Current anti-diabetes mechanisms and clinical trials using Morus alba L.

Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia mulberry leaf is used as tea to complement the treatment of diabetes mellitus.The methods by which mulberry leaf affects the body and its mechanism when combined with chemical agents have been studied extensively.Conclusions:We summarize the possible mechanisms of the anti-diabetic effects of mulberry leaf based on extraction procedures,in vitro and in vivo experiments,and clinical trials.We also discuss the hypothesis that crosstalk and“critical nodes”may be useful for a deeper molecular understanding of the treatment and prevention of diabetes with mulberry leaf.

Anti-Tumor and Anti-Diabetic Effects of Sarsasapogenin

In this paper,the pharmacological effects and molecular mechanisms of sarsasapogenin,such as anti-oxidant,anti-inflammatory and anti-diabetic effects,are reviewed in order to provide a theoretical basis for the subsequent development and clinical application of sarsasapogenin.

Access to novel anti-diabetic agents in resource limited settings:A brief commentary

The prevalence of diabetes mellitus is increasing in resource limited settings.Simultaneously,there has been an increase in the number of novel therapies for the management of diabetes mellitus.However,use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings.Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes,and thus most likely to benefit from the therapy,are less likely to have negative budget impact for funders.To improve access,and reduce morbidity and mortality,requires alignment amongst key stakeholders including patient advocacy groups,health care professional councils,national departments of health,the pharmaceutical industry,treasury and finance departments.

Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diab

Endothelial function plays a pivotal role in cardiovascular health,and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity.The nitric oxide-cyclic guanosine monophosphate pathway,prostacyclin-cyclic adenosine monophosphate pathway,inhibition of phosphodiesterase,and the opening of potassium channels,coupled with the reduction of calcium levels in the cell,constitute critical mechanisms governing vasorelaxation.Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes,with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts.A plethora of medicinal plants,characterized by potent pharmacological effects and minimal side effects,holds promise in addressing these concerns.In this review,we delineate various medicinal plants and their respective biochemical constituents,showcasing concurrent vasorelaxant and anti-diabetic activities.

Evaluation of extraction protocols for anti-diabetic phytochemical substances from medicinal plants

AIM To examine the efficacy of three extraction techniques: Soxhlet-extraction(SE), cold-maceration(CM) and microwave-assisted-extraction(MAE) using 80% methanol as solvent. METHODS The study was performed on each of 50 g of Vernonia amygdalina(VA) and Occimum gratissimum(OG) leaves respectively. The percentage yield, duration of extraction, volume of solvent used, qualitative and quantitative phytoconstituents present was compared. The biological activities(hypoglycemic effect) were investigated using albino wistar rat model of diabetes mellitus(n = 36) with a combined dose(1:1) of the two plants leaf extracts(250 mg/kg b.w.) from the three methods. Theextracts were administered orally, once daily for 21 d.RESULTS In this report, the percentage VA extract yield from MAE was highest(20.9% ± 1.05%) within 39 min using 250 m L of solvent, when compared to the CM(14.35% ± 0.28%) within 4320 min using 900 m L of solvent and SE(15.75% ± 0.71%) within 265 min using 500 m L of solvent. The percentage differences in OG extract yield between: MAE vs SE was 41.05%; MAE vs CM was 46.81% and SE vs CM was 9.77%. The qualitative chemical analysis of the two plants showed no difference in the various phytoconstituents tested, but differs quantitatively in the amount of the individual phytoconstituents, as MAE had significantly high yield(P > 0.05) on phenolics, saponins and tannins. SE technique gave significantly high yield(P > 0.05) on alkaloid, while CM gave significant high yield on flavonoids. The extracts from CM exhibited a significantly(P > 0.05) better hypoglycemic activity within the first 14-d of treatment(43.3% ± 3.62%) when compared to MAE(36.5% ± 0.08%) and SE methods(33.3% ± 1.60%). However, the percentage hypoglycemic activity, 21 d post-treatment with 250 mg/kg b.w. extract from MAE was 72.6% ± 1.03% and it was more comparable to 10 mg/kg b.w. glibenclamide treated group(75.0% ± 0.73%), unlike the SE(69.5% ± 0.71%) and CM(69.1% ± 1.03%). CONCLUSION CM technique produces extract with better hypoglycemic activity, whereas; MAE is a better option for high yield of phytoconstituents using less solvent within a short time.

