My El Abbes Faouzi

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.

Bioactive metabolites from Chaetomium aureum: Structure elucidation and inhibition of the Hsp90 machine chaperoning activity

Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h.

Phytochemical and pharmacological variability in Golden Thistle functional parts: comparative study of roots, stems, leaves and flowers

Abstract Scolymus hispanicus or the Golden Thistle, locally known as ‘Guernina’ or ‘Taghediwt’, is one of the most appreciated wild vegetables in Morocco. This study aims to characterise the functional chemical and pharmacological variability of Scolymus hispanicus parts (roots, stems, leaves and flowers). The chemical analysis revealed higher content of α-tocopherol in the flowers (2.79 ± 0.07 mg/100 g) and lead to the identification of 3 flavonoids and 13 phenolic acids, with high content of gallic acid in leaves (187.01 ± 10.19 mg/kg); chlorogenic (936.18 ± 92.66 mg/kg) and caffeic (4400.14 ± 191.43 mg/kg) acids in flowers, roots were much more higher in sinapic acid (0.25 ± 0.03 mg/kg) compared to the other parts. Moreover, Scolymus hispanicus ethanolic extracts exhibited interesting antioxidant and antimicrobial properties, promising anti-amylase and anti-glucosidase activities and relevant diuretic effect that confirms its traditional uses.

Cholesterol lowering effect in the gall bladder of dogs by a standardized infusion of Herniaria hirsuta L.

ETNOPHARMACOLOGICAL RELEVANCE Infusions of Herniaria hirsuta L., Herniaria glabra L. and Herniaria fontanesii J.Gay are well known in Moroccon folk medicine for the treatment of biliary dyskinesia, (uro)lithiasis or as a diuretic. Herniariae Herba which can contain H. glabra and H. hirsuta is known in Europe as an urological drug. AIM OF THE STUDY To investigate the efficacy of a standardized infusion of Herniaria hirsuta against choleltihiasis, and evaluation of its genotoxicity. METHODS AND MATERIALS An analytical HPLC-UV method to quantify flavonoids and saponins present in the extract of H. hirsuta was developed and validated. An in vivo experiment to evaluate the cholesterol lowering effect of a infusion of H. hirsuta in the gall bladder of dogs was carried out. Dogs were divided into 3 groups i.e. control dogs (CG), dogs treated with ursodeoxycholic acid (UDCA) (2×7.35mg/kg body weight/day) and dogs treated with the standardized infusion (HG) (2×48.5mg/kg body weight/day). Dogs were fed a fatty diet during 120 days after which a diet without additional fat was introduced till day 180. Treatment started 30 days after introduction of the fatty diet and lasted till the end of the experiment. A bile and blood sample of each dog was collected every 30 days, after which the concentration of cholesterol was determined. An Ames test was performed according to the OECD-guidelines. RESULTS The validated HPLC-UV method showed a linear calibration model and an acceptable precision for the total flavonoid content (total content 4.51%) as well as the total saponin content (12.74%). The in vivo experiments already showed a minor difference for bile cholesterol between CG and HG after 30 days of treatment with the infusion, and the difference was more pronounced after 90 days of treatment. Even 30 days after discontinuation of the cholesterol-rich diet a significant difference remained between CG and HG. There was no statistically significant difference in blood cholesterol. The Ames test showed that the infusion of H. hirsuta could be considered as being free from genotoxic risks. CONCLUSION A method for the standardization of a infusion of Herniaria hirsuta was developed and validated. Prolonged use of this standardized H. hirsuta extract resulted in a cholesterol-lowering effect in the bile of dogs. Since this pharmacological effect prevents the formation of gallstones and can contribute to solving existing gallstones, a standardized infusion of H. hirsuta may have a positive effect in the treatment of gallstones in human patients.

