Effects of Olea oleaster leaf extract and purified oleuropein on ethanol-induced gastric ulcer in male Wistar rats.

Objectives: Evaluating the effect of fresh Oleaster leaf extract (OLE) and purified oleuropein (OLR) on ethanol-induced gastric ulcers in rats. HPLC analysis demonstrates the presence of various polyphenol compounds such as ligstroside, luteolin derivative, oleuropein, and comselogoside. Materials and Methods: Gastric ulcer was induced by administration of ethanol by the gastric gavage route. The olive leaf extract was analyzed by HPLC-PDA-ESI-MS, and OLR was purified. These two compounds were given 2 hr before gastric ulcer induction by ethanol. Results: This study verified that OLE and purified OLR protect from ethanol-induced gastric ulceration and damage, evidenced by the significant decrease in gastric ulcer urea (by 74 and 58% respectively) and stomach mucus content (by 169 and 87% respectively). In addition, the ulcer index (UI) and curative index (CI) levels in the stomach of the rats treated with this supplement were also suppressed by 55 and 46%, respectively. OLE and OLR also decreased the gastric myeloperoxidase (MPO) activity and ameliorated the nitric oxide (NO) content. OLE and OL also ingestion suppressed gastric tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) rates. Macroscopic and histological findings revealed that OLE and OLR protect from gastric hemorrhage, severe disruption of the gastric mucosa, and neutrophil infiltration. Conclusion: Overall, the findings demonstrate that OLE and OLR have both promising potential with regard to the inhibition of gastric hemorrhage and lesions.

Design of a new palladium(ii) halide complex as a bio-active material: synthesis, physico-chemical studies, DFT-computations and evaluation of anti-inflammatory, antioxidant and anti-gastric damage activities.

Colorless single crystals of the zero-dimensional hybrid compound, (C6H10N2)2[PdCl6]·2H2O were acquired through the slow evaporation technique. The crystal structure was explored using SC-XRD, which demonstrates that the material crystallizes in the centrosymmetric space group P1̄ of the triclinic system. The density functional theory method at the B3LYP/Lan2mb basis set level was employed to establish the optimized geometry and vibrational frequencies of the title compound. An acceptable correspondence was observed between the results obtained through calculation and the experimental data, including the structure, and IR spectra. The optical characteristics revealed a direct band gap energy of 2.35 eV, validating the semiconductor characteristics of this new material. The results suggest strong agreement with the experimental data and validate the involvement of metal orbitals in defining the HOMO-LUMO boundary. Simultaneous TGA-DTA shows that this material remains solid up to 210 °C. Beyond these temperatures, a gradual decomposition process occurs, extending up to 440 °C and unfolding in several steps. This process entails the liberation of diverse compounds, encompassing organic molecules, and the evaporation of chlorine ions, ultimately leading to the formation of palladium oxide (PdO) as the final product. When given to rats with gastric ulcers at a dose of 100 mg kg-1, these compounds inhibit the key enzyme responsible for neutrophil infiltration as myeloperoxidase (MPO) by 38.7%. The compound also alleviates cellular damage induced by free radicals, demonstrated by a notable 48.3% decrease in thiobarbituric acid reactive substance rates (TBARS) compared to untreated rats. Additionally, these compounds bring about a substantial 30.6% reduction in the surface area of ulcers.

Antiobesity and antidiabetes effects of Cyperus rotundus rhizomes presenting protein tyrosine phosphatase, dipeptidyl peptidase 4, metabolic enzymes, stress oxidant and inflammation inhibitory potential.

