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The ability of a specially prepared water propolis extract (PWE) to preserve the functional activity of the intestinal mucosa after radiation exposure was studied. PWE was given orally (650 mg/kg) to rats five days prior to irradiation by 6 Gy and continued for further two days. Rats were sacrificed 24 h later, intestinal segments were examined histologically and homogenates were used to assess relevant biochemical parameters reflecting intestinal injury. Irradiation led to a rise in the histological damage score, a rise in tissue TNF-α and TBARS, and a decrease in sucrase, alkaline phosphatase, GSH and cholecystokinin as well as a decrease in plasma citrulline. The findings reflect a decrease in intestinal functional activity. PWE preserved the intestinal integrity and largely protected against the changes induced in the histology damage score and all parameters measured, possibly as a result of the antioxidant and anti-inflammatory action of its caffeic acid content. [ABSTRACT FROM AUTHOR]

Purpose: STW 5 (marketed as Iberogast®, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory properties and antioxidant activity. We investigated the effect of STW 5 against intestinal injury induced after whole body exposure to ionizing radiation (IR). Materials and methods: Intestinal mucositis was induced in rats by irradiation at a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were tested to assess biochemical parameters indicating intestinal injury and jejunum segments were exposed to semi-quantitative histological examination. Results: IR led to an increase in overall damage severity (ODS) score associated with a significant rise in tumor necrosis factor (TNF-α) and thiobarbituric acid reactive substances (TBARS) by 46% and 50% ( p ≤ 0.05), respectively, whereas the reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities were significantly decreased by 68%, 76% and 25% ( p ≤ 0.05), respectively, in intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment with STW 5 guarded against the changes in ODS score and in all parameters measured. Conclusion: Pre-treatment with STW 5 has the potential to decrease the severity of radiation-induced mucositis. [ABSTRACT FROM AUTHOR]

Background: Exposure to stress has been related to disturbance in 5‐hydroxytryptamine (5‐HT) signaling in the brain‐gut axis and is considered as a major predisposing factor for the development of irritable bowel syndrome (IBS). The present study aimed to investigate the possible involvement of 5‐HT and some other stress‐related parameters in the effectiveness of STW 5 against stress‐induced IBS. Methods: Rats were subjected to restraint stress (RS) for 1 h/day for 14 consecutive days to induce IBS‐like symptoms and were given STW 5 orally at the same time. At the end of the experiment, blood samples were withdrawn, then animals were euthanized and the brain hippocampi, cerebral cortices, as well as colons were isolated for biochemical and histopathological assessments. Results: RS increased the plasma corticotrophin releasing factor (CRF) with concomitant increase in hippocampal and cortical 5‐HT levels, as well as mast cell inflammatory mediators, oxidative stress biomarkers, and histopathological inflammatory changes observed in rat colon. It also decreased the colonic content of 5‐HT with consequent decrease in fecal pellet output (FPO). Treatment with STW 5 protected against these changes. Conclusion: The protective effect of STW 5 against RS‐induced IBS is related to its ability to normalize the induced changes in 5‐HT in the brain‐gut axis and counteract the stress‐induced oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) patients frequently suffer from depressive disorders as well. The present study was carried out to explore whether treatment with a standardized rice bran extract (RBE) could affect depression-like behavior in rats with dextran sulfate sodium (DSS)-induced colitis. Male Wistar rats were treated with RBE (100 mg/kg/day; p.o.) for 2 weeks. During the second week, colitis was induced by feeding the rats with 5 % (w/v) DSS in drinking water. RBE protected against DSS-induced body weight loss as well as against the macro- and microscopic inflammatory changes of the colon. Additionally, RBE mitigated DSS-induced dysregulation in blood–brain barrier tight junctional proteins, preserved the hippocampal histopathological architecture and improved the animal behavior in the forced swimming test. This was associated with modulation of hippocampal oxidative stress marker; GSH as well as hippocampal pro-inflammatory mediators; NF-ĸB and IL-1β. Treatment with RBE also led to a profound increase in the hippocampal levels of Sirt1, PGC-1α, Nrf2, and HO-1, which were drastically dropped by DSS. In conclusion, the study revealed the protective effect of RBE against DSS-induced depressive-like behavior through modulation of different parameters along the gut-brain axis and up-regulated the Sirt1/PGC-1α/Nrf2/HO-1 signaling pathway. [Display omitted] • Rice bran extract (RBE) mitigates DSS-induced depressive-like behavior. • RBE prevented DSS-induced disruption of blood-brain barrier. • RBE mitigates DSS-induced neuronal oxidative stress and inflammation. • RBE modulates different parameters along the gut-brain axis. • RBE up-regulates hippocampal Sirt1/PGC-1α/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of aqueous propolis extract (AEP) against indomethacin (Indo)-induced gastric ulcers in irradiated and non-irradiated rats. Materials and methods: Animals were irradiated at different radiation dose levels before the induction of ulcers. AEP was injected orally 1 hour before induction of gastric ulcers and the effects compared with those of lansoprazole (Lanso), which was used as a reference anti-ulcerogenic drug. Results: Pretreatment of rats, either irradiated or non-irradiated, with AEP effectively protected against Indo-induced gastric ulceration. This was associated with a reduction in acid output and peptic activity and an increase in the secretion of mucin. The mucosal prostaglandin E2 (PGE2) level was also increased. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were suppressed to the same extent after treatment. Both propolis and Lanso were effective in reducing the number of gastric lesions as well as the plasma level of malondialdehyde (MDA). Conclusions: These findings indicate that the gastroprotective effect of AEP could be of value in the management of excessive gastric damage induced by radiation exposure. [ABSTRACT FROM AUTHOR]

