These two compounds pro;erties be prospective candidates for the development of novel antidiabetic Macronutrients for health after Allergen-free environment their toxicitiy and further clinical trials. Protective Anti-diabetic properties of Ati-diabetic against diabetic neuropathy in experimental rats. Detailed Pharmacognostical Studies on Berberis Aristata DC Plant. A significant reduction in plasma glucose concentration was observed revealing the antihyperglycemic effect of the extract. Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi SH, Farhangi A, Verdi A. Rev Bras Farmacogn. Family: MeliaceaeBiophytum sensitivum L.

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Anti-diabetic medications Thank you for Anti-diabetic properties nature. You are using a browser version with limited support for CSS. Anti-diabetic properties obtain the best Anti-diabetic properties, we recommend Prlperties use Anti-diahetic more propertles to Antti-diabetic browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The treatment of diabetes involves the use of herbal plants, attracting interest in their cost-effectiveness and efficacy. An aqueous extract of Persea americana seeds AEPAS was explored in this study as a possible therapeutic agent in rats with diabetes mellitus.

Anti-diabetic properties -

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Download references. This review work was financially supported by two research grants R and R from Beijing Normal University-Hong Kong Baptist University United International College, China. Food Science and Technology Program, Beijing Normal University—Hong Kong Baptist University United International College, 28, Jinfeng Road, Tangjiawan, Zhuhai, Guangdong, , China.

You can also search for this author in PubMed Google Scholar. Correspondence to Baojun Xu. VR wrote the manuscript and BX has been involved in designing, drafting the manuscript and revising it critically. VR and BX have given final approval of the version to be manuscript.

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Vinayagam, R. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr Metab Lond 12 , 60 Download citation. Received : 16 September Accepted : 14 December Published : 23 December Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Download ePub. Abstract Background Natural food products have been used for combating human diseases for thousands of years.

Aim To summarize the roles of dietary flavonoids in diabetes management and their molecular mechanisms. Findings Tremendous studies have found that flavonoids originated from foods could improve glucose metabolism, lipid profile, regulating the hormones and enzymes in human body, further protecting human being from diseases like obesity, diabetes and their complications.

Conclusion In the current review, we summarize recent progress in understanding the biological action, mechanism and therapeutic potential of the dietary flavonoids and its subsequent clinical outcomes in the field of drug discovery in management of diabetes mellitus.

Background Type 2 diabetes mellitus DM is characterized by impaired insulin secretion, and increased insulin resistance or resistance to insulin mediated glucose disposal. Molecular mechanisms of insulin resistance The molecular levels, the mechanisms underlying insulin resistance are being explored.

Regulation of lipogenesis in adipocytes Adipocyte transcription factors such as peroxisome proliferator-activated receptor gamma PPARγ , sterol regulatory element-binding protein SREBP-1c , adipokines like resistin, play crucial roles in adipocyte differentiation, adipogenesis, and accumulation of cellular lipid droplets.

Flavonoids and their effects on diabetes Flavonoids represent a large class of at least phenolic compounds found in fruits, vegetables, nuts, grain seeds, cocoa, chocolate, tea, soy, red wine, herbs and beverage products. Table 1 Important anti-diabetic potential and the underlying mechanism of dietary flavonoids Full size table.

Table 2 The in vitro and in vivo effect on anti-diabetic and underlying mechanism of anthocyanins Full size table. Full size image. References Devendra D, Liu E, Eisenbarth GS. Article Google Scholar Fowler MJ. Google Scholar International Diabetes Federation, Sixth edition.

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Acknowledgments This review work was financially supported by two research grants R and R from Beijing Normal University-Hong Kong Baptist University United International College, China.

View author publications. Additional information Competing interests The authors declare that they have no competing interests. Rights and permissions Open Access This article is distributed under the terms of the Creative Commons Attribution 4.

About this article. Cite this article Vinayagam, R. Copy to clipboard. Contact us Submission enquiries: emily. balangatan springernature. A deficiency of insulin causes lipolysis to occur at an uncontrolled rate which causes the amount of free fatty acids in the blood to rise resulting in a reduction of glucose metabolism in the peripheral tissues The deficit of insulin also causes a reduction of glucokinase enzyme in the liver and the GLUT-4 transporter protein in adipose tissue resulting in an inability of the target tissues to respond normally to insulin.