Antidiabetic and protective effects of the aqueous extract of Arbutus unedo L. in streptozotocin-nicotinamide-induced diabetic mice

Abstract Background Diabetes mellitus (DM) is currently a major health problem and the most common chronic disease worldwide. Traditional medicinal plants remedies remain a potential adjunct therapy to maintain better glycemic control while also imparting few side-effects. Arbutus unedo L. has been traditionally used to manage several diseases including diabetes. This study was undertaken to contribute the validation of the traditional use of Arbutus unedoL. (Ericaceae) in the treatment of diabetes. Methods In-vitro antidiabetic effect of the A. unedo roots aqueous extract was conducted using α-glucosidase and α-amylase assays. While in-vivo antidiabetic activity was conducted using streptozotocin-nicotinamide (STZ-NA) induced diabetic mice. Diabetic animals were orally administered the aqueous extract in 500 mg/kg of body weight to assess the antidiabetic effect. The blood glucose level and body weight of the experimental animals were monitored for 4 weeks. In addition, the histopathological examination of the treated mice pancreas was also conducted to observe the changes of β-cells during the treatment process. Results The extract produced a significant decrease in blood glucose level in diabetic mice. This decrease was equivalent to that which observed in mice treated with a standard after 2–4 weeks. In addition, the plant extract exhibited a potent inhibitory effect on α-amylase and α-glucosidase activity with IC50 values of 730.15±0.25 μg/mL and 94.81±5.99 μg/mL, respectively. Moreover, the histopathologic examination of the pancreas showed a restoration of normal pancreatic islet cell architecture which observed in the diabetic mice treated with plant extract. Conclusions The aqueous A. unedo roots extract has a significant in vitro and in vivo antidiabetic effects and improves metabolic alterations. The revealed results justify its traditional medicinal use.

In Vitro and In Vivo Antioxidant and Anti-Hyperglycemic Activities of Moroccan Oat Cultivars

Improvement of oat lines via introgression is an important process for food biochemical functionality. This work aims to evaluate the protective effect of phenolic compounds from hybrid Oat line (F11-5) and its parent (Amlal) on hyperglycemia-induced oxidative stress and to establish the possible mechanisms of antidiabetic activity by digestive enzyme inhibition. Eight phenolic acids were quantified in our samples including ferulic, p-hydroxybenzoic, caffeic, salicylic, syringic, sinapic, p-coumaric and chlorogenic acids. The Oat extract (2000 mg/kg) ameliorated the glucose tolerance, decreased Fasting Blood Glucose (FBG) and oxidative stress markers, including Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Glutathione (GSH) and Malondialdehyde (MDA) in rat liver and kidney. Furthermore, Metformin and Oat intake prevented anxiety, hypercholesterolemia and atherosclerosis in diabetic rats. In vivo anti-hyperglycemic effect of Oat extracts has been confirmed by their inhibitory activities on α-amylase (723.91 μg/mL and 1027.14 μg/mL) and α-glucosidase (1548.12 μg/mL & 1803.52 μg/mL) enzymes by mean of a mixed inhibition.

Comparative plasma disposition kinetics of albendazole and its new benzimidazol prodrug in dog.

The comparative pharmacokinetic behavior of albendazole (ABZ) and its new benzimidazol prodrug [1-tert-butyloxycarbonyl-5-propylthio-1-H-benzimidazol-2ylcarbamate of methyl] (ABZBoc), following their oral administration (10mg/kg) to healthy dogs was explored. Blood samples were obtained serially over a 24h period after treatment, then the plasma was analyzed by high-performance liquid chromatography (HPLC) to search the albendazole metabolites (ABZSO and ABZSO2). However, the albendazole parent drug was not detectable at any time after both treatments (ABZ and ABZBoc). By albendazole metabolites (ABZSO and ABZSO2) were the analytes recovered in the plasma after oral administration of ABZ and ABZBoc. Furthermore, some amounts of ABZBoc were also available in the plasma samples treated with this new produg. The plasma profile of each analyte followed a similar pattern after both treatments, the active metabolite (ABZSO) was the major analyte recovered in plasma (between 1 and 24h post-treatment). The pharmacokinetic parameters of both groups were calculated (Cmax, Tmax, t1/2, AUC0-›∞), and analyzed using the Students t-test, P<0.05. Thus,the pharmacokinetic analysis indicated four statistically significant changes in the pharmacokinetic parameters defined above of the albendazole metabolites (ABZSO, ABZSO2) between the group treated with albendazole (group A) and that treated with ABZBoc prodrug (group B). Hence, the levels of the various pharmacokinetics parameters were low in the group treated with prodrug, as well they did not reach equivalent concentrations to that of albendazole. These differences between albendazole and its new prodrug may be explained by the fact that ABZBoc prodrug was not effectively reduced in the intestine of dogs.

