• anti-inflammatory effects
• antioxidant properties
• beta-adrenoreceptor antagonists
• carvedilol
• glucose control
• metabolic diseases
• nebivolol
• β-blockers

• Carvedilol
• Depression
• Diabetic peripheral neuropathic pain
• Gut microbiota

• Animals
• Gastrointestinal Microbiome/drug effects
• Carvedilol/pharmacology
• Carvedilol/therapeutic use
• Male
• Antidepressive Agents/pharmacology
• Antidepressive Agents/therapeutic use
• Mice
• Depression/drug therapy
• Depression/microbiology
• Streptozocin
• Diabetic Neuropathies/drug therapy
• Diabetic Neuropathies/microbiology
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Experimental/complications
• Diabetes Mellitus, Experimental/psychology
• Diabetes Mellitus, Experimental/microbiology
• Hyperalgesia/drug therapy
• Mice, Inbred C57BL

• PPAR-γ
• adherens junction
• carvedilol
• mirabegron
• notch
• presenilin
• smad-7
• β-Amyloid

Anxiety disorders are the most prevalent psychiatric disorders being also a comorbid state of other diseases. We aimed to evaluate the anxiolytic-like effects of carvedilol (CVD), a drug used to treat high blood pressure and heart failure with potent antioxidant effects, in animals exposed to chronic unpredictable stress (CUS). To do this, female Swiss mice were exposed to different stressors for 21 days. Between days 15 and 21, the animals received oral CVD (5 or 10 mg/kg) or the antidepressant desvenlafaxine (DVS 10 mg/kg). On the 22^nd day, behavioral tests were conducted to evaluate locomotor activity (open field) and anxiety-like alterations (elevated plus-maze—EPM and hole board—HB tests). After behavioral determinations, the animals were euthanized, and the adrenal gland, blood and brain areas, prefrontal cortex (PFC), and hippocampus were removed for biochemical analysis. CUS reduced the crossings while increased rearing and grooming, an effect reversed by both doses of CVD and DVS. CUS decreased the number of entries and permanence time in the open arms of the EPM, while all treatments reversed this effect. CUS reduced the number of head dips in the HB, an effect reversed by CVD. The CUS reduced weight gain, while only CVD5 reversed this effect. A reduction in the cortical layer size of the adrenal gland was observed in stressed animals, which CVD reversed. Increased myeloperoxidase activity (MPO) and interferon-γ (IFN-γ), as well as reduction of interleukin-4 (IL-4) induced by CUS, were reversed by CVD. DVS and CVD increased IL-6 in both brain areas. In the hippocampus, DVS caused an increase in IFN-γ. Our data show that CVD presents an anxiolytic effect partially associated with immune-inflammatory mechanism regulation.

• COX2
• Carvedilol
• NF-κB
• TNF-α
• iNOS
• intestinal toxicity

• antihypertensive drugs
• cardiology
• cellular response
• humoral response
• immunology
• immunomodulatory effect

• Brain-derived neurotrophic factor
• Carvedilol
• Chronic unpredictable stress
• Depression
• Oxidative stress

• L-glutamine
• gastric emptying
• intestinal inflammation
• physical exercise
• ulcerative colitis

Inflammatory bowel disease (IBD) refers to a group of disorders characterized by chronic inflammation of the gastrointestinal (GI) tract. The elevated levels of nitric oxide (NO) in serum and affected tissues; mainly synthesized by the inducible nitric oxide synthase (iNOS) enzyme; can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation. Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs. Thereby, the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway. Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018. We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factor κB (NF-κB) and JAK/STAT signaling pathways. Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms. A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway (i.e., dexamethasone, pioglitazone, tropisetron) or independent from this pathway (i.e., nicotine, prednisolone, celecoxib, β-adrenoceptor antagonists). Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.

• Inflammatory bowel disease
• Ulcerative colitis
• Crohn’s disease
• Nitric oxide
• Nuclear factor-κB
• Natural or synthetic mediators

• Colitis
• Humans
• Inflammatory Bowel Diseases/drug therapy
• NF-kappa B/metabolism
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Signal Transduction

• Carvedilol
• NF-κB
• inflammation
• oxidative stress
• ulcer

• COX2
• NLRP3 inflammasome
• Oxidative stress
• Simvastatin
• Ulcerative colitis

• Anti-inflammatory
• Antioxidant activity
• Antispasmodic
• Histological study
• Passiflora caerulea
• Ulcerative colitis model

• Animals
• Colitis/drug therapy
• Disease Models, Animal
• Female
• Mice
• Passiflora/chemistry
• Plant Extracts/therapeutic use

Oxidative stress (OS) is considered as one of the etiologic factors involved in several signals and symptoms of inflammatory bowel diseases (IBD) that include diarrhea, toxic megacolon and abdominal pain. This systematic review discusses approaches, challenges and perspectives into the use of nontraditional antioxidant therapy on IBD, including natural and synthetic compounds in both human and animal models. One hundred and thirty four papers were identified, of which only four were evaluated in humans. Some of the challenges identified in this review can shed light on this fact: lack of standardization of OS biomarkers, absence of safety data and clinical trials for the chemicals and biological molecules, as well as the fact that most of the compounds were not repeatedly tested in several situations, including acute and chronic colitis. This review hopes to stimulate researchers to become more involved in this fruitful area, to warrant investigation of novel, alternative and efficacious antioxidant-based therapies.

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Major biomarkers used for evaluation of antioxidant therapy were MPO, TBARS/MDA and glutathione levels.

• Antioxidant therapy
• Biomarkers
• Complementary and alternative medicine
• Crohn's disease
• Inflammatory bowel diseases
• Nutraceuticals
• Oxidative stress
• Ulcerative colitis