METHODS: In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined.
RESULTS: Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only.
CONCLUSION: The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control.
METHODS: : Nulliparas with uncomplicated PROM at term, a Bishop score less than or equal to 6, and who required labor induction were recruited for a double-blind randomized trial. Participants were randomly assigned to 3-mg dinoprostone pessary and oxytocin infusion or placebo and oxytocin infusion. A cardiotocogram was performed before induction and maintained to delivery. Dinoprostone pessary or placebo was placed in the posterior vaginal fornix. Oxytocin intravenous infusion was commenced at 2 milliunits/min and doubled every 30 minutes to a maximum of 32 milliunits/min. Oxytocin infusion rate was titrated to achieve four contractions every 10 minutes. Primary outcomes were vaginal delivery within 12 hours and maternal satisfaction with the birth process using a visual analog scale (VAS) from 0 to 10 (higher score, greater satisfaction).
RESULTS: : One hundred fourteen women were available for analysis. Vaginal delivery rates within 12 hours were 25 of 57 (43.9%) for concurrent treatment compared with 27/57 (47.4%) (relative risk 0.9, 95% confidence interval 0.6-1.4, P=.85) for oxytocin only; median VAS was 8 (interquartile range [IQR] 2) compared with 8 (IQR 2), P=.38. Uterine hyperstimulation was 14% compared with 5.3%, P=.20; overall vaginal delivery rates were 59.6% compared with 64.9%, P=.70; and induction to vaginal delivery interval 9.7 hours compared with 9.4 hours P=.75 for concurrent treatment compared with oxytocin, respectively. There was no significant difference for any other outcome.
CONCLUSION: : Concurrent vaginal dinoprostone and intravenous oxytocin for labor induction of term PROM did not expedite delivery or improve patient satisfaction.
CLINICAL TRIAL REGISTRATION: : Current Controlled Trials, www.controlled-trials.com, ISRCTN74376345
LEVEL OF EVIDENCE: : I.
MATERIALS AND METHODS: The effects of mitragynine on the mRNA and protein expression of COX-1 and COX-2 and the production of prostaglandin E(2) (PGE(2)) were investigated in LPS-treated RAW264.7 macrophage cells. Quantitative RT-PCR was used to assess the mRNA expression of COX-1 and COX-2. Protein expression of COX-1 and COX-2 were assessed using Western blot analysis and the level of PGE(2) production was quantified using Parameter™ PGE(2) Assay (R&D Systems).
RESULTS: Mitragynine produced a significant inhibition on the mRNA expression of COX-2 induced by LPS, in a dose dependent manner and this was followed by the reduction of PGE(2) production. On the other hand, the effects of mitragynine on COX-1 mRNA expression were found to be insignificant as compared to the control cells. However, the effect of mitragynine on COX-1 protein expression is dependent on concentration, with higher concentration of mitragynine producing a further reduction of COX-1 expression in LPS-treated cells.
CONCLUSIONS: These findings suggest that mitragynine suppressed PGE(2) production by inhibiting COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Mitragynine may be useful for the treatment of inflammatory conditions.
METHODS: 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined.
RESULTS: Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT.
CONCLUSIONS: CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.
AIM OF THE STUDY: The present study aimed to characterize the chemical properties of a purified polysaccharide extracted from the aerial part of Tetrastigma hemsleyanum (SYQP) and investigate its antipyretic and antitumor effects in mice models.
MATERIALS AND METHODS: Water-soluble crude polysaccharides from the aerial parts of Tetrastigma hemsleyanum were extracted and fractionated by DEAE and gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, and FTIR analysis were performed to characterize the SYQP. Antipyretic effect of SYQP was examined using Brewer's yeast induced hyperthermia test. Antitumor effect was investigated using H22 tumor bearing mice. The serum cytokines were determined to evaluated the biological activities of SYQP.
RESULTS: SYQP was composed of galacturonic acid (GalA), glucose (Glc), mannose (Man), arabinose (Ara), galactose (Gal), and rhamnose (Rha) with a molar ratio of 11.3:7.1:2.5:1.0:0.9:0.5 and it had an average molecular weight of 66.2 kDa. The oral administration of SYQP at 200 and 400 mg/kg could markedly suppress the hyperthermia of mice induced by Brewer's yeast and decrease the production of cytokines especially prostaglandin E2 (PGE2) in the serum of mice. SYQP inhibited the growth of H22 tumor in mice with inhibitory rate of 39.9% at the administration dose of 200 mg/kg and increased the production of cytokines such as tumor necrosis factor-alpha (TNF-a) and interferon γ (IFN-γ). Experimental results showed that the preventive administration of SYQP before lipopolysaccharide (LPS) reduced the high cytokine levels such as IL-6, IL-10 and IFN-γ, indicating that SYQP might act as a competitor with LPS to interact with toll like receptor 4 (TLR4), which further regulated the secretion of cytokines.
CONCLUSION: The anti-inflammatory and antitumor activities of SYQP might be related to its regulation of host immune function by controlling the secretion of cytokines.
METHODS: The attenuating effects of syringin on the productions of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and the expressions of signaling molecules of the signaling pathways were investigated by using ELISA, Western blot, and qRT-PCR.
RESULTS: Syringin downregulated the NF-κB, MAPKs, and PI3K-Akt signal networks by significantly reducing PGE2 production in the macrophages via suppression of COX-2 gene and protein expression levels. It also reduced TNF-α and IL-1β secretion and their mRNA expression, suppressed phosphorylation of NF-κB (p65), IKKα/β, and IκBα, and restored ability of IκBα to degrade. Syringin dose-dependently attenuated Akt, p38 MAPKs, JNK, and ERK phosphorylation. Also, the expression of corresponding upstream signaling molecules toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) were down-regulated in response to syringin treatment.
CONCLUSION: The suppressive effect of syringin on the inflammatory signaling molecules in MyD88-dependent pathways suggested it's potential as a drug candidate for development into an agent for treatment of various immune-mediated inflammatory disorders.