Geniposide and Harpagoside Functionalized Cerium Oxide Nanoparticles as a Potential Neuroprotective.

Alzheimer's disease is associated with protein aggregation, oxidative stress, and the role of acetylcholinesterase in the pathology of the disease. Previous investigations have demonstrated that geniposide and harpagoside protect the brain neurons, and cerium nanoparticles (CeO2 NPs) have potent redox and antioxidant properties. Thus, the effect of nanoparticles of Ce NPs and geniposide and harpagoside (GH/CeO2 NPs) on ameliorating AD pathogenesis was established on AlCl3-induced AD in mice and an aggregation proteins test in vitro. Findings of spectroscopy analysis have revealed that GH/CeO2 NPs are highly stable, nano-size, spherical in shape, amorphous nature, and a total encapsulation of GH in cerium. Treatments with CeO2 NPs, GH/CeO2 NPs, and donepezil used as positive control inhibit fibril formation and protein aggregation, protect structural modifications in the BSA-ribose system, have the ability to counteract Tau protein aggregation and amyloid-ß1-42 aggregation under fibrillation condition, and are able to inhibit AChE and BuChE. While the GH/CeO2 NPs, treatment in AD induced by AlCl3 inhibited amyloid-ß1-42, substantially enhanced the memory, the cognition coordination of movement in part AD pathogenesis may be alleviated through reducing amyloidogenic pathway and AChE and BuChE activities. The findings of this work provide important comprehension of the chemoprotective activities of iridoids combined with nanoparticles. This could be useful in the development of new therapeutic methods for the treatment of neurodegenerative diseases.

Diterpenes from seeds of Phalaris canariensis and their PTP1B inhibitory activity and hypoglycemic effects in streptozotocin-induced diabetic mice.

This present study was to evaluate the protein tyrosine phosphatase 1B (PTP1B) inhibitory activity of nine diterpenes isolated from seeds of Phalaris canariensis, as well as their effect on streptozotocin-nicotinamide-induced type 2 diabetic mice. Their structures were established by spectroscopic analyses. Diterpenes, 1, 4, and 2 exhibited the strongest inhibitory activity on PTP1B with IC50 values of 6.9, 7.3, and 6.5 µM, respectively, The administration of 1-9 showed significant effect on hyperglycemia, among them 1, 4, and 2 reduced fasting glucose levels (55.65%, 54.27%, and 51.22%, respectively). Results revealed that diterpenes performed potential antidiabetic activity via inhibition of PTP1B.[Formula: see text].

3'-O-ß-d-glucopyranosyl-α,4,2',4',6'-pentahydroxy-dihydrochalcone, from Bark of Eysenhardtia polystachya Prevents Diabetic Nephropathy via Inhibiting Protein Glycation in STZ-Nicotinamide Induced Diabetic Mice.

Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3'-O-ß-d-glucopyranosyl α,4,2',4',6'-pentahydroxy⁻dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p < 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.

Phylogenomics of 2,4-Diacetylphloroglucinol-Producing Pseudomonas and Novel Antiglycation Endophytes from Piper auritum.

2,4-Diacetylphloroglucinol (DAPG) (1) is a phenolic polyketide produced by some plant-associated Pseudomonas species, with many biological activities and ecological functions. Here, we aimed at reconstructing the natural history of DAPG using phylogenomics focused at its biosynthetic gene cluster or phl genes. In addition to around 1500 publically available genomes, we obtained and analyzed the sequences of nine novel Pseudomonas endophytes isolated from the antidiabetic medicinal plant Piper auritum. We found that 29 organisms belonging to six Pseudomonas species contain the phl genes at different frequencies depending on the species. The evolution of the phl genes was then reconstructed, leading to at least two clades postulated to correlate with the known chemical diversity surrounding DAPG biosynthesis. Moreover, two of the newly obtained Pseudomonas endophytes with high antiglycation activity were shown to exert their inhibitory activity against the formation of advanced glycation end-products via DAPG and related congeners. Its isomer, 5-hydroxyferulic acid (2), detected during bioactivity-guided fractionation, together with other DAPG congeners, were found to enhance the detected inhibitory activity. This report provides evidence of a link between the evolution and chemical diversity of DAPG and congeners.

