Evaluation of anti-inflammatory and antioxidant activities of Sedum sediforme extracts

Purpose: To evaluate the in vivo anti-inflammatory effect and in vitro antioxidant activity of the areal part of Sedum sediforme (Jacq.) extracts.Methods: The plant was extracted with solvents of varying polarity (Methanol, chloroform and ethyl acetate, respectively) allowed its separation into three sub-fractions: crude extract, chloroform extract and ethyl acetate extract (CrE, ChE and EaE, respectively). Total polyphenol contents of the extracts were determined. The phorbolmyristate acetate (PMA) induced mice ear edema method was using to evaluate the anti-inflammatory activity. The in vitro scavenging activity was evaluated using enzymatic and non-enzymatic methods. Chelating ability of extracts was assessed using Fe2+–ferrozine complex.Results: The highest content of phenolics compound was in EaE. The administration of CrE (12.5 and 25 mg/kg) reduced ear edema induced by PMA (%I = 35.81 ± 3.18 % and 38.57 ± 2.80 %, respectively), the effect was comparable with that of diclofenac used as a reference drug (%I = 38.84 ± 1.87 %). The in vitro scavenging activity of S. sediforme extracts confirmed that the CrE has the highest enzymatic and non-enzymatic activity with a half maximal inhibitory concentration (IC50) = 0.063 ± 0.005 mg/mL and 0.178 ± 0.006 mg/mL, respectively. However, the ChE present an excellent  chelating activity with a half-maximal effective concentration (EC50) of 0.397 ± 0.001 mg/mL.Conclusion: The results show that S. sediforme extracts have a strong antioxidant and antiinflammatory activities which lend some support their use in the traditional medicine. Keywords: Sedum sediforme, Anti-inflammatory, Superoxide scavenger, Cytochrome C, Metal chelatin

INHIBITORY EFFECTS OF ANCHUSA AZUREA EXTRACTS ON XANTHINE OXIDASE ACTIVITY AND ITS HYPOURICEMIC EFFECTS ON MICE

Objective: The aim of the present study was to determine the effects of the polyphenols and flavonoids from Anchusa azurea on XO activities in vitro and on serum and liver uric acid levels in normal and potassium oxonate-induced hyper uricemic mice. In addition, the renal function of the mice after flavonoid administration was estimated by the determination of blood urea and creatinine analysis.Methods: In the present study, Anchusa azurea were extracted with solvent of varying polarity allowed its separation into four subfractions: crude extract (Cr) chloroform extract (ChE), ethyl acetate extract (AcE), and aqueous extracts (AqE). Total polyphenol and flavonoids contents of Anchusa azurea extracts were determined. The inhibitory activity of the extracts on the XO was evaluated and the type of inhibition was determined. Hyperuricemia is induced by intraperitoneally injection of potassium oxonate, the uric acid, urea and creatinine were measured in serum and supernatant of the liver. The effect of the extracts on renal function was evaluated. The rate of urea and creatinine levels can be indicators for the assessment of renal function.Results: AcE were the richest in polyphenols and ChE was the richest fraction in flavonoids. The inhibitory activity of the extracts on the XO was evaluated, the results obtained showed that the inhibition is dose-dependent and ChE and AcE have the best inhibitory effect (IC50= 0.334±0.006 and 0.263±0.002 mg/ml, respectively), and both showed a noncompetitive type of inhibition. For antihyperuricemic effect, AqE and CrE caused a decrease in serum uric acid (a decrease of 66%) followed by ChE with a percentage of 29.22 %. The AcE keeps almost the same value of uric acid of "PO" group. For the supernatant, only CrE caused a significant decrease of liver uric acid (18.5±4.83 mg/l). This decrease can be explained by the significant inhibition of the XO by inhibition of the synthesis pathways of uric acid. Comparing the urea level of "OP" group (0.48 g/l), only extracts CrE-AA, AqE-AA (0.41g/l, 0.39 g/l) decreased the level of urea significantly (P ≤ 0.05) to the normal values of urea (0.34 g/l), we can conclude that the rate of urea and creatinine after treatment with plant extracts are normal and that the results of this study indicate the absence of renal damage in miceConclusion: Anchusa azurea fractions have a strong inhibitory effect on xanthine oxidase and also have a significant lowering effect on serum and liver creatinine and urea levels in hyper uricemic mice.Â

