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.

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.

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.

Protection of silver nanoparticles using Eysenhardtia polystachya in peroxide-induced pancreatic ß-Cell damage and their antidiabetic properties in zebrafish.

BACKGROUND: The aim was to explore the efficacy of extract of Eysenhardtia polystachya-loaded silver nanoparticles (EP/AgNPs) on pancreatic ß cells, INS-1 cells, and zebrafish as a valuable model for the study of diabetes mellitus. MATERIALS AND METHODS: EP/AgNPs were synthesized using methanol/water bark extract of E. polystachya and characterized using various physicochemical techniques. RESULTS: Immersion of adult zebrafish in 111 mM glucose solution resulted in a sustained hyperglycemic, hyperlipidemic state, and serum insulin levels decreased. The synthesized EP/AgNPs showed an absorption peak at 413 nm on ultraviolet-visible spectroscopy, revealing the surface plasmon resonance of the nanoparticles. Transmission electron microscopy indicated that most of the particles were spherical, with a diameter of 10-12 nm, a polydispersity index of 0.197, and a zeta potential of -32.25 mV, suggesting high stability of the nanoparticles. EP/AgNPs promote pancreatic ß-cell survival, insulin secretion, enhanced hyperglycemia, and hyperlipidemia in glucose-induced diabetic zebrafish. EP/AgNPs also showed protection of the pancreatic ß-cell line INS-1 against hydrogen peroxide-induced oxidative injury. CONCLUSION: The results indicate that EP/AgNPs have good antidiabetic activity and therefore could be used to prevent the development of diabetes.

Ursane derivatives isolated from leaves of Hylocereus undatus inhibit glycation at multiple stages / 中国天然药物

The present study was designed to evaluate the therapeutic potential of bioactive compounds from chloroform extract of the leaves of Hylocereus undatus in the formation of advanced glycation end products (AGEs) in vitro. Bioactivity-guided fractionation of chloroform extract from Hylocereus undatus afforded two novel 12-ursen-type triterpenes, 3β, 16α, 23-trihydroxy-urs-12- en-28-oic acid (1) and 3β, 6β, 19α, 22α-tetrahydroxy-urs-12-en-28-oic acid (2), as well as four known triterpenes 2α, 3β, 23-tetrahydroxy-urs-11-en-28-oic acid (3), 3β-acetoxy-28-hydroxyolean-12-ene (4), 3β, 16α-dihidroxyolean-12-ene (5) and 3β-acetoxy-olean-12-ene (6). Our results revealed that triterpenes 1-3 were able to inhibit the formation of AGEs in all tested assays. The data indicated that the triterpenes had inhibitory activity at the múltiple stages of glycation and that there might be a high potential for decreasing protein oxidation and protein glycation that can enhance glycative stress in diabetic complications.

Ursane derivatives isolated from leaves of Hylocereus undatus inhibit glycation at multiple stages / 中国天然药物

The present study was designed to evaluate the therapeutic potential of bioactive compounds from chloroform extract of the leaves of Hylocereus undatus in the formation of advanced glycation end products (AGEs) in vitro. Bioactivity-guided fractionation of chloroform extract from Hylocereus undatus afforded two novel 12-ursen-type triterpenes, 3β, 16α, 23-trihydroxy-urs-12- en-28-oic acid (1) and 3β, 6β, 19α, 22α-tetrahydroxy-urs-12-en-28-oic acid (2), as well as four known triterpenes 2α, 3β, 23-tetrahydroxy-urs-11-en-28-oic acid (3), 3β-acetoxy-28-hydroxyolean-12-ene (4), 3β, 16α-dihidroxyolean-12-ene (5) and 3β-acetoxy-olean-12-ene (6). Our results revealed that triterpenes 1-3 were able to inhibit the formation of AGEs in all tested assays. The data indicated that the triterpenes had inhibitory activity at the múltiple stages of glycation and that there might be a high potential for decreasing protein oxidation and protein glycation that can enhance glycative stress in diabetic complications.

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.

Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice.

Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

Antimicrobial activities of diterpene labdane from seeds of Byrsonima crassifolia / Actividad antimicrobial de diterpenos labdanos de la semilla de Byrsonima crassifolia

Two compounds from the hexane extract of seeds of Byrsonima crassifolia were isolated and their structures elucidated using extensive spectroscopic analyses. These compounds are derived from the new labdane diterpene Labda-17-(1) and the known antimicrobial Labda-8 (17)-(2). The present study was aimed to study the effect antimicrobial of novel diterpene 1 against bacterial pathogens showed a moderate activity with MIC values 18.79-70.12 ug/ml and a MBC ranging between 250-1000 ug/ml against all assayed microorganisms.

Se aislaron dos compuestos del extracto de hexano de semillas de Byrsonima crassifolia y sus estructuras se dilucidaron por medio de extensos análisis espectroscópicos. Estos compuestos derivados del labdano corresponden al nuevo diterpeno Labda-17- (1) y el conocido antimicrobiano Labda-8(17)-(2). En el presente estudio se estudió el efecto antimicrobiano del nuevo diterpeno 1 sobre algunas bacterias patógenas mostrando sobre de estas una actividad moderada, con valores de MIC de 18.79-70.12 ug/ml y un rango de MBC que oscila entre 250-1000 ug/ml frente a todos los microorganismos ensayados.