Purpose: Cartilage degradation usually results as a consequence of inflammatory processes in the joints. To study this phenomenon experimentally, adjuvant-induced arthritis ((AIA)) was used as a model of chronic inflammation under the influence of irradiation. The potential chondroprotective effect of 13%% aqueous extract of propolis ((AEP)) in arthritic rats was investigated. Materials and methods: The influence of whole body irradiation on the arthritic inflammatory response was investigated by subjecting rats to a Gamma source before the induction of arthritis. 13%% AEP was injected intraperitoneally in a dose of 5 ml//kg and diclofenac was used as reference non-steroidal anti-inflammatory drug ((NSAID)) in a dose of 3 mg//kg. The chosen parameters for cartilage integrity were glycosaminoglycan ((GAG)), hydroxyproline contents in cartilage and cartilage oligomeric matrix protein ((COMP)) in serum. The serum levels of tumour necrosis factor-alpha ((TNF-αα)), nitric oxide ((NO)) and the oxidative stress biomarkers such as blood glutathione ((GSH)) and plasma malondialdehyde ((MDA)) levels. Results: Induction of arthritis led to a reduction in GAG and hydroxyproline content of femoral cartilage and a corresponding rise in COMP in serum. Previous exposure to irradiation resulted in a milder reduction of GAG and hydroxyproline and a lesser rise in COMP. Treatment of arthritic irradiated and non-irradiated rats with 13%% AEP markedly prevented the breakdown of cartilage in a much more effective manner than diclofenac. Both AEP and diclofenac were equipotent in reducing the level of TNF-αα and were able to normalize NO and the oxidative stress biomarkers in non-irradiated and irradiated arthritic rats. Conclusion: The ability of propolis to protect cartilage degradation could therefore prove of value in the treatment of chronic arthritic diseases, offering an advantage over some NSAID, particularly those with a potential detrimental effect on cartilage integrity. [ABSTRACT FROM AUTHOR]

Depression is one of the common neurological comorbidities in patients with inflammatory bowel disease (IBD). The current study aimed to investigate the potential impact of niacin on colitis-induced depressive-like behavior in rats. Animals were given 5 % dextran sulfate sodium (DSS) in drinking water for one week to induce colitis. Niacin (80 mg/kg), with or without mepenzolate bromide (GPR109A blocker), was administered once per day throughout the experimental period. Rats were tested for behavioral changes using open field and forced swimming tests. Niacin significantly ameliorated DSS–induced behavioral deficits and alleviated macroscopic and microscopic colonic inflammatory changes. It also augmented the hippocampal levels of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the blood-brain barrier (BBB) integrity. Moreover, niacin decreased hippocampal IL-1ꞵ and NF-ĸB contents but increased GSH, Sirt-1, Nrf-2, HO-1 concentrations. All these beneficial effects were partially abolished by the co-administration of mepenzolate bromide. The neuroprotective effect of niacin against DSS-induced depressive-like behavior was partially mediated through GPR109A-mediated mechanisms. Such mechanisms are also involved in modulating neuronal oxidative stress and inflammation via Sirt-1/Nrf-2/HO-1 signaling pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD. [ABSTRACT FROM AUTHOR]

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein–coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1–3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1–3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial dysfunction plays a major role in the development of age-related neurodegenerative diseases and recent evidence suggests that food ingredients can improve mitochondrial function. In the current study we investigated the effects of feeding a stabilized rice bran extract (RBE) on mitochondrial function in the brain of guinea pigs. Key components of the rice bran are oryzanols, tocopherols and tocotrienols, which are supposed to have beneficial effects on mitochondrial function. Concentrations of α-tocotrienol and γ-carboxyethyl hydroxychroman (CEHC) but not γ-tocotrienol were significantly elevated in brains of RBE fed animals and thus may have provided protective properties. Overall respiration and mitochondrial coupling were significantly enhanced in isolated mitochondria, which suggests improved mitochondrial function in brains of RBE fed animals. Cells isolated from brains of RBE fed animals showed significantly higher mitochondrial membrane potential and ATP levels after sodium nitroprusside (SNP) challenge indicating resistance against mitochondrial dysfunction. Experimental evidence indicated increased mitochondrial mass in guinea pig brains, e.g. enhanced citrate synthase activity, increased cardiolipin as well as respiratory chain complex I and II and TIMM levels. In addition levels of Drp1 and fis1 were also increased in brains of guinea pigs fed RBE, indicating enhanced fission events. Thus, RBE represents a potential nutraceutical for the prevention of mitochondrial dysfunction and oxidative stress in brain aging and neurodegenerative diseases. [Copyright &y& Elsevier]