Diabetes is a significant global health concern that increases the vulnerability to various chronic illnesses. In view of this issue, the current research aimed to examine the effects of administering an extract derived from the tubers of Cyperus rotundus L (CrE) on obesity, type 1 diabetes, and liver-kidney toxicity. Through the utilization of HPLC-DAD analysis, it was discovered that the extract contained several components, including quercetin (47.8%), luteolin glucoside (17%), luteolin (7.56%), apigenin-7-glucoside (6.29%), naringinin (4.52%), and seven others. In vitro experiments they have demonstrated that CrE effectively inhibited key digestive enzymes associated with obesity and type 2 diabetes, such as DPP-4, PTP1B, lipase, and α-amylase, as evidenced by their respective IC50 values are about 23, 51,83, and 67 µg/ml respectively. Furthermore, when diabetic rats were administered CrE, the activity of pancreatic enzymes linked to inflammation, namely 5-lipoxygenase (5-LO), hyaluronidase (HAase), and myeloperoxidase (MPO), was significantly suppressed by 48, 41, 75, and 47%, respectively. Moreover, CrE exhibited protective effects on pancreatic ß-cells by inhibiting the formation of thiobarbituric acid reactive substances (TBARS) by 65% and the induction of superoxide Dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities by 62, 108, and 112% respectively as compared to diabetic untreated rat. Additionally, CrE significantly inhibited the activities of intestinal, pancreatic, and serum lipase and α-amylase activities. In diabetic rats, CrE administration suppressed glycogen phosphorylase (GP) stimulated glycogen synthase (GS) activities by 45 and 30%; and this increased liver glycogen content by 45%. Furthermore, CrE modulated key hepatic enzymes involved in carbohydrate metabolism, including hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6P), and fructose-1,6-bisphosphatase (FBP). Notably, the average food and water intake (AFI and AWI) of diabetic rats treated with CrE was reduced by 15 and 16% respectively as compared to those without any treatment. Therefore, this study demonstrated the effectiveness of Cyperus rotundus tubers in preventing and treating obesity and diabetes.

Fructooligosaccharides from Cynoglossum tubiflorus: Effect of the molecular size on their antidiabetic activity in high-fat diet and alloxan induced diabetic rats.

The use of acetylation followed by silica gel column purification allowed the isolation of eight fructooligosaccharides (FOS) from the ethanol extract of Cynoglossum tubiflorus roots. Each FOS was identified by analyzing its FT-IR, HRMS/MS and NMR data, including 1H, 13C and 2D NMR HH COSY, HMBC and NOESY. In diabetic rats treated with a series of FOS from Glc-(Fru)3 to Glc-(Fru)7, a significant inhibition of intestinal α-amylase was observed. This activity increases proportionally with the FOS molecular size. It was found that they delay the absorption of total cholesterol (TC), ldl-cholesterol (LDL-C) and increase HDL-cholesterol (HDL-C) in a molecular size-dependent manner. This inhibitory effect on the activity of the digestive enzyme causes a significant (p < 0.05) reduction in the level of glucose in the blood as an anti-diabetic action. The ethanolic extract (E.E) exerts a significant effect against α-amylase as well as antihyperglycemic and antihyperlipidemic actions, while its acetylation suppresses these effects. Therefore, this study demonstrates for the first time that pure FOS act as an efficient agent in preventing hyperglycemia and hyperlipidemia and that this action evolves in the same manner with their molecular size.

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities.

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC50 = 1.09 mg/mL and IC50 = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC50 = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.

Design, synthesis and biological evaluation of new 1,ω-Bis-(5-alkyl-3-tosyl-1,3,4,2-triazaphospholino)alkanes as in vitro α-amylase and lipase inhibitors.

A series of new 1,ω-bis-(5-alkyl-3-tosyl-1,3,4,2-triazaphospholino)alkanes 2 and 3 were obtained in excellent yields by the condensation of 1,ω-bis-(1-tosylamidrazone)alkanes 1 with two equivalent molars of Lawesson's Reagent (LR) and trisdimethylaminophosphine, respectively. All synthesized compounds were characterized by various spectroscopic techniques including IR, 1H NMR, 13C NMR and 31P NMR and elemental analysis. The newly synthesized compounds were evaluated against key enzymes related to diabetes and obesity such as α-amylase and lipase. This study showed that the compounds 3a and 2b are an excellent inhibitor of α-amylase (with IC50 = 18.8 mM) and lipase (with IC50 = 19 mM) respectively, as compared with standard, orlistat (IC50 = 22 mM). Among this series, compounds 3a and 2b with the CH3 or C2H5 group at position 6 were identified as the most potent inhibitors against α-amylase, and lipase enzymes. The remaining compounds were found to be moderately active. Further, molecular docking simulation studies were done to identify the interactions and binding mode of synthesized analogs at binding site of α-amylase and lipase enzymes.