Anti-diabetic and anti-cholesterolemic activity of methanol extracts of three species of Amaranthus

Objective:To investigate the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of Amaranthus caudatus,Amaranthus spinosus and Amaranthus viridis in normal and streptozotocin(STZ) induced diabetic rats.Methods:In this study,the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of all three plants was evaluated by using normal and STZ induced diabetic rots at a dose of 200 mg/kg and 400 mg/kg p.o.daily for 21 days.Blood glucose levels and body weight were monitored at specific intervals,and different biochemical parameters,serum cholesterol,serum triglyceride,high density lipoprotein, low density lipoprotein and very low density lipoprotein were also assessed in the experimental animals.Histology of pancreas was performed.Results:It was found that all the three plants at 400 mg/kg dose showed significant anti-diabetic and anti-cholesterolemic activity(P<0.01),while at 200 mg/kg dose less significant anti-diabetic activity(P<0.05) was observed.Concluslons: Methanol extracts of Amaranthus caudatus,Amaranlhus spinosus and Amaranthus viridis showed significant anti-diabetic and anti-cholesterolemic activity,which provides the scientific proof for their traditional claims.

A comprehensive review on anti-diabetic property of rice bran

Rice bran(RB) is one of the nutrient-rich agricultural byproducts. It is a composite of carbohydrates, lipids, proteins, fibers, minerals, and trace elements such as phosphorus, potassium, magnesium, calcium and manganese. The extraction and purification process influences the quality and quantity of rice bran oil, which is rich in tocopherols, tocotrienols, 毭-oryzanol, and unsaturated fatty acids. The bioactive components of RB have been reported for exhibiting antioxidant, anti-inflammatory, hypocholesterolemic, anti-cancer, anti-colitis, and antidiabetic properties. In vitro and in vivo studies, and clinical trials in human volunteers revealed the anti-hyperglycemic activity of RB derived compounds. An updated comprehensive review on the antidiabetic property of RB and its derivative is required to appraise the current knowledge in the particular field. Thus, the present paper covered the composition and bioactivities of RB, and influence of extraction methods on the biological property of rice bran oil and rice bran extract. And the current review also focused on the reported antihyperglycemia activity of rice bran derivatives, and its probable mechanism.

Novel anti-diabetic agents in non-alcoholic fatty liver disease: a mini-review

BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)encompasses a spectrum that ranges from simple steatosis to non-alcoholic steatohepatitis(NASH)and to cirrhosis.The recommended treatment for this disease includes measures that target obesity and insulin resistance.The present review summarizes the role of newer anti-diabetic agents in treatment of NAFLD.DATA SOURCES:PubMed,MEDLINE and Ovid databases were searched to identify human studies between January 1990and January 2013 using specified key words.Original studies that enrolled patients with a diagnosis of NAFLD or NASH and involved use of newer classes of anti-diabetic agents for a duration of at least 3 months were included.RESULTS:Out of the screened articles,four met eligibility criteria and were included in our review.The classes of newer anti-diabetic medications described were dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 analogues.CONCLUSIONS:Liraglutide and Exenatide showed improvement in transaminases as well as histology in patients with NASH.Sitagliptin showed improvement in transaminases but limited studies are there to access its effect on histology.Further studies are needed to support use of newer anti-diabetic medications in patients with NAFLD.

Anti-diabetic potential of Urena lobata leaf extract through inhibition of dipeptidyl peptidase IV activity

Objective: To evaluate the anti-diabetic potential of leaf extract from Urena lobata(U. lobata) through dipeptidyl peptidase IV(DPP-IV) inhibitory activity.Methods: U. lobata leaf was extracted in hot water and ethanol. The activity of DPPIV inhibitor was tested by in vitro study using gly-pro-p-nitroanilide as substrat of DPPIV and vildagliptin, as standard reference. A product of the reactions between gly-pro-pnitroanilide and DPP-IV, was observed by microplate readers with λ = 405 nm. All data were expressed as mean ± SD and the IC50 value was determined by non linear regression curve fit. Active substances in leaf extract of U. lobata was analyzed by liquid chromatography-mass spectrometry. DPP-IV inhibitory activity of active compounds was evaluated in silico using docking server. Results: The ethanolic extract of U. lobata showed stronger DPP-IV inhibitor activity than water extract with the IC50 values of 1 654.64 and 6 489.88 μg/mL, respectively. Vildagliptin, based on standard reference for DPP-IV inhibitor activity, has IC50 value of 57.44 μg/mL. Based on in silico analysis, mangiferin, stigmasterol and β-sitosterol in U. lobata extract have a strong inhibitory activity on DPP-IV. Conclusions: The results showed that DPP-IV inhibitory activity of U. lobata is related to its active compounds such as mangiferin, stigmasterol and β-sitosterol.

