Synthesis, and evaluation of α-amylase and α-glucosidase inhibitory potential of new pyrazolo[3,4-d]pyrimidine derivatives

A series of new pyrazolo[3,4-d]pyrimidine compounds were synthesized in excellent yields via sulfuration and 1,3-dipolar cycloaddition and confirmed by MS, FT-IR and NMR techniques. All the prepared compounds were screened in vitro for their α-amylase and α-glucosidase inhibitory activities. Preliminary results indicated that some target compounds exhibited promising α-amylase and α-glucosidase inhibitory activity potency. Among the tested products, the cycloadduct f was found most active inhibitor (IC50 = 134.30 μM) for α-amylase, and the sulphur product b is the most active inhibitor (IC50 = 16.37 μM) for α-glucosidase

Chemical analysis and anti-oxidation activities of the Moroccan Milk Thistle

The milk thistle (Silybum marianum) seeds Oil and ethanolic extracts were subjected to chemical analysis, and evaluated for their antioxidant activities. Chemical analysis of the Oil was performed by GC-MS. The main fatty acids were linoleic (48.26%), oleic (27.71%) and palmitic (7.67%) acids. While sterols major element was ß-sitosterol (27.06%) followed by cholesterol (22.38%). Antioxidant activity was examined using DPPH (353.89 ± 3.68) and ABTS (805.25 ± 16.90) mg TE/ g edw; also FRAP (8.38 ± 0.12 AAE/g edw) assays. Phenolic and flavonoid contents were much more higher in ethanolic extract (45.31 ± 1.75 mg GAE/g edw - 33.23 ± 0.87 mg RE/g edw). In summary, chemometric comparisons with our previous analysis of lipids from Moroccan Oils demonstrated the interesting and unique profile of the milk thistle Oil for nutritional diet and therapies

Phytochemical screening and in vitro evaluation of alpha amylase, alpha glucosidase and beta galactosidase inhibition by aqueous and organic Atractylis gummifera L. extracts

Diabetes is a chronic condition which is increasingly progressing throughout the world. To treat it, several methods are used, among which is medicinal plants that still have an unknown mechanism of action. The objective of this work is to evaluate the in vitro hypoglycemic effect of the extracts of the underground part of Atractylis gummifera, a member of Asteraceae used in traditional Moroccan medicine. A phytochemical study of the aqueous extracts (decocted, infused and macerated) and organic extracts (methanol, methanol macerate, chloroformic, ethyl acetate and petroleum ether), and a phytochemical screening of the different secondary metabolites was done. The antidiabetic power of the extracts of A. gummifera by testing the inhibitory activity of ?-amylase, ?-glucosidase and ?-galactosidase, which are enzymes responsible for the digestion of polysaccharides was determined. The extracts of A. gummifera are very rich in flavonoids and tannins, and are inhibitory to?-amylase and ?-glucosidase, mainly the macerate of methanol with IC50 values of 0.557 ± 0.013 and 0.743 ± 0.017 mg / mL respectively. Higher ?-galactosidase inhibitory potential than quercetin was observed for aqueous macerates and methanol with IC50 values of 2.23 ± 0.012 and 2.443 ± 0.071 mg / mL respectively. The extracts of A. gummifera possess a significant inhibitory activity of the alpha amylase and alpha glucosidase and beta-galactosidase enzymes, in particular the macerate of methanol followed by the aqueous macerate, among the eight extracts tested

Origin and Evolution of TRIM Proteins: New Insights from the Complete TRIM Repertoire of Zebrafish and Pufferfish

Tripartite motif proteins (TRIM) constitute a large family of proteins containing a RING-Bbox-Coiled Coil motif followed by different C-terminal domains. Involved in ubiquitination, TRIM proteins participate in many cellular processes including antiviral immunity. The TRIM family is ancient and has been greatly diversified in vertebrates and especially in fish. We analyzed the complete sets of trim genes of the large zebrafish genome and of the compact pufferfish genome. Both contain three large multigene subsets - adding the hsl5/trim35-like genes (hltr) to the ftr and the btr that we previously described - all containing a B30.2 domain that evolved under positive selection. These subsets are conserved among teleosts. By contrast, most human trim genes of the other classes have only one or two orthologues in fish. Loss or gain of C-terminal exons generated proteins with different domain organizations; either by the deletion of the ancestral domain or, remarkably, by the acquisition of a new C-terminal domain. Our survey of fish trim genes in fish identifies subsets with different evolutionary dynamics. trims encoding RBCC-B30.2 proteins show the same evolutionary trends in fish and tetrapods: they evolve fast, often under positive selection, and they duplicate to create multigenic families. We could identify new combinations of domains, which epitomize how new trim classes appear by domain insertion or exon shuffling. Notably, we found that a cyclophilin-A domain replaces the B30.2 domain of a zebrafish fintrim gene, as reported in the macaque and owl monkey antiretroviral TRIM5α. Finally, trim genes encoding RBCC-B30.2 proteins are preferentially located in the vicinity of MHC or MHC gene paralogues, which suggests that such trim genes may have been part of the ancestral MHC

Antioxidant Activity and Inhibitory Potential of Cistus salviifolius (L.) and Cistus monspeliensis (L.) Aerial Parts Extracts against Key Enzymes Linked to Hyperglycemia