The Use of D-Optimal Mixture Design in Optimizing Formulation of a Nutraceutical Hard Candy.

The aim of this study was to optimize the formulation of hard candy with antiviral herbal extracts and flowered with Citrus limon peel essential oils. To substitute water fraction, the D-optimal mixture design was used. The optimized mixture fractions of the best hard candy formulation contain Curcuma longa extract (10%), Artemisia herba-alba Asso extract (3.33%), Glycyrrhiza glabra extract (1.66%), and Zingiber officinale extract (1.66%) and flowered by 20 µL/100 gram of Citrus limon essential oils. The effect of the addition had been investigated on the sensory, physicochemical, and phytochemical of the hard candy according to the optimal formulation. The main component of Citrus limon essential oil is limonene (52.47%), which has a pleasant lemon fragrance. The mixture of herbal extract added increased the total phenols, the flavonoid, and the ash content of the formulated hard candy (10.90 ± 0.50 mg GAE/g, 0.054 ± 0.02 mg CE/g, and 0.018 ± 0.009, respectively). The measurement of the DPPH free radical activity reveals a good antioxidant activity (26.4%). Furthermore, the sensory analysis has shown a good appreciation. Thus, formulated hard candy is a sensorially and therapeutically interesting product.

Ephedra alata subsp. alenda (Ephedraceae) leaf extracts: phytochemical screening, anti-diabetic, anti-obesity and anti-toxic activities on diabetic-induced liver-kidney-testes toxicities and inhibition of α-amylase and lipase enzymes.

The study evaluated the phytochemical composition of Ephedra alata and its effects on α-amylase and lipase enzymes and diabetic-induced liver-kidney-testes toxicities to determine the anti-diabetic, anti-obesity, and anti-toxic potentials of the plant. Obesity was induced by a high-fat and fructose diet (HFFD). Various compounds were identified and quantified: cafeic acid, apigenin 7-O-glucoside, apigenin, rutin, luteolin 7-O-glucoside, p-Coumaric acid and others in EA aqueous extract (EAWE). In vitro, this study showed that EAWE strongly inhibited lipase activity as compared to EA methanol (EAME) and ethyl acetate EA extracts (EAEE). In obese rats, the supplementation of EAWE inhibited significantly (P < 0.01) intestinal and pancreatic lipase activity by 35 and 36% respectively. This decrease in lipid digestive enzyme activity caused a significant (P < 0.05) reduce in the weight gain by 12.7% and significant (P < 0.05) decrease in the serum lipid rate as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Moreover, the supplementation of EAWE to obese rats reduced the activity of α-amylase in the small intestine and pancreas by 26 and 31% respectively (P < 0.01) and consequently decreases in serum glucose level by 20.8% (P < 0.05). In addition, administration of EAWE in type 2 diabetes protected from obesity induced liver, kidney and testes alterations. The potent protective effect EAWE may be influenced by the diversity of phenolic compounds. therefore, this study showed in the first time that EAWE are efficient for the prevention and the amelioration of obesity, hyperglycemia, and various organs toxicities.

Globularia alypum Extracts Attenuate Hyperglycemia and Protect against Various Organ Toxicities in Alloxan-Induced Experimental Diabetic Rats.

