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Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazol (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4- chlorophenyl)selanyl)-3, 5-dimethyl-1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4- (phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5-dimethyl1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b), and 3,5- dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, 4-(arylcalcogenyl)-1H-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a, 1b, and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azinobis(3-ethylbenzthiazoline-6- sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a, 1b, and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of [delta]-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a, 1b, and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays. Key words: antioxidant, organoselenium, oxidative stress, toxicity, pyrazoles. Les pyrazoles representent une importante classe de composes heterocycliques dotes de proprietes pharmacologiques. La presente etude portait sur le potentiel antioxydant de composes derives des pyrazoles dans le cerveau de souris in vitro et sur l'effet des composes derives des pyrazoles sur les parametres des dommages et de la toxicite lies a l'oxydation dans le cerveau et le plasma de souris. Les composes evalues etaient les suivants : 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)- 3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4chlorophenyl)selanyl)-3,5-dimethyl- 1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4-(phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5- dimethyl-1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b) et 3,5-dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, les 4- (arylcalcogenyl)1H-pyrazoles, dans des proportions moleculaires faibles, entrainaient une diminution des taux de peroxydation lipidique et de derives reactifs dans des homogenats de cerveaux de souris. Les composes presentaient aussi une capacite de reduction ferrique, ainsi que de piegeage de l'oxyde nitrique. En particulier, les composes 1a, 1b et 1c affichaient une activite de piegeage efficace du 1,1-diphenyl-2-picryl-hydrazyle. Les composes 1b et 1c affichaient une activite de piegeage du 2,20-azino-bis (3-ethylbenzthiazoline-6-acide sulfonique). Les epreuves in vivo ont montre que les composes 1a, 1b et 1c (a 300 mg/kg, avec administration unique par voie intragastrique) n'ont pas entraine de diminution de l'activite de la dehydratase de l'acide [delta]-aminolevulinique, une enzyme qui presente une sensibilite elevee en situation de pro-oxydation, dans le cerveau, le foie et les reins de souris. Le compose 1c entrainait intrinsequement une diminution de la peroxydation lipidique dans le cerveau et le foie de souris. Les epreuves toxicologiques montrent que les composes 1a, 1b et 1c ne presentent pas de toxicite quant a l'aspartate aminotransferase et a l'alanine aminotransferase ainsi qu'aux taux d'uree et de creatinine dans le plasma. En conclusion, les resultats ont montre l'activite antioxydante de composes derives des pyrazoles dans le cadre d'epreuves in vitro. En outre, les resultats ont montre la faible toxicite des composes dans le cadre d'epreuves in vivo. Mots-des : antioxydant, organoselenium, stress oxydatif, toxicite, pyrazoles., Introduction Pyrazole, a five-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions (Fig. 1), is reported to possess a wide range of biological activities [...]

Aims The protective effects of Bacillus amyloliquefaciens (CCT7935), Bacillus subtilis (CCT7935), Bacillus licheniformis (CCT 7836), and Bacillus coagulans (CCT 0199) against lipopolysaccharide (LPS)-induced intestinal inflammation were investigated. Methods and results Male Swiss mice were assigned into six groups: control group, LPS group, LPS +  B. subtilis (CCT7935) group, LPS +    B. licheniformis (CCT 7836) group, LPS +    B. amyloliquefaciens (CCT7935) group, and LPS    + B. coagulans (CCT 0199) group. Each mouse of the groups Bacillus received 1 × 109 colony-forming units of Bacillus once daily by oral gavage during 30 days. Twenty-four hours after the last dose of Bacillus , all groups, except the control group, were intraperitoneally injected with LPS in the single dose of 15 mg kg−1. The mice were euthanized 24 h after the LPS administration. Histological alterations, myeloperoxidase activity, and nitrite levels were analyzed in the gut of mice and the inflammatory cytokines were analyzed in the gut and in the blood. The results demonstrate that the mice challenged with LPS presented the villi shortened and damaged, which were significantly protected by B. coagulans and B. amyloliquefaciens. Furthermore, all Bacillus tested were effective in preventing against the increase of myeloperoxidase activity, while B. amyloliquefaciens and B. subtilis prevented the increase of nitrite and IL-1β levels in the gut of mice induced with LPS was decreased only B. subtilis. LPS also elevated the IL-1 β, IL-6, and IL-10 levels in the blood, and these alterations were significantly suppressed by Bacillus , especially by B. subtilis. Conclusions The study suggests that the Bacillus investigated in this study might be effective therapeutic agents for preventing intestinal inflammation, because they decrease the inflammatory process an protect against tissue damage. [ABSTRACT FROM AUTHOR]

We describe herein the synthesis, molecular docking, protein–ligand interactions and biological validation of 1,2,3-triazolyl-carboxamides containing sulfonamide moieties as anti-inflammatory agents through the inhibition of myeloid hemoprotein myeloperoxidase (MPO) activity. The named compounds were synthesized in good yields under mild conditions, by a [3+2]-cycloaddition reaction of sulfamoyl-β-oxo-amides and aryl azides in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Given the higher affinity of some of the synthesized compounds with MPO, their inhibitory activity was evaluated on the plasma of mice as previously reported with a lipopolysaccharide. The obtained results suggest that the sulfamoyl-1,2,3-triazolyl-carboxamides are interesting and promising candidates for further studies on their anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

Many studies have suggested that imbalance of the gut microbial composition leads to an increase in pro-inflammatory cytokines and promotes oxidative stress, and this are directly associated with neuropsychiatric disorders, including major depressive disorder (MDD). Clinical data indicated that the probiotics have positive impacts on the central nervous system and thus may have a key role to treatment of MDD. This study examined the benefits of administration of Komagataella pastoris KM71H (8 log UFC·g–1/animal, intragastric route) in attenuating behavioral, neurochemical, and neuroendocrine changes in animal models of depressive-like behavior induced by repeated restraint stress and lipopolysaccharide (0.83 mg/kg). We demonstrated that pretreatment of mice with this yeast prevented depression-like behavior induced by stress and an inflammatory challenge in mice. We believe that this effect is due to modulation of the permeability of the blood-brain barrier, restoration in the mRNA levels of the Nuclear factor kappa B , Interleukin 1β , Interferon γ , and Indoleamine 2 3-dioxygenase , and prevention of oxidative stress in the prefrontal cortices, hippocampi, and intestine of mice and of the decrease the plasma corticosterone levels. Thus, we conclude that K. pastoris KM71H has properties for a new proposal of probiotic with antidepressant-like effect, arising as a promising therapeutic strategy for MDD. [Display omitted] • K. pastoris KM71H attenuated depression-like behavior in mice. • K. pastoris KM71H mitigated oxidative stress. • K. pastoris KM71H decreased the corticosterone levels. • K. pastoris KM71H restored the mRNA levels of the NFκB , IL-1β , INF γ , and IDO. [ABSTRACT FROM AUTHOR]