Inhibition by Seeds of Phalaris canariensis Extracts of Key Enzymes Linked to Obesity.

CONTEXT: Obesity and its associated diseases are an increasing problem around the world. One hyperglycemic remedy is reduction of glucose absorption performed by suppressing digestion of carbohydrates and lipids through the use of inhibitors. Phalaris canariensis (P canariensis) is a species belonging to the Graminaceae family and is used in traditional medicine in Mexico for treatment of diabetes and obesity. OBJECTIVE: The aim of the study was to evaluate the effects of different extracts of the seeds of P canariensis on enzymes metabolizing fat and carbohydrates, obtained using 3 solvents. DESIGN: The seeds of P canariensis were extracted using hexane (ALH), chloroform (ALC), and methanol (ALM) and were investigated for their antiobesity potential. SETTING: This research was conducted in the Laboratory of Research of Natural Products in the School of Chemical Engineering at the National Polytechnic Institute and in the Research Laboratory of Enzymology in the National School of Biological Sciences. OUTCOME MEASURES: Different concentrations of the extracts were used to study the inhibition of enzymatic activity by porcine pancreatic α-amylase, with carbose as a positive control. The inhibitory activity of α-glucosidase was determined using the standard method with bovine serum albumin (BSA). Pancreatic lipase (PL) activity was measured by absorbance at 412 nm, and the data obtained were compared with orlistat. The PL activity was assessed using a second method measuring the rate of release of oleic acid from triolein. Lipoprotein lipase (LPL) activity was measured by released (3H)-oleic acid. Lipolytic activity in cultured, mouse, 3T3-Ll adipocytes was used as a measure of hormone-sensitive lipase activity. The inhibitory activity of rat intestinal sucrase was determined by measuring the glucose released. A Caco-2 cell assay determined the content of free glucose. RESULTS: The ALH extract of P canariensis showed potent inhibitory activity with IC50 values of 2.13 and 1.25 mg/mL as compared with α-amylase and α-glucosidase, respectively, and produced inhibition in rat intestinal sucrose. Further, the ALM extract showed significantly inhibitory effects against PL, LPL, and lipolysis of 3T3-LI adipocytes. CONCLUSIONS: The results provide evidence for the effects of the seeds of P canariensis for a retarded absorption of carbohydrates and lipids through the inhibition of enzymes that are related to obesity and diabetes mellitus type 2.

Beneficial effect of Azadirachta indica on advanced glycation end-product in streptozotocin-diabetic rat.

CONTEXT: Both oxidation and hyperglycemia cause increased glycation and the formation of advanced glycation end-products (AGEs) which underlie the complications of diabetes. OBJECTIVE: The goal of this article is to determine the effect of the chloroform extract from leaves of Azadirachta indica A. Juss; (Meliaceae) (AI) on the formation of glycated protein. MATERIALS AND METHODS: Chloroform extract was subjected to in vitro bioassays to evaluate advanced glycation end-products formation. Bovine serum albumin (BSA)-glucose, BSA-methylglyoxal, Amadori-rich protein, glycated hemoglobin, oxidation, and glycation of LDL were determined. Doses of AI of 200 mg/kg/d by oral gavage were administered once daily for 30 d, at streptozotocin-induced diabetic rats. After this period, renal damage (TBARS), glucose, methylglyoxal, glycolaldehyde, and tail tendon collagen were investigated. RESULTS AND DISCUSSION: AI exhibits protective action in BSA against glycation formation, GHb, protein levels, and LDL against glycation and oxidation. The renal glucose level decreases a 3.9 mg/g wet tissue. TBA-reactive substance showed a significant decrease to 1.82 mmol/mg protein. In addition, AI showed inhibitory activity against AGEs formation, methylglyoxal, and glycolaldehyde levels in kidney. Treatment with AI in rat tail tendon produced a reduction in cross-linking of collagen proteins. The antiglycation activities of A. indica were attributed in part to their antioxidant activity. AI alleviated oxidative stress under diabetic conditions through the inhibition of lipid peroxidation prevents the onset renal damage. CONCLUSION: We found that A. indica is an inhibitor AGE formation, and oxidative stress with a renoprotective effect, which are considered to play important roles in diabetic kidney disease.

Anti-inflammatory activity of the hexane extract of Byrsonima crassifolia seeds in experimental animal models.