In this study, we attempted for the first time to determine the phytochemical compositions and biopharmaceutical properties of Globularia alypum methanol extract (GAME) and Globularia alypum water extract (GAWE). High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis was performed to establish the chemical profile of the investigated extracts. Chemical composition analysis was taken in the presence of various bioactive compounds such as quercetin 7-O-glucoside and apigenin 7-O-glucoside in GAME. In GAWE, various abundant compounds were found in the extract such as quercetin 7-O-glucoside, apigenin, quercetin, apigenin 7-O-glucoside, and cinnamic acid. This study showed that the administration of GAWE and GAME to type 1 diabetic rats decreased fasting blood glucose, protected pancreas ß-cells from death and injury, increased liver glycogen rate, and ameliorated oral glucose tolerance test. Moreover, GA reduced weight loss, and diabetes decreased basic physical activity. In addition, the administration of GA extracts in diabetic rats protected from diabetes-induced liver, kidney, testes, heart, and bone toxicities. Conclusion. GAWE has possible value for antidiabetic oral medication.

Anti-obesity, anti-hyperglycaemic, anti-antipyretic and analgesic activities of Globularia alypum extracts.

OBJECTIVES: The aim of this study is to evaluate the anti-obesity, anti-hyperglycaemic, analgesic and antipyretic activities of Globularia alypum (GA). MATERIALS AND METHODS: GA methanol and water extracts (GAME, GAWE) were administered to high-fat-high-glucose diet (HFFD) rats. RESULTS: This study showed that GAME exhibited the highest antioxidant, anti-α-amylase and anti-lipase activities, with half inhibitory concentration (IC50) values 0.067, 1.05 and 2.97 mg/ml respectively. In HFFD rats, the administration of GAME inhibited lipase activity by 36, 37 and 30% in the intestine, pancreas and serum, respectively, reduced body weight by 17.7% and modulated lipid profile. In addition, administration of GAME to HFFD-rats decreased α-amylase activity, improved glucose level and protected liver function. Furthermore, the administration of GA extracts to rats revealed antipyretic (reduction in writhing by 64%) and analgesic (decrease of temperature by 1.11 °C) activities. CONCLUSION: This study showed that GA extracts exhibited an anti-obesity, anti-hyperglycaemia, anti-pyretic and analgesic activities.

Diversity-Oriented Synthesis of Spiropyrrolo[1,2-a]isoquinoline Derivatives via Diastereoselective and Regiodivergent Three-Component 1,3-Dipolar Cycloaddition Reactions: In Vitro and in Vivo Evaluation of the Antidiabetic Activity of Rhodanine Analogues.

An efficient diastereoselective route is developed to get access to novel spiropyrrolo[1,2-a]isoquinoline-oxindole skeletons by a one-pot three-component [3 + 2] cycloaddition reaction of (Z)-5-arylidene-1,3-thiazolidine-2,4-diones, isatin derivatives, and 1,2,3,4-tetrahydroisoquinoline (THIQ). Interestingly, the regioselectivity of the reaction is both temperature- and solvent-dependent, allowing the synthesis of two regioisomeric endo-dispiropyrrolo[2,1-a]isoquinolineoxindoles in excellent yield. Unprecedentedly, each isomeric dispiropyrrolo[2,1-a]isoquinolineoxindole endured retro-1,3-dipolar cycloaddition/recycloaddition reactions under thermal or catalytic conditions to regenerate the corresponding regioisomeric counterpart. In addition, DFT calculations were performed at the M062X/6-31++g(d,p) level of theory to unravel the origin of the reversal of regioselectivity and endo-stereoselectivity of the title 1,3-dipolar cycloaddition reactions. Upon treatment of Isatin, THIQ with (Z)-4-arylidene-5-thioxo-thiazolidin-2-ones as dipolarophiles, unusual rhodanine analogues were formed, along with smaller amounts of a dispirooxindole-piperazine. The structure and the relative configuration of these N-heterocycles were unambiguously assigned by spectroscopic techniques and confirmed by four single-crystal structures. In vitro and in vivo studies reveal that the novel rhodanine derivatives exert antidiabetic activity. The binding affinity with the active site of the enzyme α-amylase was studied by molecular docking. Furthermore, the bioavailability assessed through virtual ADME parameters (Absorption, Distribution, Metabolism, Elimination pharmacokinetics) and the excellent fit with the Lipinski and Veber rules predict good drug-likeness properties for a bromo-substituted 2-sulfanylidene-1,3-thiazolidin-4-one.