Anti-diabetic and anti-hyperlipidemic effects of sea cucumber(Cucumaria frondosa) gonad hydrolysates in type Ⅱ diabetic rats

The present study investigated the anti-diabetic activity and potential mechanisms of sea cucumber gonad hydrolysates(SCGH)in a rat model of type II diabetes induced by streptozotocin(STZ)combined with high-fat diet(HFD).Results showed that SCGH significantly reduced water intake,fasting blood glucose level and glycated hemoglobin level.Moreover,the oral glucose tolerance,insulin resistance and plasma lipid level in diabetic rats were also alleviated.Furthermore,histological analysis showed that SCGH effectively protected the tissue structure of liver.In addition,mechanism studies showed that SCGH improved glucose metabolism via activating the IRS/Akt signaling pathway,and promoted lipid metabolism via activating the AMPK signaling pathway.In summary,these findings suggested that SCGH have potential anti-diabetic effects by improving insulin resistance and lipid metabolism disorders.

The neuroprotective effects of the anti-diabetic drug linagliptin against Aβ-induced neurotoxicity

Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.

Anti-diabetics and antimicrobials:Harmony of mutual interplay

Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes.The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes,assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation.On a parallel basis,microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment,all of which can be reversed by antimicrobial treatment.Standing at the crossroads between diabetes,immunity and infection,we aim in this review at projecting the interplay between immunity and diabetes,shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents.Furthermore,we focused on the antidiabetic drugs that can confer antimicrobial or anti-virulence activities.

Antioxidants, anti-proliferative, anti-inflammatory, anti-diabetic and anti-microbial effects of isolated compounds from Swertia corymbosa (Grieb.) Wight ex C.B. Clark – An in vitro approach

The present study,antioxidant,enzyme inhibitory,anti-inflammatory and antimicrobial activity of isolated compounds such as Decussatin(1),Gentiacaulein(2),Swertianin(3),1,8-dihydroxy-2,6-dimethoxy xanthone(methylswertianin)(4)8-hydroxy-1,2,4,6-tetramethoxyxanthone(5)and 1,2-dihydroxy-6-methoxyxanthone-8-O--d-xylopyranosyl(6)were investigated using an in vitro model.Results of antioxidant studies revealed that the compound 6 possessed an efficient 2,2-diphenyl-1-picryl-hydrazyl(DPPH•)(IC5007.19±4.56μmol/mL),2,2-azinobis(3-ethylbenzothiozoline-6-sulfonic acid)(ABTS•^+)(42.62±0.25 mmol/L TE/g),superoxide(57.89±3.45μmol/mL),nitric oxide(18.45±1.23μmol/mL)and hydroxyl(12.13±2.76μmol/mL)radical scavenging activities,ferric reducing antioxidant power(14.76±0.10 molar Fe(II)/g),metal chelating(213.85±27.18 mg EDTA/g)ability.Compounds 6 and 3 exhibited significant anti-proliferative activity.Compound 6 displayed strongest antibacterial activity against Streptococcus pneumoniae and Escherichia coli with MIC value of 3.90μg/mL and 21.21±0.25 and 20.27±0.11 mm zone of inhibition at 25μg/mL concentration respectively.In the membrane stabilization and protein denaturation test 3 was the most potent with an IC50 value of 12.57,18.75μmol/mL respectively.

Effects of anti-diabetic drugs on sarcopenia: Best treatment options for elderly patients with type 2 diabetes mellitus and sarcopenia

Human life expectancy increases as society becomes more developed.This increased life expectancy poses challenges associated with the rapid aging of the population.Sarcopenia,an age-related disease,has become a worldwide health issue.Patients with sarcopenia experience decreases in muscle mass and function,becoming frail and eventually bedridden.Type 2 diabetes mellitus(T2DM)is also a major health issue;the incidence of T2DM increases with aging.T2DM is associated with reduced muscle strength and poor muscle quality and may contribute to acceleration of the aging process,augmenting age-related sarcopenia.Recent studies indicate that elderly patients with diabetes are at an increased risk for sarcopenia.Therefore,these older diabetic patients with sarcopenia need specific anti-diabetic therapies targeting not only glycemic control but also sarcopenia,with the goal of preventing sarcopenia in presarcopenic patients.Presently,various types of hypoglycemic drugs are available,but which hypoglycemic drugs are better suited for geriatric T2DM patients with sarcopenia remains undetermined.In this review,we discuss the association between diabetes and sarcopenia in geriatric patients,and how anti-diabetic drugs may influence sarcopenia outcomes.This review will guide clinical workers in the selection of drugs best suited for this patient population.