Impaired secretion of insulin through destruction of the insulin secreting β-cells, and diminished insulin activity through insulin resistance marks the underlying mechanisms of the pathogenesis of type 2 diabetes 9. The mitochondria- endoplasmic reticulum contacts are known as mitochondria-associated membranes MAMs play an important role in the regulation of lipid exchange, signaling of calcium, cell survival, and homeostasis in cellular metabolism.

These MAM contacts are known to contain several insulin signaling proteins such as AKT kinase, mTORC2, PP2A, and PTEN and thus participate in insulin signaling. A growing number of studies have shown that these MAMs are involved in causing dysfunction of the insulin producing β cells, resistance to insulin in the peripheral tissues, leading to type 2 diabetes mellitus miRNAs are small RNA consisting of 20—24 nucleotides that regulates early development, fat metabolism, cell proliferation, differentiation, apoptosis, and death.

Recent studies have shown that these miRNAs contribute to the pathogenesis of type 2 diabetes mellitus and may be developed into new biomarkers As reactive oxygen species impact chemical changes in all cellular components and produce lipid peroxidation, oxidative stress also causes type 2 diabetes mellitus.

As a result, lipid peroxidation is another important cause of type 2 diabetes mellitus In excess amounts of hydrogen peroxide H 2 O 2 , DNA, RNA, and lipids are severely damaged. Catalase CAT is the major H 2 O 2 regulator, and it neutralizes H2O2 by catalytically converting it to water and oxygen.

When catalases CAT are deficient, pancreatic islet-cells are more susceptible to excessive formation of reactive oxygen species ROS and oxidative stress, which leads to pancreatic islet dysfunction and overt type 2 diabetes mellitus In numerous illness states involving oxidative stress as a significant causal factor, such as diabetes and obesity, plasma levels of oxidized low-density lipoprotein oxLDL are elevated Nuclear factor kappa B NF-B , NH2-terminal Jun kinases, and p53 MAPK are transcriptionally regulated pathways that have been considered one of the most important stress-signaling pathways, and oxidative stress plays a role in the development of type 2 diabetes mellitus through their involvement Type 2 diabetes mellitus is linked by decreased physical activity and exercise training, as well as increased sedentary habits, which are linked to elevated indicators of chronic systemic inflammation Proinflammatory molecules such as interleukin 6 IL-6 , C-Reactive Protein CRP , tumor necrosis factor-alpha TNF- and interleukin 1 IL-1 are released into the bloodstream and inside specific organs in this scenario, causing metabolic inflammation IL-1 is involved in the pancreatic autoimmune response, decreasing -cell activity and activating the nuclear factor kappa-light-chain-enhancer of activated B cells NF-B transcription factor, inhibiting -cell function and inducing death.

The importance of the gut microbiota in the development of diabetes has been demonstrated, and new studies suggest that dysbiosis can increase type 2 diabetes mellitus Experiments in animal models showed that a high-fat diet can increase the synthesis of lipopolysaccharide from Gram-negative bacteria by up to thrice, contributing to low-grade inflammation and insulin resistance 20 , Intestinal dysbiosis can also impair short-chain fatty acid production, which is important for gut barrier integrity, pancreatic cell proliferation, and insulin biosynthesis 22 , Dysbiosis can also affect the production of other metabolites such as branched aminoacids and trimethylamine, causing glucose homeostasis to be disrupted and type 2 diabetes mellitus to develop 24 , The clinical consequences of the gut microbiome are still being researched, and more study is needed to better understand the link between gut bacteria and type 2 diabetes mellitus gov, Wiley Online Library and Google Scholar.

Only peer-reviewed scientific journals were considered during the process. Plants with reported antidiabetic phytochemicals along with mechanism of actions have been considered only for the review work.

Of the identified papers and clinical trials records, unique articles were included and reported in this comprehensive review following inclusion criteria. Anoectochilus roxburghii Wall. family: Orchidaceae is a perennial herb which mainly occurs in China, Taiwan, Japan, Sri Lanka, India, and Nepal.

