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OBJECTIVE The effect of Alstonia boonei fractions on glucose homeostasis was investigated via in vitro enzyme inhibition activity, ex vivo glucose uptake assay, and in vivo methods in diabetic rats. METHODOLOGY A. boonei fractions were subjected to in vitro α-glucosidase inhibitory assay and then ex vivo glucose uptake activity. The butanol fraction of the leaves (ABBF) was picked for the in vivo assay since it showed more activity in the initial tests conducted. ABBF was administrated via oral dosing to six-weeks old fructose-fed STZ-induced type 2 diabetic rats over a 5-week experimental period. RESULTS ABBF treatment at a low dose of 150 mg/kg bw, significantly (p

The plants fractions of Caralluma adscendens var. gracilis and Caralluma pauciflora were evaluated for their total phenolic content in relation to their antioxidant activity and inhibitory effect of starch and lipids digestive enzymes. Among all fractions of C. adscendens var. gracilis and C. pauciflora, diethyl ether fractions showed highest phenolic content (36.23 ± 1.51 mg of GAE g− 1 DW, 28.21 ± 3.61 mg of GAE g− 1 DW), DPPH radical scavenging activity (27.96 ± 3.45 µg ml− 1 and 37.23 ± 0.92 µg ml− 1), inhibition of α-glucosidase (59.13 ± 1.31 µg ml− 1 and 73.03 ± 2.04 µg ml− 1), α-amylase (78.1 ± 3.47 µg ml− 1 110.5 ± 4.1µg ml− 1) and pancreatic lipase (41.91 ± 3.51 µg ml− 1 and 49.12 ± 3.89 µg ml− 1) compared to butanone and n-butanol fractions which showed little or no significant activities compared to standards. To the best of our knowledge, the present study provides the first evidence that these two plants (C. adscendens var. gracilis and C. pauciflora) are potent inhibitors of key enzymes in type 2 diabetes and obesity studies in vitro.

Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P P P P P CCL2 (P TNF-alpha (P IL1B trended higher (P P P

The effect ofABBF treatment at a low dose of 150 mg/kg bw, significantly (These results suggest that ABBF could be exploited as a therapeutic potential for treating T2D.

Fatty liver is an abnormal metabolic condition of excess intrahepatic fat. This condition, referred to as hepatic steatosis, is tightly associated with chronic liver disease and systemic metabolic morbidity. The most prevalent form in humans, i.e. non-alcoholic fatty liver, generally develops due to overnutrition and sedentary lifestyle, and has as yet no approved drug therapy. Previously, we have developed a relevant large-animal model in which overnourished sheep raised on a high-calorie carbohydrate-rich diet develop hyperglycemia, hyperinsulinemia, insulin resistance, and hepatic steatosis. Here, we tested the hypothesis that treatment with thiamine (vitamin B1) can counter the development of hepatic steatosis driven by overnutrition. Remarkably, the thiamine-treated animals presented with completely normal levels of intrahepatic fat, despite consuming the same amount of liver-fattening diet. Thiamine treatment also decreased hyperglycemia and increased the glycogen content of the liver, but it did not improve insulin sensitivity, suggesting that steatosis can be addressed independently of targeting insulin resistance. Thiamine increased the catalytic capacity for hepatic oxidation of carbohydrates and fatty acids. However, at gene-expression levels, more-pronounced effects were observed on lipid-droplet formation and lipidation of very-low-density lipoprotein, suggesting that thiamine affects lipid metabolism not only through its known classic coenzyme roles. This discovery of the potent anti-steatotic effect of thiamine may prove clinically useful in managing fatty liver-related disorders. This article has an associated First Person interview with the joint first authors of the paper., Editor's choice: Experiments using overnourished sheep raised on a high-calorie liver-fattening diet, treated with and without thiamine, revealed that vitamin B1 protects against the development of fatty liver driven by overnutrition.