Antihyperlipidemic, Antihyperglycemic, and Liver Function Protection of Olea europaea var. Meski Stone and Seed Extracts: LC-ESI-HRMS-Based Composition Analysis.

Methanol and methanol/water extracts of olive stones and seeds from Olea europaea var. meski were analyzed by reversed-phase high-performance liquid chromatography (HPLC) with diode array detection and mass spectrometry (LC-MS/MS). A total of 28 metabolites were identified; among them are hydroxycinnamic acid derivatives, phenolic alcohols, flavonoids and flavonoid glucosides, secoiridoids, and terpenes. All the extracts were screened for the inhibitory effect of key enzymes related to diabetes and obesity, such as α-amylase and lipase. An in vitro study revealed that Olea meski stone ethanol (MSE) and methanol (MSM) extracts and Olea meski seed ethanol (MSE1) and methanol (MSM1) extracts exert an inhibitory action against lipase and α-amylase. The most potent activity was observed in the StM extract with IC50 equal to 0.19 mg/ml against DPPH oxidation, 1.04 mg/ml against α-amylase, and 2.13 mg/ml against lipase. In HFFD rats, the findings indicated that the increase of body weight, LDL, TC, and glucose levels and then the decrease in HDL-C were significantly suppressed in the MSM-treated group than those in HFFD rats. Moreover, the MSM extract exhibited a prominent selective inhibitory effect against intestinal lipase and α-amylase activities. The MSM extract was also able to protect the liver-kidney functions efficiently, which was evidenced by biochemicals and histological studies.

Synthesis, antidiabetic activity and molecular docking study of rhodanine-substitued spirooxindole pyrrolidine derivatives as novel α-amylase inhibitors.

In a sustained search for novel α-amylase inhibitors for the treatment of type 2 diabetes mellitus (T2DM), we report herein the synthesis of a series of nineteen novel rhodanine-fused spiro[pyrrolidine-2,3'-oxindoles]. They were obtained by one-pot three component [3 + 2] cycloaddition of stabilized azomethine ylides, generated in situ by condensation of glycine methyl ester and the cyclic ketones 1H-indole-2,3-dione (isatin), with (Z)-5-arylidine-2-thioxothiazolidin-4-ones. The highlight of this protocol is the efficient high-yield construction of structurally diverse rhodanine-fused spiro[pyrrolidine-2,3'-oxindoles] scaffolds, including four contiguous stereocenters, along with excellent regio- and diastereoselectivities. The stereochemistry of all compounds was confirmed by NMR and corroborated by an X-ray diffraction study performed on one derivative. All cycloadducts were evaluated in vitro for their α-amylase inhibitory activity and showed good α-amylase inhibition with IC50 values ranging between 1.49 ± 0.10 and 3.06 ± 0.17 µM, with respect to the control drug acarbose (IC50 = 1.56 µM). Structural activity relationships (SARs) were also established for all synthesized compounds and the binding interactions of the most active spiropyrrolidine derivatives were modelledby means of molecular insilico docking studies. The most potent compounds 5 g, 5 k, 5 s and 5 l were further screened in vivo for their hypoglycemic activity in alloxan-induced diabetic rats, showing a reduction of the blood glucose level. Therefore, these spiropyrrolidine derivatives may be considered as promising candidates for the development of new classes of antidiabetic drugs.

Occurrence of 40 pharmaceutically active compounds in hospital and urban wastewaters and their contribution to Mahdia coastal seawater contamination.

