Phytochemicals as Modulators of Paraoxonase?1 in Health and Diseases

Chronic diseases such as cardiovascular disease (CVD), atherosclerosis, chronic liver disease, and neurodegenerative diseases are major causes of mortality. These diseases have gained much attention due to their complications, and therefore novel approaches with fewer side effects are an important research topic. Free radicals and oxidative stress are involved in the molecular mechanisms of several diseases. Antioxidants can scavenge free radicals and mitigate their adverse effects. One of the most important antioxidant enzymes are paraoxonases (PONs). These enzymes perform a wide range of physiological activities ranging from drug metabolism to detoxification of neuroleptics. Paraoxonase?1 (PON1) is produced in the liver and then transferred to the bloodstream. It has been demonstrated that PON1 could have beneficial effects in numerous diseases such as atherosclerosis, CVD, diabetes mellitus, and neurodegenerative diseases by modulating relevant signalling pathways involved in inflammation and oxidative stress. These pathways include peroxisome proliferator?activated receptor gamma (PPAR??) and protein kinase B/nuclear factor kappa?light?chain?enhancer of activated B cells (AKT/NF??B)?dependent signalling pathways. Increasing PON1 could potentially have protective effects and reduce the incidence of various diseases by modulating these signalling pathways. Several studies have reported that dietary factors are able to modulate PON1 expression and activity. This review aimed at summarizing the state of the art on the effects of dietary phytochemicals on PON1 enzyme activity and the relevant signalling pathways in different diseases

Beneficial Effects of Trachyspermum ammi (L.) Sprague on Rat Irritable Bowel Syndrome

Background and objective: Trachyspermum ammi (T. ammi) has been used for the treatment of various digestive disorders with considerable therapeutic effects such as anticholinergic and anti-oxidant activities.This study aimed to evaluate the efficacy of the hydro-alcoholic extract of the fruits of T. ammi in an experimental model of irritable bowel syndrome (IBS). Methods: The rats were classified into seven groups, including sham (no stress), control (saline recipients), loperamide and fluoxetine (10 mg/kg/day) (positive controls), and the plant groups at the doses of 150, 250 and 500 mg/kg/day for 5 days under restrictive stress, 2 days before receiving the treatment. All medicines were given as gavage. The effect of the plant extract on gastric emptying and the transit of the small intestine was evaluated. The levels of the inflammatory and oxidative related biomarkers, tumor necrosis factor alpha (TNF-α) and lipid peroxidation (LPO), also the myeloperoxidase (MPO) activity were measured. Results: The gastric emptying and the transit of the small intestine were significantly reduced in all T. ammi treated groups, and no significant difference was observed at the dose of 500 mg/kg/day compared with the loperamide group. The levels of TNF-α and MPO activities decreased in the treatment groups compared with the control, and the LPO level was decreased at the concentrations of 250 and 500 mg/kg/day compared to the control. The antioxidant levels significantly increased in the rats treated with T. ammi at the doses of 250 and 500 mg/kg/day. Conclusions: The severity of stress-induced IBS was reduced in a dose-dependent manner by the hydro-alcoholic extract of the fruits of T. ammi, confirming the effectiveness of this plant in the management of IBS.  </strong

Evaluation of phytochemicals, antioxidant and burn wound healing activities of Cucurbita moschata Duchesne fruit peel

Objective(s): Cucurbita moschata Duchesne (pumpkin) is a well-known plant with several pharmacological effects. The aim of the present study was to assess burn wound healing activity of C. moschata peel extract (CE). Also, standardized CE was assessed for antioxidant activity and antibacterial effects against major pathogens of burns. Materials and Methods: Healing properties of topical preparation of 10% and 20% concentrations of CE were assessed on second degree burn in rats during a 14-day period as well as histological studies, total antioxidant power, lipid peroxidation and total thiol content of skin tissue samples. Results: Radical scavenging IC50 and ferric-reducing antioxidant power value were 4.015±0.20 mg/ml and 142.63±2.65 mmol Fe2+/g, respectively. Total mucilage content was 13.8%. The optimal results were obtained by 20% CE that showed 90.80±5.86 % wound closure and tissue repair as well as significant reduction of tissue oxidative stress biomarkers. Histological analyses confirmed wound healing activity of pumpkin peel extract. Conclusion: Considering the high mucilage content of the plant, providing a moist environment for wound, C. moschata peel extract could be a natural remedy for treatment of burns. Further clinical studies are suggested to confirm C. moschata peel extract as a wound healing agent