Fatty liver represents a significant metabolic pathology of excess intrahepatic fat in domestic animals and humans. Quantification of hepatic-fat content is therefore essential for diagnosis and investigation of liver and metabolic disease. However, the reproducibility of hepatic steatosis analysis is often low due to subjective and technical factors. We hypothesized that improvement in tissue-lipids extraction efficiency would contribute to the accuracy and precision of liver-fat determination. To test it, we investigated the effect of standardized tissue sonication on liver-fat quantification by the Folch method in sheep. Liver samples from grownup lambs of lean (n = 16) and fatty (n = 15) livers, and from pregnant ewes (n = 6) who died from pregnancy toxemia (PT), were used for hepatic-fat content determination with or without tissue sonication. In the grown lambs, an average hepatic-fat content of 6.6% was determined in sonicated compared to 5.1% in non-sonicated specimens (P = 0.0002). Similarly, in ewes with PT, an average of 12.5% was determined with sonication compared to 10.8% without it (P = 0.0006), and the reproducibility was higher with sonication (CV of 3.1 vs. 6.1%, respectively). Thus, tissue sonication improved the efficiency of liver-lipids extraction and was significant to the accuracy and precision of hepatic-fat determination. Enzymatic quantification of triglycerides was moderately correlated with the results obtained gravimetrically (r = 0.632, P < 0.005). The reported data provide reliable reference values for pregnancy toxemic sheep. The significant improvement in liver-fat quantification observed with the reported revised protocol is likely applicable to most mammals and humans.

A novel protocol for the rapid assembly of a hybrid framework based on amino acid, thiazolidine and quinoxaline scaffolds has been demonstrated by microwave irradiation. The quinoxalines with amino acid side chains 5a–5c were prepared in three steps from 2,4-dinitrofluorobenzene and the amino acids, valine, methionine, and tyrosine and subsequently reacted with four different aldehydes and thioglycolic acid to produce thiazolidine–quinoxaline hybrids with amino acid side chains 6a–6l. All synthesized compounds were evaluated for their in vitro antimicrobial, antioxidant, and antidiabetic activities. Compounds 6f, 6j, and 6k showed broad spectrum antimicrobial activity against Gram +ve and Gram –ve bacteria, whilst 6h, 6k, and 6l showed the best antioxidant activity in the same order of magnitude to that of ascorbic acid. Four of the compounds, 5c, 6d, 6g, and 6k showed activity against α-glucosidase and α-amylase similar to acarbose. Those compounds showing antibacterial activity possessed 4-fluorophenyl and 4-methoxyphenyl groups along with methionine and tyrosine side chains while the compounds showing antioxidant, α-glucosidase, and α-amylase activity contained 4-nitrophenyl and 4-methoxyphenyl groups on the thiazolidine moiety with mainly methionine and tyrosine side chains. The α-glucosidase and α-amylase inhibitory compound 5c did not have a thiazolidine moiety and 6d was the only active compound with a valine amino acid side chain. Compound 6k with a tyrosine side chain and a 4-methoxyphenylthiazolidine moiety on the quinoxaline scaffold showed good bioactivity in all three assays.

As a precursor for a universal metabolic coenzyme, vitamin B1, also known as thiamine, is a vital nutrient in all living organisms. We previously found that high-dose thiamine therapy prevents overnutrition-induced hepatic steatosis in sheep by enhancing oxidative catabolism. Based on this capacity, we hypothesized that thiamine might also reduce whole-body fat and weight. To test it, we investigated the effects of high-dose thiamine treatment in sheep under overnutrition and calorie-restricted undernutrition to respectively induce positive energy balance (PEB) and negative energy balance (NEB). Eighteen mature ewes were randomly assigned to three treatment groups (n = 6 each). The control group (CG) was administered daily with subcutaneous saline, whereas the T5 and T10 groups were administered daily with equivoque of saline containing 5 mg/kg and 10 mg/kg of thiamine, respectively. Bodyweight and blood biochemistry were measured twice a week for a period of 22 days under PEB and for a consecutive 30 days under NEB. Surprisingly, despite the strong effect of thiamine on liver fat, no effect on body weight or blood glucose was detectable. Thiamine did, however, increase plasma concentration of non-esterified fatty acids (NEFA) during NEB (575.5 ± 26.7, 657.6 ± 29.9 and 704.9 ± 26.1 µEqL−1 for CG, T5, and T10, respectively: p &lt, 0.05), thereby favoring utilization of fatty acids versus carbohydrates as a source of energy. Thiamine increased serum creatinine concentrations (p &lt, 0.05), which paralleled a trending increase in urea (p = 0.09). This may indicate an increase in muscle metabolism by thiamine. Reduction of fat content by thiamine appears more specific to the liver than to adipose tissue. Additional studies are needed to evaluate the potential implications of high-dose vitamin B1 therapy in muscle metabolism.