Polysaccharides from A. Kinsenoside, extracted from A. roxburghii was found to demonstrate significant hypoglycemic activity. Previous studies have shown that kinsenoside could help in the restoration of damaged β cells in pancreas and function against oxidative stress and NO factor and also regulates antioxidant enzymes, scavenging of free radicals Bacopa monnieri L.

family: Scrophulariaceae is a creeping herb which occurs across India. Several compounds including tetracyclic triterpenoid saponins, Bacosides A and B, Hersaponin, alkaloids viz. Herpestine and Brahmine and flavonoids have been isolated from the plant Bacosine, a triterpene isolated from the ethyl acetate fraction of the ethanolic extract of B.

monnieri showed pronounced reduction in blood glucose levels in diabetic rats in a dose-dependent mode; however, no such effect has been observed on normal rats. Thus, bacosine is known to possess antihyperglycemic properties rather than hypoglycemic activity.

It has been suggested that bacosine works in a way similar to insulin and that its antihyperglycemic activity might be attributed to the increase in the consumption of peripheral glucose as well as protect against oxidative damage in alloxan induced diabetes. Root extract B.

aristata regulates glucose homeostasis by reducing gluconeogenesis and oxidative stress and exhibits a strong anti-hyperglycemic activity 30 , The major antidiabetic compound extracted from this plant is berberine.

According to 32 , berberine extracted from B. aristata in a manner of 0. Another clinical trial also showed the efficacy of berberine as adjuvant therapy in poorly controlled type 2 diabetic patients In other clinical trials, berberine also showed promising efficacy compared to rosiglitazone and metformin by reducing HbA1c, fasting blood glucose, postprandial blood glucose despite having some adverse effects on liver Moreover, there was a decrease in Hb1Ac level in comparison to baseline and in fasting and postprandial plasma glucose levels in comparison to both baseline and placebo Bixa Orellana L.

The plant originated in Brazil but also grows in South and Central America. Besides, it also occurs in tropical countries such as Peru, Mexico, Ecuador, Indonesia, India, Kenya, and East Africa Orellana lowered the blood glucose levels in dogs with streptozotocin-induced diabetes 36 , It has been suggested that B.

Orellana causes a reduction in blood glucose level by increasing peripheral utilization of glucose 38 , 39 , increasing plasma insulin levels and increasing the binding of insulin to insulin receptors Bixin, a high carotenoid content and a natural pigment found in B. orellana showed prominent hypoglycemic actions.

Bumelia sartorum Mart. It naturally grows from north of Minas Gerias to Piaui An unsaturated triterpene acid named bassic acid, isolated from the ethanol extract of root bark of B.

surtorum exhibited significant hypoglycemic activity in alloxan induced diabetic rat models. Moreover, bassic acid was found to significantly increase the glucose uptake and glycogen synthesis process in isolated rat diaphragm.

In alloxan-diabetic rats following bassic acid treatment, a significant increase in plasma insulin levels was found. It has been suggested that bassic acid increases insulin secretion from pancreatic beta-cells. This could be the underlying mechanism by which bassic acid shows its hypoglycemic property which was found to be approximately equal to that of chlorpropamide Callistemon rigidus R.

family: Myrtaceae is an evergreen plant which is native to Australia. Noteworthy antidiabetic compounds piceatannol and scirpusin B were isolated from the stem bark of the plant using 1 H- and 13 C-NMR technology These compounds can suppress the activity of α- amylase in isolated mouse plasma Methanol extract of C.

rigidus can also demonstrate prominent repressing activity on α- amylase. Besides, scirpusin B can regulate α-amylase in mouse GIT to demonstrate antidiabetic efficacy.

These compounds are also expected to abate increment of postprandial glucose level and can offer a very good wellspring of antidiabetic drug development Catharanthus roseus L.

Don family: Apocynaceae is a shrub-type plant that can grow up to 30— cm in height. The plant originated from Madagascar but is available around the world due to its high survival rate Its leaf extracts exhibited significant dose-dependent blood sugar-lowering activity in normal and streptozotocin-induced diabetic model rats.