Purpose: The potential value of celecoxib was compared to a standard non-steroidal anti-inflammatory drug (NSAID), diclofenac in the adjuvant-induced arthritis (AIA) model in rats as a model of chronic inflammation under the influence of ionising radiation. Material and methods: Various inflammatory mediators and biochemical parameters were measured in the arthritic rats under the influence of ionising radiation. Results: Exposure of the animals to a radiation dose of 2 Gy before inoculation of the adjuvant led to a marked increase in the paw volume reaching ca. 70% more than that in non-irradiated ones as well as a significant increase in the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) as an index of cyclooxygenase-2 (COX-2) activity, thromboxane B2 (TXB2) as an index of cyclooxygenase-1 (COX-1) activity and plasma level of malondialdehyde (MDA). The blood glutathione (GSH) level was not affected by the dose of irradiation used while superoxidedismutase (SOD) activity was reduced. Treatment with celecoxib in a dose of 5 mg/kg was effective in decreasing the elevated levels of IL-6, IL-1β, TNF-α, PGE2 whereas it lacked any effect on TXB2 level since it had hardly any effect on COX-1 enzyme. Both drugs at the selected dose levels showed no effect on level of MDA, GSH and SOD activity. Conclusion: Irradiation of animals caused a marked change in the inflammatory response in AIA model of inflammation. Both celecoxib and diclofenac were nearly equipotent in suppressing the inflammatory response in both normal and irradiated rats. Accordingly, since the inhibition of COX-1 by traditional NSAID is thought to have undesirable side-effects on proliferating tissues, it would seem preferable to use selective COX-2 inhibitors to limit such deleterious effect. [ABSTRACT FROM AUTHOR]

Abstract: The major limiting factor in long-term administration of doxorubicin is the development of cumulative dose-dependent cardiomyopathy and congestive heart failure that limit the use of this drug. The present study was undertaken to find out the chemo protective role of methimazole against doxorubicin-induced cardiotoxicity in experimental animals. In the present study, doxorubicin treatment in a dose of 3mg/kg, i.p., every other day for six doses showed a significant 2.6-, 3- and 10.5-fold increase in the cardiac enzyme activities CK-MB and LDH and troponin-I, respectively, in the serum of the animals. Histopathological investigation of heart tissues showed swollen muscle fibers with interstitial edema and inflammatory exudate. Pretreatment of the animals with methimazole at a dose level of 40mg/kg, i.p., 30min before doxorubicin, returned the cardiac enzyme levels to nearly normal value with partial reversal of the inflammatory lesions and the swollen muscle fibers induced by doxorubicin. Moreover, methimazole pretreatment, decreased the doxorubicin level in the heart tissues with a significant increase in plasma level and non significant effect on doxorubicin level in tumor cells. At the same time, methimazole pretreatment did not significantly interfere with the antitumor activity of doxorubicin. [Copyright &y& Elsevier]

Solanum indicum ssp. distichum is used as a vegetable in some parts of Africa and claimed in folk medicine to guard against cardiovascular disorders. It was of interest to study the potential blood pressure lowering effects of a standardized extract of the fruit. An ethanolic extract of the fruit, standardized to contain > 0.15% chlorogenic acids, was tested orally in both normotensive rats and in those rendered hypertensive by twice daily intraperitoneal injection of NW-nitro-l-arginine methylester (l-NAME) for 1 week. The extract was either given at the same time asl-NAME or after the establishment of hypertension. The systolic blood pressure (SBP) was measured non-invasively using a tail cuff computer-aided monitoring device. Treatment of normotensive rats with the extract (30–300 mg/kg) for 4 weeks showed no hypotensive effect. Giving the extract (100 and 300 mg/kg) orally once daily during the 1 week hypertension induction period withl-NAME prevented the development of hypertension. Administration of the extract orally for 1 week after the establishment of hypertension tended to normalize the blood pressure. Pharmacological evidence for the antihypertensive activity of S. distichum is hereby reported for the first time. The extract showed good prophylactic as well as curative effect againstl-NAME-induced hypertension, whereby its content of chlorogenic acids may play a minor role. Other constituents may be responsible for the antihypertensive action. The findings support further development of the extract as a potential therapeutically useful antihypertensive agent. [ABSTRACT FROM AUTHOR]