CONTEXT: Byrsonima crassifolia is a tropical tree, commonly known as nance and distributed widely in Mexico and Central and South America. Since pre- Hispanic times, the seeds of the fruits have been used in folklore medicine as an anti-inflammatory; however, currently no researchers have examined its potential pharmacological properties in scientific studies. OBJECTIVE: This study investigated the anti-inflammatory activity of extracts obtained with the solvents n-hexane, chloroform, and methanol from seeds of B crassifolia. DESIGN: The research team induced edemas in Wistar rats with 12-O-tetradecanoylphorbol (TPA), formaldehyde, carrageenan, and histamine to study the anti-inflammatory activity of the three organic extracts of seeds from B crassifolia. The team also used the cotton-pellet granuloma method to induce edemas in Wistar rats and study the inhibitory effect of the three extracts from B crassifolia. Finally, the team examined the participation of the nitric oxide (NO) system in the anti-inflammatory activity of the hexane extract of nance seeds (NS), diclorofenac, and L-NAME as well as the effects of L-arginine and D-arginine on the antiinflammatory actions of the compounds. SETTING: This research was conducted in the Laboratory of Research of Natural Products, School of Chemical Engineering, National Polytechnic Institute (IPNESIQIE) and Department of Biotechnology and Bioengineering, Cinvestav-IPN, Av. IPN 2508, Col. San Pedro Zacatenco, Mexico D.F., CP 07360, Mexico. OUTCOME MEASURES: The research team measured the edema that the solvents caused, either in the ears of rats for tetradecanoylphorbol or in the paws for formaldehyde, carrageenan, and histamine. To study the antiproliferative effects of the extracts after implantation of the cotton-pellet granuloma, the team determined the wet and dry weights of the pellets, after drying at 70°C for 1 hour in the second case. To study the participation of the NO system in the anti-inflammatory activity of the hexane extract of NS, diclofenac, and L-NAME, the research team measured paw edema. RESULTS: Among the extracts tested, NS showed the most significant anti-inflammatory activity. That extract decreased the paw edema that carrageenan, formaldehyde, histamine, and cotton pellet-induced, either by oral or topical administration at doses of 200 mg/kg, with 31%, 66%, 83%, and 58.2% inhibition respectively. In addition, NS inhibited the ear edema that TPA induced by 62%. Methanol and chloroform extracts produced a small effect, so the team does not present the results in this article. L-arginine, a precursor of NO, significantly inhibited the anti-inflammatory effects of NS and L-NAME, an anti-inflammatory drug, on mouse paw edema, but D-arginine did not. In contrast, neither D-arginine nor L-arginine inhibited the anti-inflammatory effects that diclofenac produced. These results indicate that the anti-inflammatory effect of NS on mouse paw edema occurs via the inhibition of NO production, as does the anti-inflammatory effect of L-NAME but not the anti-inflammatory effect of diclofenac. The anti-inflammatory activity of NS was comparable to standard anti-inflammatory drugs such as indomethacin, dexamethasone, and sodium diclofenac. CONCLUSIONS: The hexane extract from seeds of B crassifolia exhibited significant anti-inflammatory activity in both acute and chronic inflammatory models with a partial contribution of inhibitory actions on some cellular inflammatory responses. The anti-inflammatory mechanism of NS may be related to the other isoform (iNOS).

Meliacinolin: a potent α-glucosidase and α-amylase inhibitor isolated from Azadirachta indica leaves and in vivo antidiabetic property in streptozotocin-nicotinamide-induced type 2 diabetes in mice.

