Pulse Proteins and Their Hydrolysates: A Comprehensive Review of Their Beneficial Effects on Metabolic Syndrome and the Gut Microbiome.

Pulses, as an important part of the human diet, can act as a source of high-quality plant proteins. Pulse proteins and their hydrolysates have shown promising results in alleviating metabolic syndrome and modulating the gut microbiome. Their bioactivities have become a focus of research, with many new findings added in recent studies. This paper comprehensively reviews the anti-hypertension, anti-hyperglycemia, anti-dyslipidemia and anti-obesity bioactivities of pulse proteins and their hydrolysates in recent in vitro and in vivo studies, which show great potential for the prevention and treatment of metabolic syndrome. In addition, pulse proteins and their hydrolysates can regulate the gut microbiome, which in turn can have a positive impact on the treatment of metabolic syndrome. Furthermore, the beneficial effects of some pulse proteins and their hydrolysates on metabolic syndrome have been supported by clinical studies. This review might provide a reference for the application of pulse proteins and their hydrolysates in functional foods or nutritional supplements for people with metabolic syndrome.

Antihyperlipidemic effect and GC-MS analysis of phytoconstituents from Laurus nobilis essential oil in rat.

This study aimed to evaluate the effect of Laurus nobilis (L. nobilis) essential oil (EOs) (80 mg/kg) on Triton WR-1339-induced dyslipidemia in Wistar rats. The effect of L. nobilis essential oil (80 mg/kg) on lipid and lipoprotein profile was examined on Triton WR-1339-induced dyslipidemia in rats. Furthermore, the phytochemical evaluation was performed by GC-MS. In Addition, the acute toxicity of this EO was evaluated at a dose of 2 g/kg. The results revealed that the main constituents of L. nobilis EO were 1,8-cineole (39.5%), linalool (13.09%), and a-terpineol (11.55%). Furthermore, the EO did not cause any signs of toxicity or mortality, and the acute lethal dose 50 (LD50) was estimated to be higher than 2 g/kg. L. nobilis EO ameliorated lipid parameters and atherogenic indices. In conclusion, the study demonstrates that L. nobilis essential oils possess antidyslipidemic activity in acute model of hyperlipidaemia.

Antidiabetic and Antidyslipidemic Effects of Artemisia mesatlantica, an Endemic Plant from Morocco.

AIMS: The study aimed to assess the antihyperglycemic and antidyslipidemic activities of Artemisia mesatlantica. BACKGROUND: Artemisia mesatlantica is an endemic plant of Morocco used in traditional medicine as an alternative treatment for diabetes. OBJECTIVE: The study was designed to examine the antihyperglycemic and antidyslipidemicability of aqueous extract of Artemisia mesatlantica (AMAE) in experimental animal models. METHODS: The effect of the single and repeated oral administration (7 days of treatment) of AMAE (60 mg/kg) on blood glucose and lipid profile were assessed in normal and streptozotocin-induced diabetic rats. Furthermore, to confirm the antidyslipidemic effect of Artemisia mesatlantica, a model of hyperlipidemia induced by tyloxapol (Triton WR-1339) in rats was used. RESULTS: The AMAE (60 mg/kg) was able to significantly reduce glycaemia, improve lipid profile and increase hepatic glycogen content in STZ-induced diabetic rats. In addition, pretreatment of rats for 7 consecutive days with an aqueous extract of Artemisia mesatlantica (600 mg/kg) prior to tyloxapol injection prevented increases in plasma levels of total cholesterol, triglycerides and LDL-c. CONCLUSION: From these observed results, it can be deduced that Artemisia mesatlantica possesses remarkable antidiabetic and antihyperlipidemic properties.

The significant antidyslipidemic, hypoglycemic, antihyperglycemic, and antiobesity activities of the aqueous extracts of Agave Sisalana juice are partly mediated via modulation of calcium signaling pathways.