<i>In Vitro</i>Anti-Diabetic Activities and Phytochemical Analysis of Bioactive Fractions Present in <i>Meriandra dianthera, Aloe camperi</i>and a Polyherb

This paper reports the in vitro anti-diabetic profile of certain medicinal plants traditionally used in Eritrea for the management of type 2 diabetes. The crude methanolic extracts and fractions of Meriandra dianthera, Aloe camperi, a Polyherb and their fractions were investigated. The in vitro screening of the crude extracts has generally elicited a dose dependent α-glucosidase and α-amylase inhibition activities. M. dianthera displayed the highest α-glucosidase inhibitory activity (IC50: 0.074 ± 0.032 mg/mL) at the highest concentration tested (0.800 mg/mL) relative to A. camperi, the Polyherb and Acarbose (IC50: 0.37 ± 0.052, 0.56 ± 0.024 and 0.55 ± 0.029 respectively). The α-glucosidase inhibition activities of A. camperi and M. dianthera, except for the Polyherb and Acarbose, were significantly different (P < 0.05) at various ranges of concentrations (0.025 - 0.800 mg/mL). The percentage α-amylase inhibitions of M. dianthera, A. camperi, the Polyherb and Acarbose, at the highest concentrations (0.800 mg/mL), were 78.3%, 15.9%, 16.4%, and 82.9% respectively. A. camperi and the Polyherb displayed lower α-amylase inhibitory activities (IC50: 1.72 ± 0.06 and 2.57 ± 0.07 mg/mL respectively) compared to Acarbose and M. dianthera (IC50: 0.31 ± 0.01 and 0.43 ± 0.02 mg/mL respectively). For the α-amylase inhibition activity, even at lower concentrations (0.025 mg/mL), there were statistically significant differences (P < 0.01) among the values generated for all the extracts. The in vitro anti-diabetic screening of the fractions, at 0.800 mg/ml, displayed characteristic enzyme inhibition activities. Generally, the non-polar fractions showed higher enzyme inhibitory activities compared to the polar fractions. The most bioactive non-polar fractions, thus, were subjected to GC-MS analysis and presented various essential oils, fatty acid methyl esters (FAMEs) and benzoic acid derivatives in those plants.

Anti-diabetic effects of cold and hot extracted virgin coconut oil

Virgin coconut oil (VCO) has been shown to possess insulinotropic effects shown in isolated perfused mouse islet with hypolipidemic effects. Hot extracted virgin coconut oil (HEVCO) has been shown to possess better antioxidant properties than cold extracted virgin coconut oil (CEVCO). These properties were exploited to study the anti-diabetic effects of HEVCO and CEVCO in diabetic rats. Four groups 8 rats each, first group served as non-diabetic control remaining groups were made diabetic and force fed with 2ml alcoholic extracts of commercial coconut oil (CCO), CEVCO and HEVCO for 21 days. Blood glucose once in 5 days, body weight gain, food intake once in a week and water intake and urine output daily, were monitored. Animals were sacrificed at the end of 21 days. The results indicated HEVCO reduced blood glucose and lipids viz total cholesterol (TC), triglycerides (TG), High density lipoproteins (HDL), Low and Very Low Density Lipoprotein (LDL+ VLDL) and thiobarbutyric acid reactive substances (TBARS) increased the antioxidant status by elevating activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione (GSH) concentration and decresed lipid peroxidation in liver than CEVCO. These beneficial effects may be attributed to increased polyphenolic and other antioxidants content present in HEVCO.

Red honeybush(Cyclopia genistoides)tea mitigates oxidative imbalance and hyperlipidemia,while improving glucose homeostasis in type 2 diabetic rats

Red honeybush tea(RHT)is a tea product developed from Cyclopia spp.which is endemic to South Africa.Aside refreshment,RHT has over the years been used traditionally in the treatment of various diseases including type 2 diabetes.This study investigated the in vivo antioxidant and anti-diabetic activity of RHT concentrated hot water extract in type 2 diabetes(T2D)model of rats.T2D was induced starting with feeding 10%fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin(40 mg/kg body weight(BW)).Five weeks of treatment of RHT led to significant(P<0.05)elevation in serum insulin,pancreaticβ-cell function,HDL-C levels with concomitant decrease in AST,ALT,ALP,urea,CK-MB,fructosamine,total cholesterol,triglycerides,LDL-C,and insulin resistance in diabetic rats.RHT also signifi cantly(P<0.05)decreased MDA levels and enhanced level of GSH,activity of SOD,catalase,GR in most of organs(pancreas,liver,kidneys,and heart).Signifi cantly(P<0.05)improved morphological changes in the islets andβ-cells were observed in rats treated with RHT.The data of this study suggest that RHT demonstrates an outstanding antioxidant and anti-diabetic effects in STZ-induced T2D model of rats.