Negative symptoms and sex differences in first episode schizophrenia: What's their role in the functional outcome? A longitudinal study

Introduction: Negative symptoms (NS) include asociality, avolition, anhedonia, alogia, and blunted affect and are linked to poor prognosis. It has been suggested that they reflect two different factors: diminished expression (EXP) (blunted affect and alogia) and amotivation/pleasure (MAP) (anhedonia, avolition, asociality). The aim of this article was to examine potential sex differences among first-episode schizophrenia (FES) patients and analyze sex-related predictors of two NS symptoms factors (EXP and MAP) and functional outcome. Material and methods: Two hundred and twenty-three FES (71 females and 152 males) were included and evaluated at baseline, six-months and one-year. Repeated measures ANOVA was used to examine the effects of time and sex on NS and a multiple linear regression backward elimination was performed to predict NS factors (MAP-EXP) and functioning. Results: Females showed fewer NS (p = 0.031; Cohen's d = −0.312), especially those related to EXP (p = 0.024; Cohen's d = −0.326) rather than MAP (p = 0.086), than males. In both male and female group, worse premorbid adjustment and higher depressive symptoms made a significant contribution to the presence of higher deficits in EXP at one-year follow-up, while positive and depressive symptoms predicted alterations in MAP. Finally, in females, lower deficits in MAP and better premorbid adjustment predicted better functioning at one-year follow-up (R2 = 0.494; p < 0.001), while only higher deficits in MAP predicted worse functioning in males (R2 = 0.088; p = 0.012). Conclusions: Slightly sex differences have been found in this study. Our results lead us to consider that early interventions of NS, especially those focusing on motivation and pleasure symptoms, could improve functional outcomes

A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood

Little is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse. © 2021, The Author(s)

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages

PROPRIETES ANTIOXYDANTES ET ACTIVITE INHIBITRICE DE LA XANTHINE OXYDASE DES EXTRAITS DE LA PLANTE MEDICINALE PEGANUM HARMALA L.

Dans le presente travail, l.activite antioxydante des differents extraits prepares a partir des graines de Peganum harmala et leur effet inhibiteur vis-a-vis la XO ont evalue. La XO a ete purifiee du lait bovin, le PFR est de 5.15, et avec une bande majeure d.environ 150 KDa, en SDS-PAGE, et une activite specifique de 2055.05 nmol / min / mg proteine. L.analyse des extraits methanolique (EBr), chloroformique (ECh) et acetate d.ethyle (EAc) a montre que l.ECh represente la fraction la plus riche en polyphenols et flavonoides (66.29 ¡¾ 1.57 mg EAG / g d.extrait sec et 13.88 ¡¾ 0.13 mg EQ / g d'extrait sec), respectivement, suivi par l.EAc (58.1 ¡¾ 1.57 mg EAG / g d.extrait sec et 12.18 ¡¾ 0.08 mg EQ / g d'extrait sec), et enfin l.EBr, avec la plus faible teneur (27.91 ¡¾ 0.98 mg EAG / g d'extrait sec et 7.39 ¡¾ 0.68 mg EQ / g d'extrait sec). L.ECh presente l'inhibion la plus puissante de la XO (IC50 = 0.055 ¡¾ 0.0053 mg / ml) et la reduction du Cyt c (IC50 = 0.037 ¡¾ 0.0008 mg / ml), suivi par l.EAc avec des IC50 de 0.0057¡¾0,0141 et 0.053 ¡¾ 0.0141 mg / ml, respectivement. Enfin, l.EBr possede un faible effet (IC50 = 0.252 ¡¾ 0.0051 mg / ml et 0.14 ¡¾ 0.0051 mg / ml, respectivement). L.EBr possede l.effet scavenger sur le radical DPPH le plus eleve (IC50 = 0,100 ¡¾ 0.0069 mg / ml), suivi par l.EAc et l.ECh avec des IC50 de 0,711 ¡¾ 0,0298 et 0,744 ¡¾ 0,0198 mg / ml, respectivement. Dans le test de ¥â-carotene / acide linoleique, les extraits des graines ont une activite antioxydante tres importante. Les resultats ont montre que l.activite antioxydante la plus elevee etait celle de l.EAc (94.21 ¡¾ 0.003 %), suivi par l.EBr et l.ECh avec 86.24 ¡¾ 0.027% et 77.35 ¡¾ 0.032 %, respectivement. Le test de la capacite chelatrice des ions ferreux a montre que les extraits EBr, EAc et ECh sont de bons chelateurs avec des IC50 de 0.088 ¡¾ 0.0008, 2.256 ¡¾ 0.0398 et 5.286 ¡¾ 0.0053 mg/ml, respectivement. Les resultats obtenus suggerent que ces produits naturels peuvent etre utilises pour traiter les maladies qui necessitent l.inhibition de la XO, le piegeage des radicaux libres et / ou l.inhibition de la peroxydation lipidique