Étude comparative de l’estimation in vitro de la fixation plasmatique du 99mTc-DTPA utilisé en scintigraphie rénale

The radiopharmaceutical (99m)Tc-DTPA (diethylene-triamine-pentaacetic acid) is a tracer widely used in renal scintigraphy to assess glomerular filtration rate. The estimation of protein binding is very important due to its impact on clinical parameters biodistribution since only the free fraction is filtered by the kidney. A number of laboratory techniques have been developed to study protein binding. Precipitation and ultrafiltration are the mostly used techniques in pharmacology for studies of the binding between proteins and small molecules. The aim of this work is to apply and compare those two analytical methods in (99m)Tc-DTPA protein binding determination in vitro before in vivo application. The results obtained by precipitation with trichloroacetic acid are not enough reproducible, while those obtained by ultrafiltration seem more consistent and reproducible.

Separation, Identification, and Antidiabetic Activity of Catechin Isolated from Arbutus unedo L. Plant Roots

Phytopharmaceuticals play an essential role in medicine, since the need to investigate highly effective and safe drugs for the treatment of diabetes mellitus disease remains a significant challenge for modern medicine. Arbutus unedo L. root has various therapeutic properties, and has been used widely in the traditional medicine as an antidiabetic agent. The current study aimed to isolate the pharmacologically active compound from A. unedo roots using accelerated solvent extraction technology, to determine its chemical structure using different instrumental analytical methods, and also to evaluate the α-glucosidase inhibitory activity. The roots of A. unedo were exhaustively extracted by high-pressure static extraction using the Zippertex® technology (Dionex-ASE, Paris, France), and the extract was mixed with XAD-16 resin to reach quantifiable amounts of active compounds which were identified by high-pressure liquid chromatography (HPLC), 1H NMR (300 MHz), and 13C NMR. The antidiabetic activity of the isolated compound was evaluated using the α-glucosidase inhibitory assay. The active compound was isolated, and its structure was identified as catechin using instrumental analysis.The results revealed that the isolated compound has potential α-glucosidase inhibitory activity with an IC50 value of 87.55 ± 2.23 μg/mL greater than acarbose. This was used as a positive control, which has an IC50 value of 199.53 ± 1.12 μg/mL. According to the results achieved, the roots of A. unedo were considered the best source of catechin and the Zippertex® technology method of extraction is the best method for isolation of this therapeutic active compound. In addition, the α-glucosidase inhibitory activity results confirmed the traditional use of A. unedo roots as an antidiabetic agent. Future clinical trials and investigations of antidiabetic and other pharmacological effects such as anticancer are required.

Modulatory effect of Syzygium aromaticum and Pelargonium graveolens on oxidative and sodium nitroprusside stress and inflammation

Therapy combination is known for less side effects and higher efficacy. Essential oils (EOs) and mixture from two well-known plants (Syzygium aromaticum and Pelargonium graveolens) were tested for in vivo antioxidant and anti-inflammatory activities. The chemical analysis of the investigated Oils has lead to the identification of Eugenol (74.06%), Caryophyllene (11.52%) and Carvacrol acetate (7.82%) as the major element in S. aromaticum; while P. graveolens was much higher in Citronellol (30.77%), 10-epi-γ-Eudesmol (22.59%), and Geraniol (13.95%). In our pharmacological screening, both EOs demonstrated good antioxidant effects; especially S. aromaticum activity was much higher. In contrast, the in vivo investigation of the antioxidant activity using antioxidant enzymes (MDA, SOD and CAT) in the protozoa model (Tetrahemena pyriformis) demonstrated a higher protective effect of P. graveolens and EOs mixture. On the other hand, EOs demonstrated anti-inflammatory effect on the two phases of inflammation in the carrageenan induced edema model. Results from this study indicate that EOs from S. aromaticum and P. Graveolens can be used as a multitarget therapy.