In the present study, the occurrence of 40 pharmaceuticals belonging to several therapeutic groups was investigated for the first time in hospital effluent, wastewater treatment plant influent and effluent, and seawater in Mahdia, Tunisia. Forty-six samples were collected within a 6-month sampling period. Pharmaceuticals were analyzed using solid-phase extraction followed by ultra-performance liquid chromatography-triple quadrupole mass spectrometry. Thirty-three out of the forty target compounds were detected over a wide concentration of ranges, from nanograms per liter to micrograms per liter, depending on the type of sample. Maximum values were detected for caffeine at 902 µgL-1 in hospital wastewater. This compound, as well as salicylic acid, sulfadiazine, and sulfamethizole, were detected in all samples. The average concentration of total pharmaceuticals in hospital wastewater (340 µgL-1) was higher than those detected in influent and effluent wastewater and seawater (275.11 and 0.2 µgL-1, respectively). Risk quotients (RQs) were also estimated to provide a preliminary environmental risk assessment and results revealed that sulfadiazine, sulfamethoxazole, and fluoxetine could pose medium/high risk to the tested aquatic organisms for maximum measured concentrations in wastewater (including hospital and WWTP samples). Although the measured environmental concentrations (MECs) detected in seawater samples might not pose a toxic effect to the aquatic organisms (except for salicylic acid, sulfamethoxazole and fluoxetine), further researches are needed due to the continuous release of wastewater in the environment and the limited efficiency of wastewater treatment processes.

Imipenem toxicity in male reproductive organs as a result of inflammatory microenvironment and oxidative stress in germinal cells.

Imipenem is a beta-Lactam antibiotic characterized by a broad spectrum of activity. It is prescribed to treat severe infections. Our goal is to investigate toxicity induced in male rat reproductive systems following exposure to this drug (15, 50 or 100 mg/kg) compared to gentamicin (50 mg/kg) treatment. Effects of imipenem on reproductive organ weights, histoarchitecture, sperm parameters, and oxidative stress parameters were evaluated. Serum testosterone levels were measured. Apoptosis and inflammatory behaviors were investigated by immunohistochemical proteins expression analysis of apoptosis regulator BAX (Bax), B-cell lymphoma 2 (Bcl-2), and interleukin-1 beta (IL-1 beta) in testis. Results showed a significant decrease in male fertility parameters including sperm count, sperm motility, reproductive organ weights and serum testosterone levels after imipenem administration as compared to the control and gentamicin treated groups. Increased sperm abnormality was significant in animals treated with high doses of imipenem. Oxidative stress analysis revealed an expressed increase in lipid peroxidation and carbonyl groups levels in testicular tissues compared to control. Similar results were observed with superoxide dismutase and catalase activities from testicular tissues. In addition, severe testicular lesions were observed in the seminiferous tubules as well as important impairments in spermatogenesis testifying an inflammatory microenvironment confirmed by the intensive expression of IL1-beta and Bax protein by germinal cells and Bcl-2 by Leydig cells. In conclusion, imipenem treatment with high doses was found to lead to oxidative stress in male reproductive organs and an inflammatory microenvironment leading to spermatogenesis dysfunction and histopathological changes in the testis.

Phytoestrogens inhibit key-enzymes linked to obesity, type 2 diabetes and liver-kidney toxicity in high fructose-fat diet in mice.

Objective: To evaluate the effect of the administration of phytoestrogens on obesity, type 2 diabetes, and liver-kidney toxicity. Methods: Phytoestrogens (phyto(E2)) were administrated to high fructose-fat diet (HFFD). Results: This study showed that administration of phyto(E2) to HFFD-mice inhibited lipase activity by 34%, decreased body weight by 20% and modulated lipid profile, showed a decrease in total-cholesterol (TC) and LDL-cholesterol (LDL-C) rates in the plasma by 59% and 42%, respectively, and increased the HDL-cholesterol (HDL-C) level by 31%. In addition, the administration of phytoestrogens to HFFD-mice exerts an inhibitory effect on α-amylase activity and decreased glucose level by 28% and increase in liver glycogen level by 33%; and ameliorate oral glucose tolerance test. Conclusions: This study demonstrate that phyto(E2) has both a promising potential with regards to the inhibition of intestinal lipase and α-amylase activities, and a valuable hypoglycemic and hypolipidemic function.