The In vivo and in vitro antioxidant and anti-hemolytic effect of Algerian Centaurea calcitrapa L. extracts

In the present study, aerial part of Centaurea calcitrapa L. were extracted with solvent of varying polarity allowed their separation into three main subfractions, the analysis of methanol crud (CrE), chloroform (ChE) and ethyl acetate (EaE) extracts, showed that the EaE contains the highest amount of flavonoids (50,71 ± 0,65 mg Eq / Quercetin g dry extract and 31,96 ± 0,39 mg Eq Rutin / g dry extract). Using DPPH assay, the highest activity was observed with EaE (IC50 = 0,037 ± 0,0006 mg / ml). The β-carotene / linoleic acid bleaching assay revealed that the extracts have a very important antioxidant activity. The results showed that CrE has the highest antioxidant activity. The antioxidant activity of the CrE is confirmed by an in vivo assay in mice, using two doses: CrD1 (50 mg/kg/day) and CrD2 (100 mg/kg/day) during 21 days. Total antioxidant capacity of plasma and red blood cells was measured. The half-life (HT50), which corresponds to 50% of cell lysis was calculated, the results showed that both groups treated with plant extract had a protective effect against erythrocytes hemolysis (CrD2: HT50= 167,3 ± 3,72 min). The CrD2 group showed a strong scavenging activity using DPPH assay (51,64 ± 5,24 %), higher than that of Vit C group (38,92 ± 1,72 %). All results confirmed that the extracts have a dose dependent effect on the growth of overall antioxidant defenses. These results support the use of this plant against anti-inflammatory diseases in traditional medicine. Keywords: Centaurea calcitrapa L., in vivo-antioxidant activity, DPPH, hemolysis, flavonoids

Phenolics Contents, Xanthine Oxidoreductase Inhibitory Potential, Antibacterial and Antioxidant Activities of Cachrys libanotis L. Root Extracts

To date, no studies have investigated the phytochemical screening and biological activities of Cachrys libanotis L. traditionally used for the treatment of gout and rheumatism. Therefore, we aimed to investigate, for the first time, the phytochemical contents, the xanthine oxidoreductase inhibition, antibacterial, and antioxidant activities of extracts derived from the roots of C. libanotis L. Roots were submitted to extraction and fractionation using three different solvents sequentially, in the ascending order of polarity. Subsequently, XOR was purified from bovine milk and its inhibition was evaluated using xanthine/XOR system. The antioxidant activities were assessed employed superoxide scavenging, β- carotene bleaching, DPPH scavenging, ferrous iron chelation and FRAP assays). The antibacterial activity was tested by disc diffusion assay against 11 ATCC strains. Extraction and fractionation gave crude extract (CrE), hexane extract (HxE), chloroform extract (ChE), ethyle acetate extract (EAE) and aqueous extract (AqE).&nbsp; EAE exhibited the highest XOR inhibitory effect. CrE exhibited the highest effect as DPPH scavenger. All fractions exhibited a good activity against linoleate oxidation. Both CrE and AqE had an excellent chelating activity. Extracts showed a medium reducing power with greatest value exhibited by EAE. The plant extracts exhibited moderate to good antibacterial activity where the HxE extract had the strongest antimicrobial activity. From the obtained results, C. libanotis roots might be helpful in preventing or slowing the progress of gout, and it could be used as an additive in the food industry providing good protection against oxidative damage. Keywords: Cachrys libanotis, polyphenols, oxidative stress, xanthine-oxidoreductase (XOR), antimicrobial

Kinetics of Inhibition of Xanthine Oxidase by Lycium arabicum and its Protective Effect against Oxonate- Induced Hyperuricemia and Renal Dysfunction in Mice

Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects.Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight.Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract.Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.Keywords: Lycium arabicum, Uric acid, Creatinine, Superoxide, Phenolic compounds, Flavonoids, Hyperuricemi