The dual-function of bioactive peptides derived from oyster (Crassostrea gigas) proteins hydrolysates

Oysters(Crassostrea gigas)have a wide range of functionality due to their nutritional and bioactive components. However, the bioactive peptides of oyster proteins are rarely reported, particularly their antidiabetes effects and antioxidants. Oyster proteins were extracted from fresh oysters using phosphatebuffered saline and simulated gastrointestinal digestion was performed. The degree of hydrolysis(DH), structural characterization, molecular weight(Mw)distribution, free amino acid, anti-diabetic activity, and antioxidant activity were studied during in vitro simulated gastrointestinal digestion. The results showed that the α-glucosidase inhibitory activity, α-amylase inhibitory activity, DPPH radical scavenging activity, and ABTS radical scavenging activity of the oyster protein gastrointestinal digest were increased(P < 0.05)from 0 to 33.96%, from 9.17% to 44.22%, from 9.01 μg trolox/mg protein to 18.48 μg trolox/mg protein, and from 21.44 μg trolox/mg protein to 56.21 μg trolox/mg protein, respectively. Additionally, the DH, β-turn structure, fluorescence intensity, free amino acid, and short peptide content(Mw < 1 000 Da)increased in the simulated gastrointestinal digestion. These results indicate that the digestive hydrolysates obtained from oyster proteins could be used as natural anti-diabetic and antioxidant agents.

Clinical potentials of ginseng polysaccharide for treating gestational diabetes mellitus

Gestational diabetes mellitus(GDM)is the most common glucose metabolism complication or cause of potential impaired glucose tolerance that can occur either before or during pregnancy and lactation.The prevalence of GDM and its related complications in young women is increasing,and this condition may cause serious outcomes and health hazards to the foetus.However,traditional oral hypoglycaemic drugs have potential safety hazards;therefore,it is urgent to develop new,safe,effective,and easily administered agents and remedies.Ginseng polysaccharide(GPS),which is isolated from Panax(P.)ginseng C.A.Meyer,exhibits notably promising biological activities and effects;specifically,it has been shown to lower blood glucose with mild,safe,and nontoxic characteristics,and it can also improve human bodily functions.Hence,we hypothesise that GPS might be used as an additional therapy and candidate agent for treating GDM.This review innovatively summarizes the available reports and evidence from basic studies to analyze the potential for and feasibility of using GPS as a new therapeutic agent for treating GDM.Additionally,for the first time,this review provides a rationale for the use of GPS.Our summarized results show that GPS may be developed as a novel antidiabetic drug and a remedy for use in preventing and treating GDM,with great application prospects.

Chlorogenic acid modulates glucose and lipid metabolisms via AMPK activation in HepG2 cells and shows its anti-hyperglycemic effect on streptozocin-induced diabetic mice

Objective:In this study,we focus on the hypoglycemic effects of chlorogenic acid(CGA)in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation.Methods:The cytotoxicity,glucose consumption and intracellular triglyceride assay were been detected by commercial kits.The western blots were used to detection the associated protein levels after CGA treatment,and the inhibiter blocking experiments were also be done.In vivo experiment,the fasting blood-glucose,lipid metabolism,liver function,insulin resistance,glucose tolerance,and pathological change were assessed on streptozocin induced diabetic mice.Results:We found that CGA exhibited no cytotoxicity at concentrations of 100μM,it caused a significant increasing of glucose consumption and reducing of the PA-BSA induced intracellular TG level on HepG2 cells at 50μM and 100μM treatment,CGA exhibited up-regulating the level of p-AMPK(Thr172)and p-ACC(Ser79)in dose-dependent manners in vitro and in vivo.The stimulating activities of CGA on AMPK were completely blocked by compound c(CC)on HepG2 cells.And the efficacies of CGA on glucose consumption and intracellular TG accumulation were also completely blocked by CC pretreatment.The CGA also exhibited potent anti-diabetic effects with hypoglycemic activity,improve insulin resistance and glucose tolerance,regulate glucose and lipid metabolism and protect the liver function in vivo.Conclusion:Our results suggested that CGA can regulate glucose and lipid metabolism by AMPK activation,and exhibit potent anti-hyperglycemic effect in streptozocin induced diabetes mice,and may be used as a potential effective anti-diabetes drug.