Plant species in the genus Agave, including Agave sisalana, have found extensive application in African and Asian traditional medicine. Inspired by the use of the edible sweet sap known as Aguamiel (obtained from specific mature agave species such as Agave salmiana) in Mexico by diabetic patients to improve their diabetic condition, this study investigated the effects of Agave sisalana extracts prepared by lyophilization, fermentation, and saponin extraction from sisal juice in a rodent model of metabolic syndrome. The metabolic syndrome was induced by administering a high fat and high fructose diet to freshly weaned Sprague-Dawley rats for eight weeks. The A. sisalana extracts possessed significant hypoglycemic effects [3.883 ± 0.371 mmol/L (normal group) vs. 8.183 ± 0.5845 mmol/L (negative control) vs. 3.767 ± 0.2716 mmol/L (positive control) vs. 4.167 ± 0.4602 mmol/L (FSP) vs. 4.533 ± 0.3169 mmol/L (FerSP) vs. 3.5 ± 0.2309 mmol/L (FS LD) vs. 3.867 ± 0.3353 mmol/L (FS HD) vs. 4.617 ± 0.2725 mmol/L (FerS LD) vs. 4.383 ± 0.3114 mmol/L (FerS HD): p < 0.0001]. The extracts also possessed significant antihyperlipidemic effects with significant differences in total serum cholesterol between the groups [1.398 ± 0.1232 mmol/L (normal group) vs. 4.225 ± 0.4135 mmol/L (negative control) vs. 1.582 ± 0.154 mmol/L (positive control) vs. 1.245 ± 0.0911 mmol/L (FSP) vs. 1.393 ± 0.1423 mmol/L (FerSP) vs. 1.387 ± 0.0924 mmol/L (FS LD) vs. 1.761 ± 0.1495 mmol/L (FS HD) vs. 1.698 ± 0.1294 mmol/L (FerS LD) vs. 1.6975 ± 0.0982 mmol/L (FerS HD): p < 0.0001]. Further, significant antiobesity effects of the A.sisalana extracts were observed with significant differences in weight among the groups [196.3 ± 6.49 g (normal group) vs. 298.9 ± 6.67 g (negative control) vs. 215.3 ± 6.06 g (positive control) vs. 195.4 ± 3.92 g (FSP) vs. 213.1 ± 5.21 g (FerSP) vs. 190.8 ± 6.49 g (FS LD) vs. 198.9 ± 4.31 g (FS HD) vs. 204.7 ± 4.78 g (FerS LD) vs. 208.7 ± 6.21 g (FerS HD): p < 0.0001]. Network pharmacology studies indicated that the chemical components found in sisal juice primarily exert their effects by modulating the voltage-gated calcium channels CACNA1S, CACNA1D, and CACNA1C, in the beta cells of the islets of Langerhans.

Antidiabetic Activity of Hydromethanolic Extract of Crude Dorstenia barnimiana Root: Validation of In Vitro and In Vivo Antidiabetic and Antidyslipidemic Activity.

BACKGROUND: Despite modern therapeutic armamentaria, DM remains a 21st-century public health menace. Novel phytomedicines are a rapidly expanding focus of research. The juice of Dorstenia barnimiana roots has long been used for the treatment of diabetes mellitus in traditional Ethiopian medicine, but its efficacy has not been supported by in vitro or in vivo scientific study. To investigate this, the present work was performed. METHODS: In this experimental study, simple random sampling was applied. Healthy male mice were used in normoglycemic and oral glucose-tolerance test (OGTT) models. Streptozotocin (IP, 150 mg/kg)-administered diabetic male mice were utilized. Animals were randomly divided into five groups of six each. Group I received 10 mL/kg distilled water, groups II-IV received 100 (DB100), 200 (DB200), and 400 (DB400) mg/kg crude extract, respectively, and group V received glibenclamide 5 mg/kg. A sham group (group VI) was added that received 10 mL/kg distilled water. All treatments were given orally. FBG, serum-lipid profiles, and body-weight changes were then measured. In vitro α-amylase inhibitory activity was also evaluated. RESULTS: The doses were atoxic up to 2,000 mg/kg. There was α-amylase inhibition activity of 67.52% at 500 µg/mL with an IC50 of 4.595 µg/mL. The OGTT revealed an antihyperglycemic effect of the crude extract. This was not attributed to a hypoglycemic side effect. In the diabetic mouse model, it shrank FBG levels remarkably. There were also significant reductions in serum TC, TGs, VLDL-C, and LDL-C. Nevertheless, HDL-C and body-weight levels returned. CONCLUSION: The present study confirmed the safety and promising in vivo antidiabetic and antidyslipidemic activity of D. barnimiana, thus corroborating the traditional claim.