In India, Azadirachta indica is typically known as 'neem tree' and its leaves has long been used in the ayurvedic medical tradition as a treatment for diabetes mellitus. In-depth chromatographic investigation on chloroform extract resulted in identification of one new tetranortriterpenoid. Structural elucidation was established on the basis of spectral data as 24,25,26,27-tetranor-apotirucalla-(apoeupha)-1α-senecioyloxy-3α,7α-dihydroxy-14,20,22-trien-21,23-epoxy named by us as meliacinolin (1). The present study investigated the effect hypoglycaemic, hypolipidemic, oxidative stress, insulin resistance, α-glucosidase and α-amylase of 1 from A. indica. Diabetic rats were treated with 1 for 28 d and a set of biochemical parameters were studied including: glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. We also looked into liver function by determining glucose-6-phosphatase, glucokinase and hexokinase activities, and the effect on insulin level. While in vitro inhibition of α-glucosidase and α-amylase enzyme activities were used as indices of effect on glucose absorption. As a result we found that blood glucose level, serum biochemical parameters, hepatic enzymes, thiobarbituric acid reactive substances, and insulin level were restored in streptozotocin (STZ)-diabetic mice to normal levels with 1. Meliacinolin inhibited α-glucosidase and α-amylase activities. We conclude that meliacinolin can efficiently inhibit insulin resistance, improvement of renal function, lipid abnormalities, and oxidative stress, indicating that its therapeutic properties may be due to the interaction of meliacinolin with multiple targets involved in diabetes pathogenesis. α-Glucosidase and α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia prevents the digestion of carbohydrates.

Inhibition of Advanced Glycation End-Product Formation by Origanum majorana L. In Vitro and in Streptozotocin-Induced Diabetic Rats.

The development of AGE inhibitors is considered to have therapeutic potential in patients with diabetes diseases. The aim of the present study was investigate the effect of methanolic extract of the leaves of Origanum majorana (OM) used as spice in many countries on AGEs formation. In vitro studies indicated a significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal, an intermediate reactive carbonyl of AGE formation. The results demonstrate that OM have significant effects on in vitro AGE formation, and the glycation inhibitory activity was more effectively than those obtained using as standard antiglycation agent aminoguanidine. OM is a potent agent for protecting LDL against oxidation and glycation. Treatment of streptozotocin-diabetic mice with OM and glibenclamide for 28 days had beneficial effects on renal metabolic abnormalities including glucose level and AGEs formation. Diabetic mice showed increase in tail tendon collagen, glycated collagen linked fluorescence and reduction in pepsin digestion. Treatment with OM improved these parameters when compared to diabetic control and glibenclamide.

Evaluation of the antioxidant and anti-glication effects of the hexane extract from Piper auritum leaves in vitro and beneficial activity on oxidative stress and advanced glycation end-product-mediated renal injury in streptozotocin-treated diabetic rats.

The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS). Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, ß-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE) formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

Assessing the Ameliorative Effect of Selenium Cinnamomum verum, Origanum majorana, and Origanum vulgare Nanoparticles in Diabetic Zebrafish (Danio rerio).

Cinnamomum verum, Origanum majorana, and Origanum vulgare have been used in traditional medicine for a long time to treat diabetes because of their promising therapeutic effects. The combination of these plants (COO) was tested to improve their efficacy using selenium nanoparticles (Se-COO-NPs) and gum Arabic (GA) as stabilizers for sustained release. Phenolic compounds of plants were identified using liquid chromatography-mass spectrometry (LC-MS/MS). GA-Se-COO-NPs were characterized by spectroscopic and microscopic methods and evaluated in diabetic zebrafish. The ultraviolet spectrum was assessed to confirm the formation of plasmon resonance at 267 nm. The obtained particle size of selenium nanospheres was 65.76 nm. They were maintained in a stable form for 5 months at 4 °C. Transmission electron microscopy (TEM) images demonstrated the presence of individual spherical nanoparticles. Fourier transform infrared spectroscopy (FT-IR) showed the interaction between COO extract and selenium, exhibiting good entrapment efficiency (87%). The elemental analysis of COO extract and GA-COO-SeNPs confirmed that NPs were obtained. The zebrafish were exposed to a high glucose concentration for two weeks, and type 2 diabetes and oxidative stress responses were induced. In diabetic zebrafish, treatment with NPs showed antilipidemic and hypoglycemic effects, high survivability, and reduced levels of glucose, reactive oxygen species (ROS), and lipids in the blood. This group this had a higher survivorship rate than the diabetic control. The results demonstrated that GA-Se-COO-NPs have high antidiabetic potential, most likely because of the synergic effects of phenolic compounds and Se nanoparticles.

Optimization of ultrasonic-assisted extraction of polyphenols from the polyherbal formulation of Cinnamomum verum, Origanum majorana, and Origanum vulgare and their anti-diabetic capacity in zebrafish (Danio rerio).