Cardiovascular diseases (CVDs) are becoming the major cause of deaths worldwide, and their treatment demands novel therapeutic strategies. In this connection, we have identified p21 activated kinase 1 (PAK1) as a novel therapeutic target for the treatment of myocardial infarction (MI), where its expression is decreased when MI is induced with isoproterenol (ISO), which was brought back normal with pretreatment of Vitex negundo leaf ethanolic extract (VNE). These results were also supported by histopathological studies, cardiac markers, antioxidants, and inflammatory cytokines (NF-κB and IL-1β). Further studies with GC-MS analysis of VNE and in silico experiments confirmed 5,7-dihydroxy-6,4',-dimethoxy flavonone and 3',5-dihydroxy-6,7,4',-trimethoxyflavone are responsible for either maintaining or inducing the expression of PAK1 to protect from MI. Our findings for the first time revealed the use of phytoconstituents in the treatment of MI.

The leaves of Dacryodes edulis were investigated for their anti-oxidative and anti-diabetic potentials in vitro. Extracts from sequential extraction with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and aqueous) of the leaves were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols respectively. Their inhibitory effects were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phospatase activities. Their antioxidant and anti-apoptotic effects on Fe2+ - induced oxidative injuries in pancreatic and hepatic tissues were also investigated ex vivo. The ethanol extract was subjected to Gas chromatography mass spectroscopy (GC-MS) and Fourier transform infrared (FTIR) spectroscopic analysis to identify its bioactive chemical constituents. The extracts showed potent free radical scavenging activity and significantly (p

Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3). Experiment 1 examined the effects of increasing concentrations (2.5–20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals. Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals. Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

Objective: To evaluate the efficacy of methanolic extract of Murraya koenigii (MMK) leaves in attenuating the hepatic damage inflicted by carbon tetrachloride (CCl4), a potent oxidative stress inducer and a model hepatotoxicant. Methods: Rats were divided into six groups of five each: normal control group, CCl4 group, CCl 4+silymarin group, CCl4+MMK group (200 mg/kg body weight), CCl4+MMK group (300 mg/kg body weight) and CCl4+MMK group (500 mg/kg body weight). Rats were intraperitoneally injected with 20% CCl4 in corn oil (1 mL/kg body weight) and MMK was orally administered for 3 weeks. Levels of hepatic markers such as alanine transaminase, aspartate transaminase, alkaline phosphatase and total bilirubin were measured. Activities of superoxide dismutase, catalase and glutathione peroxidase were assayed and malondialdehyde content was measured. For histopathological examination, liver microtome sections were prepared and observed under light microscope. Results: Oral administration of MMK had significantly reduced the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin content in a dosedependent manner, which were elevated by CCl 4. However, CCl 4-induced rise in lipid peroxidation and drop in superoxide dismutase, catalase and glutathione peroxidase activities were reversed by MMK administration. Further, the hepatoprotective activity of MMK was supported by histopathological examination of liver microtome sections. Conclusions: Our biochemical and histological studies demonstrate the potential antioxidant and hepatoprotective activity of MMK and our results scientifically validate the often use of MMK leaves in food preparation and in Ayurvedic medicine in India and neighboring countries.

Human mortality has been significantly increased in last few decades due to the increased prevalence of obesity and associated chronic disorders such as type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease and atherosclerosis. Apart from genetic and medicine or drug related side effects, nearly 90-95% people became obese due to the imbalanced calorie intake and lack of nutritional knowledge. The anti-obesogenic drugs, Orlistat and Sibutramine, which have been duly approved by Food and Drug Administration (FDA), USA, work very well on diet-induced obesity however they are not getting popular to the people with overweight/obesity due to the higher cost and severe side effects. In contrast, plant based drugs have been considered as a better alternative due to their lower cost and negligible side effects. A number of medicinal plants and their bioactive constituents have received attention from scientists not only for their anti-obesity activity in vitro and in vivo but also in clinical trials. However, there is no systematic review of data available in the scientific domain in order to guide researchers to conduct further in depth research. In our present review, we differentiated the anti-obesogenic effects of various medicinal plant extracts, fractions and their bioactive compounds at in vitro, in vivo and clinical conditions. During our review, we could also identify the most effective plants with strong anti-obesogenic effects at in vitro or in vivo studies with lack of clinical trials when no one tried to isolate pure bioactive compounds from these plants. Hence, scientific community, government agencies/pharmaceutical industries should work together not only to isolate pure bioactive compounds but also to conduct clinical trials including toxicity to develop better alternative anti-obesity drugs.