The blood sugar-lowering potential of the leaf extract was equivalent to that of the commercially available drug Tolbutamide in the animal models 45 , Comapred to normal animals, the enzymic activities of glycogen synthase, glucose 6-phosphate-dehydrogenase, succinate dehydrogenase and malate dehydrogenase were found to decrease in the liver of diabetic animals and were significantly increased after treatment with dichloromethane—methanol DCMM extract of leaves and twigs of C.

for 7 days. It has been suggested that C. roseus exhibits its anti-diabetic activity by increasing glucose metabolism in treated rats Among isolated compounds, especially alkaloids including vindoline, vindolidine, vindolicine and vindolinine, isolated from Catharanthus roseus leaves induced increased glucose uptake in myoblast C2C12 or pancreatic β-TC6 cells where vindolicine showed maximum efficacy.

First three compounds did not exhibit any cytotoxicity towards pancreatic β-TC6 cells even when administered in the maximum dose of Vindolicine, vindolidine and vindolinine also revealed improved protein tyrosine phosphatase-1B PTP-1B inhibition actions which can play a pivotal role in type 2 diabetes management Chamaemelum nobile L.

It is very much popular throughout Europe, most notably in France and USA Its aqueous extract mitigated blood glucose concentration in streptozotocin induced diabetic rat models except changing plasma insulin level which indicated an insulin secretion independent pathway nobile may also exhibit its hypoglycaemic activity in the gastrointestinal tract by slowing down the digestion process and reducing the rate of carbohydrate absorption Chamaemeloside, 3-hydroxymethylglutaric acid HMG containing flavonoid glucoside is the most notable isolated antidiabetic compound from this plant which revealed hypoglycemic activity in Swiss-Webster mice models by reducing plasma glucose concentration.

The reduction of fasting glucose level and improved glucose tolerance referred that it might act following more than one mechanism The underlying mechanism of action may be attributed to the stimulation of the utilization of peripheral, especially in muscle and adipose tissue.

In 8 week long clinical study on 26 pre-diabetic volunteers 21 were male and 5 were female; mean age: Cichorium intybus L. family: Asteraceae is an erect herb-type perennial plant that grows upto 1 m. It is abundantly found in Asia, Africa, Europe, and Southern America. Its ethanolic extract CIE was found to show a marked reduction in the hepatic glucosephosphatase GlcPase activity when compared to the control group.

The decrease in the activity of hepatic GlcPase could lead to a reduction in the production of hepatic glucose, which in turn reduces the blood glucose level in CIE-treated diabetic rats Chlorogenic acid and chicoric acid are the two most notable antidiabetic phytoconstituents isolated from this plant which can increase glucose uptake in L6 muscular cells.

Both phytochemicals can also upraise insulin secretion from the INS-1E insulin-secreting cell line and rat islets of Langerhans. Besides, chicoric acid can exert both insulin-secreting and sensitizing activities Cinnamomum verum J.

Presl family: Lauraceae is an evergreen plant with a height of m which is local to Southern India and Srilanka. Apart from these places, it is widely available in other Asian, Australian, Caribbean and African countries but most notably in China, Indonesia, Madagascar, Vietnam and Burma.

The name Ceylon came after the former name of Srilanka, its native place. Bark after drying is the most important part of the plant with remarkable medicinal values Methanolic extract from C. verum can suppress the activity of α- glucosidase and α-amylase According to the study, cinnamon aqueous extract also showed notable antidiabetic activity in alloxan induced diabetic rat models by reducing fasting blood sugar, triglycerides and total cholesterol when tested for thirty days long Interestingly, a lower dose of cinnamon extract i.

In another research, it was revealed that hydro-alcoholic extract of Cinnamon can ameliorate postprandial glycemia more than its aqueous extract Cinnamon can also increase the uptake of glucose by upraising the number of insulin receptors, glucose transporter 4 and activating glycogen synthase to diminish glucose levels 56 , Cinnamon extract was also co-administered with other herbals to evaluate the synergistic activity on diabetic complications.