The Cinnamomum verum (CV), Origanum majorana (CM), and Origanum vulgare (OV) have been used in traditional medicine in several regions of México for their anti-diabetic properties. In this study investigated the variables of ultrasound-assisted extraction for the polyphenolic compounds from the combination of these plants and explore their potential antidiabetic activities on glucose-induced-diabetic zebrafish. Determined the optimum conditions for ultrasonic-assisted extraction (UAE) to maximum recovery amounts of phenolic compounds from the extract of these plants. Polyphenols were detected in the extracts using HPLC-DAD-analysis. Extracts were evaluated on zebrafish exposed to high glucose concentration (110 mM) for two weeks. Results showed second-order polynomial mathematical models with a high coefficient of determination (R2 > 0.9564). Optimized extraction conditions for UAE from the combination of the 3 plants (COV) were as follows: 66.03%, ethanol, 28.87 min, and 21.51 mL/g for maximal flavonoids extraction. Used the same optimal extraction conditions for CV, CM, and OV. Results from LC-MS/MS indicated 9 polyphenolic compounds in CV, 12 in CM, and 6 in OV, the content of total polyphenols was 310.28, 90.42, and 126.74 mg GAE 100 g-1 dry weight, respectively. However, hyperglycemic fish showed an increase in cholesterol and triglyceride levels whereas extracts completely prevented these metabolic alterations. COV showed higher anti-diabetic ability than CV, CM, and OV, suggesting a synergistic effect between them. Our investigation developed a new herbal formulation of Cinnamomum verum; Origanum majorana; Origanum vulgare that has proven effective in animals with type 2 diabetes will form a new class of supplements to treat diabetic complications.

Diterpenoids from the freshwater green algae Rhizoclonium hieroglyphicum with antibacterial activity.

Three new isopimarane diterpenes 7ß-hydroxy-19α-methylmalonyloxy-isopimara-8(14),15-diene (1), 7ß-hydroxy-14-oxo-isopimara-8(9),15-dien-19oic acid (2), and 7ß-hydroxy-14-oxo-19α-methylmalonyloxy-isopimara-9(11),15-diene (3) in addition to the known compounds isopimaric acid (4), 7oxo-13-epi-pimara-14,15-dien-18oic acid (5), 7oxo-13-epi-pimara-8,15-dien-18oic acid (6), and 6ß-hydroxyisopimaric acid (7) were isolated from the hexane extract of Rhizoclonium hieroglyphicum. The structures of compounds 1-7 were established by 1D and 2D NMR techniques. The isolated diterpenoids were screened for antimicrobial activity against gram-positive and gram-negative bacteria and yeast strains.

Effect of flavonoids from Prosthechea michuacana on carbon tetrachloride induced acute hepatotoxicity in mice.

CONTEXT: Prosthechea michuacana W.E. Higgins (LaLlave & Lex) (Orchidaceae) is an orchid that has been used in traditional medicine for the treatment of inflammation, diabetes, wound, and liver disorders. Therefore, we thought it would be worthwhile to study the effect of this orchid on liver damage using mice as model. OBJECTIVE: The present study investigates the effect of flavonoids isolated from methanol extract of P. michuacana on carbon tetrachloride (CCl(4))-induced liver damage in mice. MATERIALS AND METHODS: The methanol extract was purified by repeated column chromatography, resulting in the identification of five metabolites whose hepatoprotective effects were evaluated by measuring aspartate transaminase, alanine transaminase, alkaline phosphatase, glutamate, total bilirubin level, lactate dehydrogenase, total serum protein, and lipid peroxidation (thiobarbituric acid reactive substances assay) in CCl(4)-induced hepatic injury in mice. RESULTS: From the bulbs of P. michuacana, four known flavonoids were isolated (scutellarein 6-methyl ether, dihydroquercetin, apigenin 7-O-glucoside, and apigenin-7-neohesperidoside), together with the new flavonol glycoside apigenin-6-O-ß-D-glucopyranosil-3-O-α-L-rhamnopyranoside. Their structures were characterized by 1D and 2D nuclear magnetic resonance experiments. Treatment with flavonoids significantly prevented the biochemical measurable changes induced by CCl(4) in the liver. Compounds 1, 4, and 5 were found to exhibit good hepatoprotective effect. These effects were comparable to that of the standard drug silymarin, a well-known hepatoprotective agent. DISCUSSION: These results demonstrate that flavonoids contained in the bulbs of P. michuacana contribute to the hepatoprotective activity attributed to the plant.