Antidyslipidemic Capacity of Cleome arabica (L.) in Streptozotocin-Induced Diabetic Rats.

AIMS: The aim of the study was to assess the effect of Cleome arabica on lipid metabolism. BACKGROUND: Cleome arabica (L.) is a medicinal plant used traditionally by the population of North Africa for managing diabetes mellitus. OBJECTIVE: This study was designed to evaluate the antidyslipidemic and antiatherogenic capacities of Cleome arabica (L.) in normal and streptozotocin(STZ)-induced diabetic rats. METHODS: The hypolipidemic, antihyperglycemic and antiatherogenic effects of oral administration of the aqueous extract of Cleome arabica (CAAE) (100 mg/kg) were evaluated in normal and diabetic rats. In addition, the quantification of polyphenols, flavonoids and tannins as well as the antioxidant activity were performed. RESULTS: The results showed that the extract (CAAE) revealed an antidyslipidemic action by attenuating plasma levels of Total Cholesterol (TC), Triglycerides (TGs), Low-Density Lipoprotein cholesterol (LDL-c), Very low-density lipoprotein cholesterol (VLDL-c) and glucose. Additionally, CAAE exhibited a potent antiatherogenic activity by reducing Atherogenic Coefficient (AC), Castelli's Risk index-I (cri-I), and Castelli's Risk Index-II (CRI-II). Furthermore, the findings indicated that CAAE is abundant with polyphenols, flavonoids and tannins, and exhibited an important antioxidant capacity. CONCLUSION: The study demonstrates that aqueous Cleome arabica extract was able to ameliorate lipid abnormalities associated with diabetes mellitus. This pharmacological activity might be due to the antioxidant capacities of phytochemical compounds.

Erectcyanthins A-C from marine sponge Hyrtios erectus: anti-dyslipidemic agents attenuate hydroxymethylglutaryl coenzyme A reductase.

Bioactivity-steered chromatographic purification of the solvent extract of marine sponge Hyrtios erectus (Thorectidae) led to the isolation of three undescribed cyanthiwigin-type diterpenoids, erectcyanthins A-C. Erectcyanthin B exhibited comparable attenuation activity against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (IC50 0.07 mM) with that displayed by anti-dyslipidemic agent atorvastatin (IC50 0.08 mM). Comparatively greater antioxidant properties of erectcyanthin B (IC50 ∼ 0.4 mM) than that displayed by erectcyanthin A (IC50 ∼ 0.5 mM), erectcyanthin C and the standard α-tocopherol (IC50 1.5-1.7 mM) against oxidants also corroborated its promising bioactivity. Erectcyanthin B exhibited considerably greater anti-inflammatory activities (IC50 0.88-1.09 mM) than other erectcyanthin analogues in the series. The potential anti-dyslipidemic activity of erectcyanthins was linearly correlated with electronic parameter (topological polar surface area ∼ 74.6) along with balanced hydrophilic-lipophilic properties (logarithmic octanol-water partition coefficient 1.76). This study recognized the anti-dyslipidemic property of erectcyanthin B as a promising pharmaceutical lead.

Coelogin ameliorates metabolic dyshomeostasis by regulating adipogenesis and enhancing energy expenditure in adipose tissue.