The present study aimed to investigate the effects of the various parts of Ficus carica L. (figs) on antioxidant, antidiabetic, and antiobesogenic effects in vitro. Fruit, leaves, and stembark of the F. carica plant were sequentially extracted using organic and inorganic solvents and their total polyphenol and flavonoid contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes), and antiobesogenic (antilipase) activities were measured using several experimental models. The fruit ethanolic extract contained a high quantity of polyphenols and flavonoids (104.67±5.51 μg/mL and 81.67±4.00 μg/mL) compared with all other extracts. The activity of the ethanolic extract of F. carica fruit was significantly (p

Objective To evaluate the insecticidal, antimicrobial and antioxidant activities of bulb extracts of Allium sativum (A. sativum) . Methods Dried bulbs of A. sativum were extracted with different solvents and evaluated for insecticidal, antimicrobial and antioxidant activities. Methods Aqueous and methanol extracts showed highest insecticidal activity (mortality rate of 81% and 64% respectively) against the larvae of Spodoptera litura (S. litura) at a concentration of 1 000 ppm. With regard to antimicrobial activity, aqueous extract exhibited antibacterial activity against gram positive ( Bacillus subtilis, Staphylococcus aureu ,) and gram negative ( Escherichia coli and Klebsiella pneumonia ) strains and antifungal activity against Candida albicans . While methanol extract showed antimicrobial activity against all the tested micro organisms except two ( Staphylococcus aureus and Candida albicans ), the extracts of hexane, chloroform and ethyl acetate did not show any anti microbial activity. Minimum inhibitory concentration of aqueous and methanol extracts against tested bacterial and fungal strains was 100–150 μg/mL. Antioxidant activity of the bulb extracts was evaluated in terms of inhibition of free radicals by 2, 2′-diphenly-1-picrylhydrazyl. Aqueous and methanol extracts exhibited strong antioxidant activity (80%–90% of the standard). Conclusions Antioxidant and antimicrobial activity of A. sativum against the tested organisms therefore, provides scientific basis for its utilization in traditional and folk medicine. Also, our results demonstrated the insecticidal efficacy of A. sativum against S. litura , a polyphagous insect.

The prevalence and severity of obesity has increased markedly in recent decades making it a global public health concern. Since obesity is a potential risk factor in the development of hypertension, type-2 diabetes, cardiovascular diseases, infertility, etc., it is no more viewed as a cosmetic issue. Currently, only a few FDA-approved anti-obesity drugs like Orlistat, Lorcaserin and Phentermine-topiramate are available in the market, but they have considerable side effects. On the other hand, bariatric surgery as an alternative is associated with high risk and expensive. In view of these there is a growing trend towards natural product-based drug intervention as one of the crucial strategies for management of obesity and related ailments. In Asian traditional medicine and Ayurvedic literature a good number of plant species have been used and quoted for possible lipid-lowering and anti-obesity effects; however, many of them have not been evaluated rigorously for a definite recommendation and also lack adequate scientific validation. This review explores and updates on various plant species, their used parts, bioactive components and focuses multiple targets/pathways to contain obesity which may pave the way to develop novel and effective drugs. We also summarised different drugs in use to treat obesity and their current status. Nature is future promise of our wellbeing.

Aim The present study was aimed to investigate the role of Ficus carica L. (fig) aerial parts on antioxidant, antidiabetic and anti-obesogenic effects in vitro. Methods Fruit, leaves and stembark of Ficus carica plant were sequentially extracted by using organic and inorganic solvents and their total polyphenolics and flavonoids contents were estimated. The effects of the extracts on antioxidative, antidiabetic (inhibition of α-amylase and α-glucosidase enzymes) and anti-obesogenic (anti-lipase) activities were measured by using several experimental models. Results The fruit ethanolic extract contained a high amount of polyphenols and flavonoids (104.67±5.51μg·mL −1 and 81.67±4.00μg·mL −1 ). The ethanolic extract of Ficus carica fruit was significantly ( P −1 ), α-glucosidase (255.57±36.46μg·mL −1 ) α-amylase (315.89±3.83μg·mL −1 ) and pancreatic lipase (230.475±9.65μg·mL −1 ) assays indicate that fruit extracts were more active than other parts of the plant. The GC-MS analysis of the fruit extract shown the presence of sugars and polyphenolic compounds such as butyl butyrate, 5-hydroxy-methyl furfural, 1-butoxy-1-isobutoxy butane, malic acid, tetradecanoic acid, phytol acetate, trans phytol, n-hexadecanoic acid, 9Z,12Z-octadecadienoic acid, stearic acid, sitosterol, 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one, 2,4,5-trimethyl-2,4-dihydro-3H-pyrazol-3-one. Conclusion The results of this study suggest that the ethanolic extract of the fruit of Ficus carica may have potential antidiabetic and anti-obesogenic agents.