Rapid Model to Evaluate the Anti-Obesity Potential of a Combination of Syzygium aromaticum (Clove) and Cuminun cyminum (Cumin) on C57BL6/j Mice Fed High-Fat Diet.

Several studies have demonstrated that the phytochemical contents of plants are potential anti-obesity agents. In this study we examine the effect of using a combination of dry buttons from Syzygium aromaticum and seeds from Cuminum cyminum (CC) on C57BL6/J mice induced with obesity via high-fat-diet (HFD). The aim of this study is to demonstrate that the method proposed in the study reduced obesity significantly after several weeks of experimentation. The extract from both plants was extracted using ultrasound to enhance the extraction of phytochemicals. Optimum extraction conditions were obtained with ethanol as follows: 50:50 v/v water with an ultrasound power of 300 W, and ultrasonication time of 30 minutes. The simultaneous administration of the CC extract in HFD for 5 weeks led to the regulation of lipid profiles (cholesterol and triglycerides), reduction of food intake, weight gain, adipose tissue and liver weight. Findings obtained by this obese model indicate that CC extract can prevent obesity. Compared with the traditional 16 weeks method (8 weeks to get fat, and 8 weeks to lose weight), similar results were obtained in the present study obese model in less time of experimentation.

Evaluation of the Antidiabetic Potential of Extracts of Urtica dioica, Apium graveolens, and Zingiber officinale in Mice, Zebrafish, and Pancreatic ß-Cell.

Medicinal plants are commonly used in the treatment of diabetes, particularly as they contain flavonoids and phenolic compounds. The present study aims to investigate the activities of a polyherbal formulation made from Urtica dioica, Apium graveolens, and Zingiber officinale (UAZ) against streptozotocin-nicotinamide ((STZ-NA)-induced type 2 diabetes in CD1 mice, glucose-induced type 2 diabetes (T2DM) in zebrafish, and high glucose-induced damage in RINm5F pancreatic ß-cells. In fasting mice, plasma glucose, glycosylated hemoglobin (HbA1C), lipid hydroperoxides (LOOH), thiobarbituric acid reactive substances (TBARS), and lipid profiles were significantly increased, whereas insulin, enzymatic antioxidants, and carbohydrate metabolic enzymes were altered significantly in diabetic mice. Zebrafish had similar glucose levels, liver enzymes, and lipid profiles compared to mice. The study investigated the effects of the extract in enhancing cell viability, insulin secretion, and reducing lipid peroxidation and intracellular reactive oxygen species (ROS) levels in RINm5F cells damaged by high glucose. All the above biochemical parameters were enhanced in both mice and zebrafish treated; the combined extract UAZ normalized all the biochemical parameters. The medicinal plant extracts, used either separately or in combination, ameliorated the adverse effect of glucose on cell viability and functionality of beta-RINm5F cells.

Evaluation of the Antidiabetic and Antihyperlipidemic Activity of Spondias purpurea Seeds in a Diabetic Zebrafish Model.

Diabetes mellitus (DM) is a serious chronic degenerative disease characterized by high levels of glucose in the blood. It is associated with an absolute or relative deficiency in the production and/or action of insulin. Some of the complications associated with DM are heart disease, retinopathy, kidney disease, and neuropathy; therefore, new natural alternatives are being sought to control the disease. In this work, we evaluate the antidiabetic effect of Spondias purpurea seed methanol extract (CSM) in vitro and in a glucose-induced diabetic zebrafish model. CSM is capable of lowering blood glucose and cholesterol levels, as well as forming advanced glycation end-products, while not presenting toxic effects at the concentrations evaluated. These data show that CSM has a promising antidiabetic effect and may be useful in reducing some of the pathologies associated with diabetes mellitus.

Antihyperglycemic, antihyperlipidemic and antiglycation effects of Byrsonima crassifolia fruit and seed in normal and streptozotocin-induced diabetic rats.