Obesity and associated metabolic disorders are heading up with an alarming rate in developing nations. One of highly sought solution for metabolic disorders is to identify natural molecule with an ability to reduce obesity and increase insulin sensitivity. Coelogin (CLN) is a phenanthrene derivative isolated from the ethanolic extract of Coelogyne cristata. In our constant efforts to identify novel anti-dyslipidemic and anti-adipogenic compounds using CFPMA (common feature pharmacophore model using known anti-adipogenic compounds) model, predicted possible anti-adipogenic activity of CLN. In vitro results showed significant inhibition of adipogenesis in 3T3-L1 and C3H10T1/2 cell by CLN. It arrests the cell cycle in G1 phase of interphase and inhibits mitotic clonal expansion to regulate adipogenesis. CLN elicits insulin sensitizing effect in mature adipocytes. During extracellular flux assessment studies, it increases oxidative respiration and energy expenditure in adipocytes. In vivo, CLN reversed HFD-induced dyslipidemia as well as insulin resistance in C57BL/6 mice. It promoted the expression of genes involved in improved mitochondrial function and fatty acid oxidation in eWAT. CLN restored energy expenditure and increased the capacity of energy utilization in HFD fed mice. Taken together, the study indicated beneficial effects of CLN in combating obesity-associated metabolic complications.

Plant/algal polysaccharides extracted by microwave: A review on hypoglycemic, hypolipidemic, prebiotic, and immune-stimulatory effect.

Microwave-assisted extraction (MAE) is an emerging technology to obtain polysaccharides with an extensive spectrum of biological characteristics. In this study, the hypoglycemic, hypolipidemic, prebiotic, and immunomodulatory (e.g., antiinflammatory, anticoagulant, and phagocytic) effects of algal- and plant-derived polysaccharides rich in glucose, galactose, and mannose using MAE were comprehensively discussed. The in vitro and in vivo results showed that these bioactive macromolecules with the low digestibility rate could effectively alleviate the fatty acid-induced lipotoxicity, acute hemolysis, and dyslipidemia status. The optimally extracted glucomannan- and glucogalactan-containing polysaccharides revealed significant antidiabetic effects through inhibiting α-amylase and α-glucosidase, improving dynamic insulin sensitivity and secretion, and promoting pancreatic ß-cell proliferation. These bioactive macromolecules as prebiotics not only improve the digestibility in gastrointestinal tract but also reduce the survival rate of pathogens and tumor cells by activating macrophages and producing pro-inflammatory biomarkers and cytokines. They can effectively prevent gastrointestinal disorders and microbial infections without any toxicity.

The effects of Rosmarinus officinalis L. essential oil and its nanoemulsion on dyslipidemic Wistar rats.

Dyslipidemias are lipid metabolism alterations that cause increased levels of serum lipoprotein, cholesterol, and triglycerides. These alterations are associated with a higher incidence of cardiovascular diseases and are a risk factor for atherosclerosis development. This study aimed to evaluate the effect of Rosmarinus officinalis essential oil (EORO, 100 mg/kg) and its nanoemulsion (NEORO, 500 µg/kg) on Triton and coconut saturated-fat-induced (CSF) dyslipidemias using Wistar rats. The phytochemical evaluation of EORO performed by gas chromatography-mass spectroscopy (GC-MS) revealed 1,8-cineole (33.70%), camphor (27.68%), limonene (21.99%), and α-pinene (8.13%) as its major compounds. Triton-induced dyslipidemia significantly increased total cholesterol, LDL, and triglycerides levels. On the other hand, the groups treated with EORO and NEORO had significantly reduced total cholesterol, LDL, and triglycerides compared to the group treated only with Triton. Similar results were observed on the positive control treated with simvastatin. Dyslipidemia induced with coconut saturated-fat (CSF) caused abdominal fat gain, hypercholesterolemia, hypertriglyceridemia, increased LDL levels, and atherogenesis in the aorta. In contrast, the groups treated with EORO, NEORO, and simvastatin had significantly reduced hypercholesterolemia and hypertriglyceridemia, reduced abdominal fat gain, and absence of atherogenesis in the vascular endothelium. Overall, in the Triton-induced dyslipidemia model, EORO treatment had superior values than NEORO's (and simvastatin), although the differences were not too high, while in the CSF model, the values were mixed. In this manner, our results show an anti-dyslipidemic and anti-atherogenic activity effect by EORO and NEORO.