Hexane extract of the seeds of Byrsonima crassifolia accelerates wound healing in streptozotocin-induced diabetic rats.

OBJETIVE: To study the effect of seeds of Byrsonima crassifolia in diabetic wound healing. METHODS: Wound healing potential of hexane extract in the form of simple ointment for the treatment of dermal wounds was studied in streptozotocin-induced diabetic rats on excision wound, incision wound and dead space wound. Various parameters such as epithelization period, scar area, tensile strength, hydroxyproline, total protein, DNA, hexosamine, uronic acid, antioxidant enzymes including superoxide dismutase (SOD) and catalase activity (CAT) were used to evaluate the effect of B. crassifolia on wound healing. RESULTS: Hexane extract in form topical accelerates the wound healing process by decreasing the surface area of the wound with a significant increase in the rate of wound contraction and tensile strength; increase granulation tissue dry weight, hydroxyproline, total protein, DNA and SOD and CAT when compared with diabetic control. CONCLUSION: B. crassifolia was effective in promoting diabetic wound healing in rats through the processes of tissue regeneration.

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).

Inhibition of advanced glycation end products formation by stilbene and phenanthrene derivatives from Prosthechea michuacana in vitro and in vivo / Inhibición de la formación de subproductos en la glicosilación avanzada por derivados de estilbeno y fenantreno de Prosthechea michuacana, in vitro e in vivo

In our previous study, we isolated from chloroform extract of the bulbs of orchid P. michuacana, three antioxidant compounds: two stilbene alpha-alpha´-dihydro, 3´,5´,2-trimethoxy-3-hydroxy-4-acetyl-4´-isopentenyl stilbene, 5-[2-(3-hydroxy-5-methoxyphenyl)ethyl]-2-methoxyphenol (gigantol) and one phenanthrene 4,6,7-trihydroxy-2-methoxy-8-(methylbut-2-enylphenanthren-1-1´-4´,6´,7´-trihydroxy-2´-methoxy-8´-(methylbut-2´-enyl)-phenanthrene. Following the study, we investigated the ability of isolated compounds to inhibit advanced glycation in vitro. Bovine serum albumin was glycated in the presence of glucose or methylglyoxal. Amadori-rich protein was prepared by dialyzing lysozyme that had been glycated by ribose. We also evaluated renal function by checking formation of advanced glycation and tail tendon collagen quality in streptozotocin-induced diabetic mice. Also determined the effect on LDL and hemoglobin. Compounds can efficiently inhibit the formation of AGEs by trapping reactive methylglyoxal and showed potent anti-Amadorin activity. Also exhibited a significant inhibitory activity on the glycated hemoglobin (GHb and HbA1c). Compounds showed a protective renal effect and reduction in mice tail tendon collagen. Also the tested compounds are potent agents for protecting LDL against oxidation and glycation. We concluded that compounds from P. michuacana are potent antiglycation agents, which can be of great value in the prevention of diabetic glycation-associated-pathogenesis.

En un estudio anterior, aislamos del extracto clorofórmico de los bulbos de la orquídea Prosthechea michuacana, tres compuestos antioxidantes: los estilbenos alfa-alfa´-dihidro, 3´,5´,2-trimethoxi-3-hidroxi-4-acetil-4´-isopentenil-stilbeno, 5-[2-(3-hydroxy-5-methoxyphenyl)ethyl]-2-methoxyphenol (gigantol) y el fenantreno 4,6,7-trihidroxi -2-methoxi-8-(metilbut-2-enilfenantren-1-1´-4´,6´,7´-trihidroxi-2´-metoxi-8´-(metilbut-2´-enil)-fenantreno. Continuando con el estudio, investigamos la capacidad de estos compuestos para inhibir la glicación avanzada in vitro. La seroalbúmina bovina se glicosiló en presencia de glucosa o metilglioxal. La reacción de Amadori se determinó con lisozima glicosilada previamente tratada con ribosa. También se evaluó la función renal mediante la formación de la glicación avanzada y la inhibición de AGEs en el ensayo sobre el colágeno del tendón de la cola en ratones con diabetes inducida con estreptozotocina. También determinamos el efecto de los compuestos aislados sobre LDL y hemoglobin. Los compuestos pueden inhibir eficazmente la formación de AGE atrapando el metilglioxal reactivo y muestran potente actividad anti Amadorin. También mostraron una actividad inhibitoria significativa en la formación de la hemoglobina glucosilada, GHB y HbA1c. Mostraron un efecto protector renal y una reducción en el colágeno glicosiladó del tendón de la cola. También estos compuestos son potentes agentes para la protección de LDL frente la oxidación y la glicación. En base a los resultados obtenidos se concluye que los compuestos aislados son potentes agentes antiglicación, que pueden ser de gran valor en la prevención de la patogénesis de la diabetes asociada a la glicación.

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.

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.

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.