The hypoglycemic effects of hexane, chloroform and methanol extracts from fruits and seeds of Byrsonima crassifolia were evaluated by oral administration to normoglycemic and streptozotocin-induced severe diabetic rats (SD). The anti-diabetic effect was examined by blood glucose, triglycerides, lipid peroxidation, total cholesterol levels in the serum, glycogen content of liver and skeletal muscles, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and oxidized glutathione (GSSG) levels. The most active extracts were obtained with hexane. Hexane and chloroform extracts from fruits and seeds of Byrsonima crassifolia increased the levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase (G6Pase) and the plasma insulin levels. They also decreased glucokinase (GK) and TBAR (thiobarbituric acid assay). In conclusion, Byrsonima crassifolia possesses significant antihyperglycemic properties after 4 h of a single oral dose. It can also improve hyperlipidemia and hyperinsulinemia in streptozotocin-induced diabetic rats. Both extracts exhibited significant inhibitory activity against AGEs (advanced glycation end products) formation with IC(50) values ranging from 94.3 to 138.7 µg/ml. Therefore, B. crassifolia can be considered as a potential safe anti-diabetic agent.

Glucopyranoside flavonoids isolated from leaves of Spinacia oleracea (spinach) inhibit the formation of advanced glycation end products (AGEs) and aldose reductase activity (RLAR).

BACKGROUND AND PURPOSE: The formation and accumulation of advanced glycation end products (AGEs) and rat lens aldose reductase (RLAR) generated in the glycation process play an outstanding role in the complications of diabetes. Owing to the adverse effects of AGEs on diabetic patients, the search for new anti-AGE agents from plants without side effects has had significant interest from the researchers in the last decades for the development of a therapy that improves diabetic complications. Spinach could reverse the formation of AGEs and RLAR. This study aimed to investigate the ability of 10 known glucopyranosides flavonoids isolated from Spinacia oleracea on the formation of AGEs and RLAR in vitro and in vivo experiments. MATERIALS AND METHODS: Methanol extract of leaves of spinach was subjected to bioassay-guided fractionation using to silica gel column chromatographic followed by gel filtration by Sephadex LH-20. BSA glucose system and in vitro bioassays using rat lens aldose reductase (RLAR) were employed to evaluated inhibitory activity on the formation of AGEs. The induced diabetes in zebrafish by immersing in a 111 mM glucose solution for 14 days, revealed increased glycation of proteins in the eyes. Measurements of glycated hemoglobin and fructosamine were used to verify the anti-AGEs effect of the isolated flavonoids. KEY RESULTS: Through bioassay-guided fractionation of methanol extract of leaves spinach, ten known glucopyranoside flavonoids (1-10) have been isolated, and spectroscopic studies established their structures. Among the isolated compounds are: patuletin-3-O-(2"-coumaroylglucosyl)-(1→6)-[apiosyl-(1→2)]- ß-d-glucopyranoside (7), patuletin 3-O-(2"-feruloyl glucosyl)-(1→6)-[apiosyl-(1→2)]- ß-d-glucopyranoside (8), they have shown potent inhibition on AGEs formation, stronger than the positive controls used in the different experiments. CONCLUSION AND IMPLICATIONS: The findings indicated that glucopyranoside flavonoids found in Spinacia oleracea might have therapeutic potential for decreasing protein glycation, and might ameliorate AGE-related diabetic complications.

Cucurbita argyrosperma Seed Extracts Attenuate Angiogenesis in a Corneal Chemical Burn Model.

Severe corneal inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. In this study, we used the cornea to examine the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, methanol (Met) and hexane (Hex), from the seed of Cucurbita argyrosperma, on inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. We evaluated: opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological changes. Also, we assessed the inflammatory (cyclooxigenase-2, nuclear factor-kappaB, and interleukin-1ß) and angiogenic (vascular endothelial growth factor A, VEGF-A; -receptor 1, VEGFR1; and -receptor 2, VEGFR2) markers. Levels of Cox-2, Il-1ß, and Vegf-a mRNA were also determined. After treatment, we observed a reduction in corneal edema, with lower opacity scores and cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased the CNV area. The staining of inflammatory and angiogenic factors was significantly decreased and related to a down-expression of Cox-2, Il-1ß, and Vegf. These results suggest that intake of C. argyrosperma seed has the potential to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.