Evaluation of in vivo antidiabetic, antidyslipidemic, and in vitro antioxidant activities of hydromethanolic root extract of Datura stramonium L. (Solanaceae).

BACKGROUND: The global morbidity and mortality rates of diabetes mellitus are persistently increasing. There is a demand for new antidiabetic drugs because the safety and efficacy of currently available medications are limited. The present study was therefore conducted to study the antidiabetic activities of the hydromethanolic root extract of Datura stramonium L. (Solanaceae) in mice. METHODS: Blood glucose lowering activity of three doses (100, 200, and 400 mg/kg) of the hydromethanolic root extract of D. stramonium was tested on normoglycemic, oral glucose-loaded, and streptozotocin (STZ)-induced diabetic mice models. The effect of the extract on body weight and diabetic dyslipidemia was also studied on STZ-induced diabetic mice. Additionally, antioxidant activity of the plant extract was determined using 2,2-diphenyl-1-picrylhydrazine free radical scavenging assay. Data were analyzed using one way ANOVA followed by Tukey's post hoc multiple comparison test. RESULTS: The hydromethanolic root extract did not show significant hypoglycemic activity in normoglycemic mice. The plant extract at doses of 100, 200, and 400 mg/kg significantly (P<0.05) reduced blood glucose levels of oral glucose-loaded and diabetic mice. All the three doses of the root extract significantly improved diabetic dyslipidemia and the body weight of diabetic mice. Free radical scavenging activity of the root extract was found to be comparable to ascorbic acid with an IC50 of 13.47 µg/mL. CONCLUSION: This study demonstrated that the hydromethanolic root extract of D. stramonium possesses significant antidiabetic, antidyslipidemic, and antioxidant activities.

Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Antioxidant and Anti-hyperglycemic Activity.

A series of substituted oxopropanylindole hydrazone derivatives was synthesized and evaluated for anti-oxidant and anti-dyslipidemic activity. Of the 12 tested, 3 compounds (6c, 7b and 7d) showed good anti-oxidant activity, compound 6c attenuated LDL oxidation by 32%. The compounds 6c and 7d also showed good anti-dyslipidemic activity by reducing serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). These two compounds were further evaluated for antiadipogenic and anti-hyperglycemic activity, where 6c showed 44% reduction in lipid accumulation and 20.5% and 24.3% reduction in blood glucose at 5h and 24h respectively, as compared to standard drug metformin. Thus, compounds 6c and 7d with balanced anti-oxidant and anti-dyslipidimic activities may be excellent candidates for lead optimization and drug development for the treatment of metabolic disorders.

Pharmacological evaluation of the efficacy of Dysoxylum binectariferum stem bark and its active constituent rohitukine in regulation of dyslipidemia in rats.

The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum stem bark and its major active constituent rohitukine was evaluated in a high fat diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200 mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay guided fractionation of ethanolic extract resulted in the identification of known alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg) significantly decreased the plasma levels of total cholesterol (24 %), phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %) and low density lipoprotein (32 %) accompanied with an increase in high density lipoprotein (21 %). The present study demonstrated that ethanolic extract of Dysoxylum binectariferum stem bark and its major constituent rohitukine both have antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity of rohitukine can be correlated to its effect on enzymes involved in lipid metabolism.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1ß and TNF-α were diminished after 10 days' treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Experimental Validation of Antidiabetic and Antioxidant Potential of Cassia tora (L.): An Indigenous Medicinal Plant.