The cruciferous Diplotaxis simplex: Phytochemistry analysis and its protective effect on liver and kidney toxicities, and lipid profile disorders in alloxan-induced diabetic rats.

BACKGROUND: Type 2 diabetes mellitus is a prevalent systemic disease affecting an important proportion of the population worldwide. It has been suggested that excessive reactive oxygen species generation and therefore development of an oxidative stress status is a key factor leading to diabetic complications. Accordingly, it seems that medicinal plants can offer a wide range of new antidiabetic drugs. Diplotaxis simplex (Viv.) Spreng. (Brassicaceae) is an edible plant largely distributed in the Mediterranean region. D. simplex flowers display important in vitro antioxidant potential and inhibitory activity of the α-glucosidase, a key enzyme linked to type 2 diabetes mellitus. In this paper, the antihyperglycemic potential of D. simplex flowers on diabetic rats were investigated. METHODS: Bioactive substances were determined by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS) analysis. Animals were divided into four groups of six rats each: a normal control group, a diabetic control group, a diabetic group receiving flowers extract (200 mg/kg body mass) and a diabetic group receiving acarbose (10 mg/kg body mass) as standard drug. RESULTS: Many glycosides of rhamnetin, isorhamnetin, quercetin and kaempferol compounds were identified in the ethanolic flowers extract. Alloxan induced hyperglycemia, manifested by a significant (p < 0.05) increase in the blood glucose level as well as in serum α-amylase activity. Furthermore, diabetic rats exhibited oxidative stress, as evidenced by a decrease in antioxidant enzymes activities and an increase in lipid peroxidation level of the pancreas, liver and kidneys. Interestingly, the oral administration of D. simplex flowers extract during 30 days restored the glycemia, α-amylase activity, serum lipid profile and antioxidant enzymes. Moreover, the flowers extract exhibited a renal protective role by decreasing the urea and creatinine levels in diabetic rats serum. CONCLUSIONS: D. simplex flowers contained bioactive compounds that possess important antioxidant and hypoglycemic properties and protected pancreas, liver and kidneys against hyperglycemia damage.

Modulatory Effect of an Isolated Triglyceride from Fenugreek Seed Oil on of α-Amylase, Lipase and ACE Activities, Liver-Kidney Functions and Metabolic Disorders of Diabetic Rats.

This study was designed to examine physicochemical characteristics, chemical compositions and biological activities of fenugreek seed oil (FSO) and its pure triglyceride (TG). One fenugreek TG was purified using a bioassay-guided fractionation and administrated to surviving diabetic rats. The free fatty acids percentage as well as, the peroxide, the saponification and the iodine values were 2%, 12 mequiv. O2/kg of oil, 189 (mg KOH/g) and 110 (g/100 g of oil), respectively. Linolenic acid (C18:3 26.14%), Linoleic acid (C18:2 41.13%) and Oleic acid (C18:1 17.07%) were the dominant fatty acids in the FSO. ß-sitosterol was the major sterol (85.3%) in the FSO. LnLnO (17.1%), LLL (16.6%), OLL and OOLn (8.4%), were the abundant triglycerides. The hexane extract of fenugreek seed (exhibiting the powerful inhibitory activity against alpha-amylase) was purified using a bioassay-guided fractionation affording one fenugreek TG: (11Z)-11- eicosenoic acid 2, 3- bis[((9Z, 12Z, 15Z)-1-oxo-9, 12, 15-octadecatrien-1-yl)oxy] propyl ester. In diabetic rats, the administration of the fenugreek TG inhibited α-amylase activity in small intestine by 36% as compared to untreated diabetic rats. Moreover, fenugreek TG increased insulin sensibility which leads to decrease in blood glucose level by 43%. In addition, this study demonstrated that administration of pure fenugreek TG to diabetic rats ameliorated the glycogen rate in liver and muscle. In addition, the administration of fenugreek TG reverted back the activity of angiotensin converting enzyme respectively in kidney and plasma by 33 and 29%. Interestingly, the fenugreek TG inhibited lipase activity in small intestine by 33% which leads to the regulation of lipid profile. Moreover, the fenugreek TG protected liver-kidney function evidenced by histological study. In conclusion, our finding demonstrates that the administration of fenugreek TG to diabetic rats can make it a potential candidate for industrial application as a pharmacological agent for the treatment of hyperglycemia.