Cistus genus (Cistaceae) comprises several medicinal plants used in traditional medicines to treat several pathological conditions including hyperglycemia. These include Cistus salviifolius L. (CS) and Cistus monspeliensis L. (CM), still not fully explored as a source of metabolites with therapeutic potential for human diseases. In this study, the antioxidant α-amylase and α-glucosidase enzyme inhibitory effects of aqueous and hydromethanolic extracts from the aerial parts of Moroccan CS and CM were investigated. Antioxidant activity has been assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals and ferric reducing/antioxidant power (FRAP) methods. The α-amylase and α-glucosidase inhibitory activity has been assessed using an in vitro model. Moreover, mineral and phenolic contents of CS and CM were analyzed. The extracts of both species exhibited potent antioxidant activity in all used systems and possess strong inhibitory effect towards α-glucosidase (IC50: 0.95±0.14 to 14.58±1.26 μg/mL) and significant inhibitory potential against α-amylase (IC50: 217.10±0.15 to 886.10±0.10 μg/mL). Furthermore, the result showed high levels of phenolic content and unexpectedly some higher levels of mineral content in CS. The results suggest that the phenolic rich extracts of CS and CM may have a therapeutic potential against diseases associated with oxidative stress and may be useful in the management of hyperglycemia in diabetic patients

Comparative Study of Leaf and Rootstock Aqueous Extracts of Foeniculum vulgare on Chemical Profile and In Vitro Antioxidant and Antihyperglycemic Activities

Foeniculum vulgare is a medicinal plant used in Moroccan folk medicine to treat several diseases such as diabetes. The aim of this study was to determine the phenolic bioactive compounds and to evaluate the antioxidant and antihyperglycemic activities of Foeniculum vulgare leaf and rootstock extracts. Phenolic compounds of F. vulgare rootstock and leaf extracts were determined using HPLC-DAD-QTOFMS analysis. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) radicals. Moreover, the in vitro antihyperglycemic effects were tested by measuring the inhibition of α-amylase and α-glucosidase activities. HPLC-DAD-QTOFMS analysis identified thirty-two phenolic components in both leaf and rootstock extracts. Caffeic acid, quinic acid, and chlorogenic acid were the major compounds of F. vulgare leaf extract (FVLE), while the main compound of F. vulgare rootstock extracts (FVRE) was quinic acid. In the DPPH assay, F. vulgare leaf extract showed important antioxidant activity (IC50 = 12.16 ± 0.02 μg/mL) than F. vulgare rootstock extract (IC50 = 34.36 ± 0.09 μg/mL). Moreover, fennel leaf extracts revealed also the most powerful antioxidant activity (IC50 = 22.95 ± 0.4 μg/mL) in the ABTS assay. The in vitro antihyperglycemic activity showed that F. vulgare rootstock extract exhibited a remarkable inhibitory capacity (IC50 = 194.30 ± 4.8 μg/mL) of α-amylase compared with F. vulgare leaf extract (IC50 = 1026.50 ± 6.5 μg/mL). Furthermore, the inhibition of α-glucosidase was more importantly with F. vulgare rootstock (IC50 of 165.90 ± 1.2 μg/mL) than F. vulgare leaf extracts (203.80 ± 1.3 μg/mL). The funding of this study showed that F. vulgare rootstock and leaf extracts presented several phenolic compounds and showed important antioxidant and antidiabetic effects. We suggest that the identified molecules are responsible for the obtained activities. However, further studies focusing on the isolation and the determination of antioxidant and antidiabetic effects of F. vulgare rootstock and leaf main compounds are required

Evaluation of In Vitro Antioxidant and Antidiabetic Activities of Aristolochia longa Extracts

Oxidative stress plays a major role in diabetic physiopathology; hence, the interest of using natural antioxidants as therapeutic tools exists. The aim of this study was the evaluation of in vitro antioxidant activity and inhibitory potential of organic extracts from Aristolochia longa roots against key enzymes linked to hyperglycemia. Antioxidant activity was performed using 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals and ferric reducing/antioxidant power (FRAP) methods. The α-Glucosidase and β-Galactosidase inhibitory activities were investigated using an in vitro model. Moreover, phytochemical analysis of tested extracts was carried out. The aqueous fraction of this herb exhibited the highest antioxidant activity for both DPPH and ABTS methods, IC50=125.40±2.40 μg/mL and IC50=65.23±2.49 μg/mL, respectively. However, the ethyl acetate fraction possessed the strongest inhibitory effect towards α-Glucosidase (IC50=1.112±0.026 mg/mL). Furthermore, the result showed high levels of phenolic content. The results showed that this plant could be a significant source of medically important natural compounds

Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation

The impact of allograft injury time of onset on the risk of chronic lung allograft dysfunction (CLAD) remains unknown. We hypothesized that episodes of late-onset (≥6 months) allograft injury would produce an augmented CXCR3/ligand immune response, leading to increased CLAD. In a retrospective single-center study, 1894 transbronchial biopsy samples from 441 lung transplant recipients were reviewed for the presence of acute rejection (AR), lymphocytic bronchiolitis (LB), diffuse alveolar damage (DAD), and organizing pneumonia (OP). The association between the time of onset of each injury pattern and CLAD was assessed by using multivariable Cox models with time-dependent covariates. Bronchoalveolar lavage (BAL) CXCR3 ligand concentrations were compared between early- and late-onset injury patterns using linear mixed-effects models. Late-onset DAD and OP were strongly associated with CLAD: adjusted hazard ratio 2.8 (95% confidence interval 1.5-5.3) and 2.0 (1.1-3.4), respectively. The early-onset form of these injury patterns did not increase CLAD risk. Late-onset LB and acute rejection (AR) predicted CLAD in univariable models but lost significance after multivariable adjustment for late DAD and OP. AR was the only early-onset injury pattern associated with CLAD development. Elevated BAL CXCR3 ligand concentrations during late-onset allograft injury parallel the increase in CLAD risk and support our hypothesis that late allograft injuries result in a more profound CXCR3/ligand immune response

The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome

Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF-β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single-center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF-β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF-β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76-5.38) for the most severe form of PGD. TGF-β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF-β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF-β biology