The present study was undertaken to evaluate antidiabetic and antioxidant activities of Cassia tora (C. tora) seeds extract against streptozotocin induced diabetes in experimental rats to scientifically validate its use against diabetes. Ethanolic extract of C. tora seeds extract and standard drug (glibenclamide) prepared in aqueous gum acacia (2 %, w/v) suspension and fed orally to streptozotocin induced male adult diabetic rats of Charles Foster strain for 15 days. Biochemical parameters in normal, diabetic control, standard (600 µg/kg bw p.o.) and treated (500 mg/kg bw p.o.) animal groups were quantified and compared. Treatment of streptozotocin induced diabetic rats with ethanolic seeds extract caused significant (p < 0.001) reduction in blood glucose (270-220 mg/dl), total cholesterol (140-104 mg/dl), triglyceride (149-99 mg/dl), phospholipids (100-74 mg/dl), free fatty acid (2.39-2.00 µmol/l), lipid peroxide (9-5.63 nmol MDA/dl) and significantly increased post heparin lipolytic activity (11-14 nmol FFA released/h/l plasma) (p < 0.001). Furthermore, the seeds extract (100-400 µg) when tested for its antioxidant activity in vitro, showed significant (p < 0.001) inhibition in the generation of super oxide anions in enzymic system a (46-37, 33, 23, 21 nmol uric acid formed/min), in enzymic system b (113-91, 77, 60, 51 nmol formazon formed/min), non-enzymic system (324-230, 211, 161, 141 nmol uric acid formed/min) and hydroxyl radicals in enzymic system (544-501, 411, 319, 291 nmol 2,3-dihydroxybenzoate formed/h) and non-enzymic system (28-21, 17, 14, 12). The results of the present study demonstrated antidiabetic, antidyslipidemic and antioxidant activities of C. tora seeds which could help in prevention of diabeticdyslipidemia and related complications.

Pharmacological evaluation of aqueous extract of syzigium cumini for its antihyperglycemic and antidyslipidemic properties in diabetic rats fed a high cholesterol diet-Role of PPARγ and PPARα.

In India syzygium cumini (Myrtaceae) is commonly used traditional medicine to treat diabetes. The present study was undertaken to assess an investigation of antihyperglycemic and antidyslipidemic properties of aqueous extract of Syzigium Cumini (SC) in diabetic rats fed a high cholesterol diet. The aqueous extract of SC was screened for antihyperglycemic and antidyslipidemic activity by streptozotocin induced diabetes in rats. Animals were treated with 100, 200 and 400mg/kg body weight of aqueous extract of SC. Metformin were used as reference antihyperglycemic drugs for comparison. Administration of aqueous extract of SC or metformin for 21days resulted in a significant (P<0.05) reduction in serum glucose, insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) compared with diabetic controls. Treatment with 100mg/kg/day aqueous extract of SC did not result in a significant reduction in serum insulin levels, but 200mg/kg/day and 400mg/kg/day, aqueous extract of SC and metformin showed significant reductions 17.89%, 19.60% and 24.40%, respectively. Furthermore, administration of 100, 200 and 400mg/kg/day, aqueous extract of SC and metformin resulted in significant decrease in insulin resistance of 19.20%, 41.59%, 51.55% and 68.68%, respectively. In high fat diet- streptozotocin (HFD - STZ) treated rats ß-cells function (HOMA-B) were markedly reduced (5.8-fold), however observed a significant (P<0.01) improvement of ß-cell function with aqueous extract of SC (400mg/kg/day) and metformin. The aqueous extract of SC seeds exhibits significant insulin-sensitizing, antidyslipidemic, antioxidant, anti-inflammatory and ß-cell salvaging activity in HFD-STZ-induced type 2 diabetic rats via overexpression of PPARγ and PPARα activity, affirming its potential to be used in the prevention and treatment of type 2 diabetes mellitus (T2DM). Further isolation and characterization of active components in SC seed extract are needed to explore the other possible mechanisms and pathways that are involved in its anti-diabetic effect.

Antidiabetic, antidyslipidemic and toxicity profile of ENV-2: A potent pyrazole derivative against diabetes and related diseases.