Efficacy of Setarud (IMOD^®), a novel drug with potent anti-toxic stress potential in rat inflammatory bowel disease and comparison with dexamethasone and infliximab

219-226The inflammatory bowel disease (IBD) is an idiopathic, immune-mediated and chronic intestinal condition. In the present study, the effect of Serarud (IMOD®), a novel natural drug with known immunomodulatory, anti-inflammatory and antioxidant properties was investigated in experimental colitis in rats and compared with the dexamethasone and infliximab. Immunologic colitis was induced by intracolonic administration of a mixture of trinitrobenzene sulfonic acid (TNBS) and absolute ethanol in male Wistar rats. Animals were divided into 6 groups of sham (normal group), control (vehicle-treated), positive control (dexamethasone 1 mg/kg/day given orally and infliximab 5 mg/kg/day given subcutaneously) and 3 Setarud-treated groups (13.3, 20, 30 mg/kg/day given intraperitoneally). The treatment continued for 14 consecutive days and then animals were decapitated on the day 15 and distal colons were removed for macroscopic, microscopic, and biochemical assays. Biochemical markers, including TNF-, IL-1, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS) were measured in the homogenate of colonic tissue. A remarkable reduction in macroscopic and histological damage scores was observed in the animals treated with Setarud. These findings were confirmed by decreased levels of TNF-, interleukin-1, MPO activity and TBARS, and raised levels of FRAP in the colon tissue. These observations confirmed the immunomodulatory, anti-inflammatory and antioxidant properties of Setarud in experimental colitis, which was comparable to those of dexamethasone and infliximab

Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis: A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis (AP) or chronic pancreatitis (CP) and in the prevention of post-endoscopic retrograde cholangio-pancreatography (post-ERCP) pancreatitis (PEP) up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous. Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PEP. Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted

The involvement of JAK/STAT signaling pathway in the treatment of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder in which inflammation and oxidative stress play key etiopathological role. The pathology of PD brain is characterized by inclusions of aggregated α-synuclein (α-SYN) in the cytoplasmic region of neurons. Clinical evidence suggests that stimulation of pro-inflammatory cytokines leads to neuroinflammation in the affected brain regions. Upon neuroinflammation, the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway, and other transcription factors such as nuclear factor κB (NF-κB), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), mammalian target of rapamycin (mTOR), and toll-like receptors (TLRs) are upregulated and induce the microglial activation, contributing to PD via dopaminergic neuron autophagy. Aberrant activation or phosphorylation of the components of JAK/STAT signaling pathway has been implicated in increased transcription of the inflammation-associated genes and many neurodegenerative disorders such as PD. Interferon gamma (IFN-γ), and interleukine (IL)-6 are two of the most potent activators of the JAK/STAT pathway, and it was shown to be elevated in PD. Stimulation of microglial cell with aggregated α-SYN results in production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and IL-1β in PD. Dysregulation of the JAK/STAT in PD and its involvement in various inflammatory pathways make it a promising PD therapy approach. So far, a variety of synthetic or natural small-molecule JAK inhibitors (Jakinibs) have been found promising in managing a spectrum of ailments, many of which are in preclinical research or clinical trials. Herein, we provided a perspective on the function of the JAK/STAT signaling pathway in PD progression and gathered data that describe the rationale evidence on the potential application of Jakinibs to improve neuroinflammation in PD