Evaluation of Bacillus subtilis SPB1 biosurfactant effects on hyperglycemia, angiotensin I-converting enzyme (ACE) activity and kidney function in rats fed on high-fat-high-fructose diet.

This study investigated the protective and the curative effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant in alleviating induced obesity complications in rats fed on high-fat-high-fructose diet (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet-fed rats (CD), HFFD-fed rats, HFFD-fed rats supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD + Bios1), rats fed on HFFD receiving standard drug (HFFD + Torva), or SPB1 biosurfactant (HFFD + Bios2) during the last 4 weeks of the study. HFFD induced hyperglycemia, manifested by a significant (p < 0.001) increase (20%) in the levels of glucose and α-amylase activity in the plasma, when compared with CD. The administration of SPB1 biosurfactant to rats fed on HFFD reverted back normal blood glucose and α-amylase activity levels. Also, the findings clearly showed that acute oral administration of SPB1 biosurfactant reduced significantly (34%) the peak of blood glucose concentration 60 min after glucose administration, as compared with untreated rats fed on HFFD. Furthermore, renal dysfunction indices such as creatinine and urea as well as the level of angiotensin I-converting enzyme (ACE) exhibited remarkable increases in serum of rats fed on HFFD by 28.35%, 46%, and 92%,. Interestingly, SPB1 lipopeptides treatments decreased the creatinine and urea levels significantly (p < 0.001) near normal values, as compared with that of the HFFD group, and also showed an improvement of the kidney cortex architecture. Moreover, SPB1 biosurfactant displayed a potent inhibition of ACE activity in vitro (CI50 value= 1.37 mg/mL) as well as in vivo in obese rats by 42% and 27.25% with HFFD + Bios1 and HFFD + Bios2 treatments, respectively, and comparatively with the HFFD group. Besides, SPB1 lipopeptides treatments improved some of serum electrolytes such as Na+, K+, Ca2+ , and Mg2+. The results showed that SPB1 lipopeptide biosurfactant presented useful hypoglycemic and antihypertensive properties, and was able to alleviate renal lipid deposition in rats fed on a hypercaloric diet.

Protective and curative effects of Bacillus subtilis SPB1 biosurfactant on high-fat-high-fructose diet induced hyperlipidemia, hypertriglyceridemia and deterioration of liver function in rats.

This study was aimed to assess the plausible anti-obesity effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant on high fat high fructose diet-fed rats (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet (CD), HFFD, HFFD supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD+Bios1, 10mg/kg/day), HFFD receiving standard drug (HFFD+Torva, 10mg/kg/day) or SPB1 biosurfactant (HFFD+Bios2, 10mg/kg/day) during the last 4 weeks of the study. The results showed an increase in body weight of HFFD by ∼19% as compared to controls (CD). Moreover, serum lipase activity underwent a threefold increase which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG) and LDL-cholesterol (LDL-Ch) in serum of untreated HFFD, as well as a rise in the calculated atherogenic index (AI). Furthermore, liver dysfunction indices such as AST, ALT, CPK, LDH, GGT, ALP and T-Bilirubins exhibited remarkable increases in serum of HFFD as compared to controls (CD). Whereas, the administration of Bacillus subtilis SPB1 biosurfactant to HFFD improved the body weight gain and serum lipids profile and reverted back near normal the activities of lipase and liver toxicity indicators. In addition, notable protective and curative effects were reported in liver tissues. Overall, these results suggest that the lipopeptides biosynthesized by Bacillus subtilis SPB1 achieved an anti-obesity effect through the inhibition of lipid digestive and liver dysfunction enzymes.