Diabetes is a major health problem and a predisposition factor for further degenerative complications and, therefore, novel therapies are urgently needed. Currently, cannabinoid receptor 1 (CB1 receptor) antagonists have been considered as promissory entities for metabolic disorders treatment. Accordingly, the purpose of this work was the evaluation of the sub-acute antidiabetic, anti-hyperglycemic, antidyslipidemic and toxicological profile of ENV-2, a potent hypoglycemic and antioxidant CB1 receptor antagonist. In this study, ENV-2 showed a pronounced anti-hyperglycemic effect even at a dose of 5mg/kg (P<0.05) in a glucose tolerance test on normoglycemic rats. Moreover, after administration of ENV-2 (16mg/kg) to diabetic rats, a prominent antidiabetic activity was observed (P<0.05), which was higher than glibenclamide. Sub-acute treatment (10 days) of ENV-2 resulted in a significant reduction of plasma glucose (P<0.05). Also, the levels of peripheral lipids were improved; blood triacylglycerols (TG) and cholesterol (CHOL) were diminished (P<0.05). In addition, it was found that ENV-2 reduced IL-1ß and IL-18 mRNA expression in adipose tissue (P<0.05). Due to the satisfactory outcomes, we were interested in evaluating the toxicity of ENV-2 in both acute and sub-chronic approaches. Regarding the acute administration, the compound resulted to be non-toxic and was grouped in category 5 according to OECD. It was also found that sub-chronic administration did not increase the size of the studied organs, while no structural damage was observed in heart, lung, liver and kidney tissues. Finally, neither AST nor ALT damage hepatic markers were augmented.

Antidiabetic Potential of Potentilla fulgens Roots in Validated Animal Models of Diabetes

The present study was undertaken to investigate the antidiabetic potential of tap roots of Potentilla fulgens in streptozotocin induced diabetic rat models. The crude powder, ethanolic, ethanolic: aqueous and aqueous extracts of tap roots were administered to normoglycemic- and streptozotocin (STZ)-induced diabetic rats in a single dose study. The ethanolic extract showed significant improvement in oral glucose tolerance and antihyperglycemic effect on sucrose loaded normal rats and STZ-induced diabetic rats. Of the isolated aqueous, n-butanol, chloroform and n-hexane soluble fractions of the active ethanolic extract of the roots, the aqueous fraction (100 mg/kg body weight) showed significant blood glucose lowering effect on STZ-induced diabetic rats. In a multiple dose study, aqueous fraction of ethanolic extract of P. fulgens roots significantly improved the body weight, percent glycated hemoglobin (%HbA1c), fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, lipid profile, liver and kidney parameters in STZ-induced diabetic rats. The aqueous fraction also showed marked improvement in OGTT and serum insulin level in neonatal STZ-induced diabetic rats for 30 consecutive days. The aqueous fraction of the roots also inhibited the activity of alpha (α)-glucosidase enzyme in a dose dependent manner. In conclusion, the finding suggested that an aqueous fraction of tap roots of P. fulgens possessed potential antidiabetic activity.

Assay method for quality control and stability studies of a new anti-diabetic and anti-dyslipidemic flavone (S002-853).

BACKGROUND: Flavonoid-rich extract of the plant is long known for its anti-diabetic activities in traditional medicine. S002-853, a new flavone derivative synthesized by Central Drug Research Institute (CDRI) has been used for the present study. OBJECTIVES: The present study aimed at development of an assay method for quality control (QC) and stability studies of a new anti-diabetic and anti-dyslipidemic agent CDRI compound S002-853. MATERIALS AND METHODS: A validated high-performance liquid chromatography analysis method for S002-853 was developed for in process QC and stability studies. The separation was achieved on a RP-C18 (25 cm × 0.4 cm, 5 µm, Phenomenex) at 240 nm with flow rate of 1.0 ml/min. This method was applied successfully in establishing forced degradation and drug-excipient testing protocols as per International Conference on Harmonization guidelines. RESULTS: The result of estimation and stress testing studies indicated a high degree of selectivity of this method. S002-853 was most stable at pH 7 and under photolytic conditions. The temperature degradation pattern of S002-853 was found to follow the zero order degradation. CONCLUSION: The method described is easy and simple hence can be easily reproduced. This method can be very useful for bulk manufacture QC, and drug development process.

Review of the Safety and Efficacy of Moringa oleifera.

Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti-hyperglycemic (antidiabetic) and anti-dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable.