidants glutathione S-transferase theta 2 and glutathione S-transferase omega 2. In summary, PIN and DHS ameliorated oligoasthenospermia in this mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.

Topics: Animals; Antioxidant Response Elements; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred ICR; Molecular Structure; NF-E2-Related Factor 2; Oligospermia; Oxidative Stress; Stilbenes; Structure-Activity Relationship

Insulin resistance is a characteristic finding in hyperglycaemia and type 2 diabetes. SIRT1 is a NAD

Topics: AMP-Activated Protein Kinases; Animals; Biological Transport; Carbohydrate Metabolism; Cell Culture Techniques; Diabetes Mellitus, Type 2; Disease Models, Animal; Energy Metabolism; Glucose; Glucose Transporter Type 4; Heterocyclic Compounds, 3-Ring; Insulin; Insulin Resistance; Lactones; Muscle, Skeletal; Myoblasts; Organelle Biogenesis; Phytochemicals; Rats; Signal Transduction; Sirtuin 1; Stilbenes

Hovenia dulcis Thunb. (Rhamnaceae) is a hardy tree native to Europe, the Middle East, and North Africa, and it is also grown in parts of Asia and has been used in traditional medicine to treat liver toxicity, stomach disorders, and inflammation. This study investigated the anti-allergy potential of an extract of the branches of H. dulcis (HDB) using the antigen-stimulated mast cell-like cell line rat basophilic leukemia (RBL)-2H3 and a passive cutaneous anaphylaxis (PCA) mouse model. Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses, and PCA were performed to measure allergic responses and proinflammatory mediators in antigen-stimulated rat basophilic leukemia (RBL)-2H3 mast cells and the PCA mouse model. In antigen-stimulated RBL-2H3 cells, HDB inhibited the secretion of β-hexosaminidase (indicating the inhibition of degranulation) and histamine release; decreased expression and production of the inflammatory mediators, cyclooxygenase-2 and prostaglandin E2, and cytokines interleukin-4 and tumor necrosis factor-α; and suppressed activation of nuclear factor κB, a transcription factor involved in the response to cytokines. HDB attenuated phosphorylation of the mast cell downstream effectors Lyn, Syk, phospholipase Cγ, protein kinase Cμ, extracellular signal-regulated kinase and p38. In IgE-sensitized mice, HDB inhibited mast cell-dependent PCA. Furthermore, HDB contained pinosylvin and possessed significant anti-allergic activities. These results suggest that HDB would be of value in the prevention and treatment of allergic diseases.

Topics: Animals; Anti-Allergic Agents; beta-N-Acetylhexosaminidases; Cell Line, Tumor; Cell Survival; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Hypersensitivity; Immunoglobulin E; Interleukin-4; Mast Cells; Mice; Mice, Inbred BALB C; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Passive Cutaneous Anaphylaxis; Plant Extracts; Rats; Rhamnaceae; Signal Transduction; Stilbenes; Tumor Necrosis Factor-alpha

The aim of this study was to evaluate the effects of pinosylvin (PIN) and pterostilbene (PTE), natural substances from the stilbenoid group, on the development of adjuvant arthritis in rats.. Adjuvant arthritis (AA) was induced by a single intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in male Lewis rats. Our experiments included healthy intact animals as reference controls, arthritic animals without any drug administration, and arthritic animals with administration of PIN and PTE in the oral daily dose of 30 mg/kg b.w. The treatment involved administration of the substances tested from day 0, i.e. the day of immunization, to the experimental day 28. The following parameters were monitored: change of the hind paw volume (HPV) on day 14, 21 and 28, luminol-enhanced chemiluminescence (CL) of the joint and myeloperoxidase (MPO) activity in hind paw joint homogenates (day 28).. Arthritic animals treated with PIN showed a decrease in HPV, significantly on days 14 and 28. PIN decreased CL of the joint as well as MPO activity of the joint homogenate, in comparison with untreated animals. PTE had no effect on HPV and MPO activity in hind paw joint homogenates and exerted only a partial effect on luminol-enhanced CL.. On the basis of our results we conclude that the effect of PTE on CL was only partial. PIN, on the other hand, had a beneficial anti-inflammatory and antioxidant effect on oxidative stress induced biochemical changes occurring in AA, as determined by all three functional parameters.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Male; Oxidative Stress; Peroxidase; Rats; Rats, Inbred Lew; Reactive Oxygen Species; Stilbenes

Formation of reactive oxygen species in neutrophils of rats with adjuvant arthritis and generation of nitric oxide in RAW 264.7 macrophages were analysed in the presence of pinosylvin.. The method of chemiluminescence was used for the detection of reactive oxygen species in blood of rats with adjuvant arthritis. Pinosylvin (50 mg/kg, daily, p.o.) and methotrexate (0.4 mg/kg, twice a week, p.o.) were applied separately or in a combination over a period of 28 days from the day of immunisation. Adjuvant arthritis was accompanied by a significantly increased number of neutrophils, by elevated concentration of oxidants in blood and by excessive responsiveness of neutrophils to stimulation with PMA. In rats treated with methotrexate, all these changes were significantly reduced and the inhibition became more pronounced when methotrexate was applied in the combination with pinosylvin; the monotherapy with pinosylvin did not induce any detectable changes in the parameters tested. Under in vitro conditions, pinosylvin inhibited formation of nitric oxide (NO) in macrophages, as demonstrated by the decreased concentration of nitrite - the end-product of NO metabolism (assessed by Griess' method), by the reduced expression of inducible NO synthase (detected by Western blot), and by the failure of pinosylvin to scavenge nitric oxide (measured amperometrically in cell-free system).. The observed ability of pinosylvin to decrease concentration of reactive oxygen and nitrogen species, along with its capacity to enhance the efficacy of methotrexate in arthritis treatment may shed more light into the pharmacological potential of this prospective natural substance.

Topics: Animals; Antioxidants; Antirheumatic Agents; Arthritis, Experimental; Cell Line; Disease Models, Animal; Drug Therapy, Combination; Macrophages; Male; Methotrexate; Neutrophils; Nitric Oxide; Rats; Rats, Inbred Lew; Reactive Oxygen Species; Resveratrol; Stilbenes