Predicting etCO2 response in a model of ventilation-perfusion mismatch

BACKGROUND:Aluminum phosphide (AlP) is used as pesticide in some countries for protection of stored grains. Human poisoning with AlP due to suicide attempt or accidental environmental exposure is associated with very high mortality partially due to development of severe metabolic acidosis. Previous studies have shown that hemoglobin has high buffering capacity and erythrocytes can potentially be used for management of metabolic acidosis. The aim of this study was to evaluate the effect of fresh packed red blood cells (RBC) transfusion on survival and cardiovascular function in AlP-poisoned rats. METHODOLOGY/PRINCIPAL FINDINGS:Rats were poisoned with AlP by gavage. Fresh packed RBC was transfused via tail vein after AlP administration. Acid-base balance, vital signs and mortality was assessed and compared in experimental groups. Infusion of fresh packed RBC (1.5 ml) one hour after AlP (4-15 mg/kg) intoxication was associated with a significant decrease in mortality rate. Packed RBC infusion improved blood pH, HCO3-, Na+ and Ca2+ levels. Plasma troponin level was also reduced and ECG changes were reversed following packed RBC infusion in AlP intoxicated rats. CONCLUSIONS:Our results showed that fresh RBC transfusion could ameliorate metabolic acidosis and enhance survival in AlP-poisoned rat. We assume that an increase in pool of RBCs may modulate acid-base balance or potentially chelate AlP-related toxic intermediates via phosphine-hemoglobin interaction

Efficacy of topical application of standardized extract of Tragopogon graminifolius in the healing process of experimental burn wounds

Tragopogon graminifolius DC. is a perennial plant from the family Asteraceae which grows in West parts of Iran. Several biological activities like antimicrobial, antioxidant and anti-inflammatory effects are reported for the plant. The aim of this study was to assess the wound healing activity of standardized extract from T. graminifolius (TG) aerial parts. Topical standardized TG extract with 5% and 10% concentrations in eucerine base was assessed for its healing properties on second degree burn in rats during a 14-day period. Biomarkers of oxidative damage including total antioxidant power, lipid peroxidation and total thiol molecules of the skin tissue samples were also evaluated. Results showed that 10%TG had the best efficacy with 80 ± 3% wound closure and tissue repair in comparison to negative control (p < 0.05). Significant reduction of tissue oxidative stress biomarkers was also observed. Histological analyses confirmed wound healing activity of TG extract, as well. Considering the antioxidative stress and anti-inflammatory activities of TG, explained by the high content of phenolic compounds of the plant, standardized TG extract could be considered as a natural remedy for the treatment of burn wounds. Further clinical studies are suggested to confirm the effectiveness of TG as a wound healing agent. Keywords: Tragopogon graminifolius, Second-degree burn, Oxidative stress, Medicinal plan

Protective effects of curcumin against traumatic brain injury

Neuroinflammation is a key pathophysiological mechanism implicated in the neurodegenerative condition. One  such condition implicating neuroinflammation is traumatic brain injury (TBI). Over the past decades, various  alternative natural compounds, such as curcumin, have been investigated as novel therapeutic options to miti?gate the pathophysiological pathways and clinical sequelae involved in TBI. As the main component of turmeric  (Curcuma longa), curcumin has a broad range of clinical properties due to its considerable antioxidative and anti?inflammatory actions. This review discusses the pleiotropic mechanisms, the side effects, curcumin’s delivery to  the central nervous system (CNS), and its immunomodulatory and protective effects on TBI. Clinical trials, in  vivo, and in vitro studies were extracted from different scientific databases, including PubMed, Scopus, and  Google Scholar, to assess the effects of curcumin or its derivatives in TBI. Findings reveal that curcumin exhibited  some protective effects on TBI via modulation of cell signaling pathways including toll-like receptor-4 (TLR-4),  nuclear factor kappa B (NF-κB), and Nod-like receptor family proteins (NLRPs). Moreover, curcumin upregulates  the brain-derived Neurotrophic Factor/Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway,  phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), nuclear factor erythroid 2-related factor 2 (Nrf2),  which have crucial functions in modulation of TBI pathophysiological-mediated pathways. Curcumin displays  beneficial immunomodulatory functions and protective capacities in different TBI models, although more clinical  experiments are required to clarify curcumin’s precise mechanisms and function in TBI.  </p

Effects of fresh packed red blood cells (RBC) on blood pH, P_CO2, plasma electrolytes and troponin I.

<p>Values are expressed as mean ± S.E.M.</p