Again, a combination of methanolic cinnamon extract along with green tea can also decrease blood glucose concentration and body weight significantly in streptozotocin induced diabetic rat models by showing synergism 56 , Among isolated phytochemicals, it is believed that cinnamon polyphenols like eugenol and pyrogallol can demonstrate antidiabetic properties by renovating beta cells which leads to hypoglycemic and hypolipidemic actions According to Tulini et al.

solid lipid microparticles SLM of proanthocyanidin rich cinnamon extract can improve the antidiabetic efficacy of foods Again, cinnamaldehyde can ameliorate the uptake of glucose by upraising the amount of AKT2 and aortic nitric oxide synthase 3 eNOS , insulin receptor substrate1 IRS1 and p regulatory subunit of PI3K PI3K-P85 while concurrently abating the expression of NADPH oxidase 4 NOX4 which eventually balance the increased glucose concentration 56 , Cinnamon supplementation at the dose of mg showed prominent antidiabetic action in a 3 month long randomized, triple-blind placebo-controlled, parallel clinical trial in type 2 diabetic patients 63 were male and 75 were female; age range: years by causing a reduction in all glycemic parameters, namely FPG by In a review of 8 randomized-controlled trials, it has been found that sole therapy of powdered or aqueous form of cinnamon, at different doses starting from 0.

Costus pictus D. It demonstrated antidiabetic action by the inhibition of α-amylase and α—glucosidase activity pictus can also improve the secretion of insulin in diabetic rat models along with improvement in glucose utilization It has been found that upon the administration of aqueous extract of C.

pictus to diabetic rats, C. pictus causes a marked reduction in blood glucose levels and an increase in plasma insulin level. pictus Earlier researchers also found that β-amyrin and methyl tetracosanate are the major bioactive phytoconstituents which exhibited ameliorated glucose uptake in 3T3-L1 adipocytes 67 , In another study conducted on C.

pictus , β- L- Arabinopyranose methyl glycoside was reported responsible for antidiabetic property Ingestion of the leaves of C.

pictus by diabetic patients showed statistically significant reduction in their fasting and postprandial blood glucose levels, as per a cross-sectional clinical study Curcuma longa L.

It is grown in tropical regions like Pakistan, China, Peru and India. The curcuminoids bisdemethoxycurcumin, curcumin and demethoxycurcumin were isolated from C. longa and were found to exhibit α-glucosidase inhibitory activity Among the three curcuminoids, bisdemethoxycurcumin showed the most potent α-glucosidase inhibition Besides, volatile oils extracted from both fresh and dried turmeric rhizomes showed potent glucosidase inhibitory activity in a dose-dependent mode, and dried rhizomes increased the glucosidase inhibitory action significantly.

Potent α-glucosidase and α -amylase inhibitory activity was exhibited by Aromatic-Turmerone, the main volatile component in turmeric rhizome Turmerin, a water-soluble protein found in turmeric rhizomes inhibits α-amylase and α-glucosidase activities.

Thus, turmeric rhizomes exert inhibitory action against enzymes related to type 2 diabetes A combination of Curcuma longa and Allium sativum at 2.

In addition, in six clinical trials, treating type 2 diabetic patients with curcuminoids ranging from 0. Improvement in diabetes-associated endothelial dysfunction and hyperlipidemia was observed as well Cryptolepis sanguinolenta , Lindl.

family: Apocynaceae is a scrambling thin-stemmed shrub indigenous to West Africa which is commonly found in tropical rainforests, thickets, and mountainous ecologies It was found to reduce the intestinal absorption of glucose and its transport from the gut significantly in a dose-dependent mode in the normoglycemic rats 76 , The study also revealed that treatment with C.

sanguinolenta increased the size of β cells which might have improved the production and activity of insulin resulting in reduced blood glucose levels. Additionally, C. sanguinolenta also increases the uptake of glucose by 3T3-L1 cells, and improves insulin-mediated disposal of glucose.

The hypoglycemic activity exhibited by the extract of C. sanguinolenta may be due to the presence of its alkaloid constituents.

It has been reported that insulin resistance is reduced by alkaloids in mice and high fat-fed rats. They can activate AMP-activated protein kinase in 3T3-L1 adipocytes and L6 myotubes and promote the translocation of GLUT4 in L6 myotubes in a manner that is independent of phosphatidylinositol 3-kinase.

Besides, they also improve the uptake of glucose in HepG2 and 3T3-L1 cells. In addition, they probably suppress the activity of the α-glucosidase enzyme and cause a reduction in the absorption of glucose. It has also been reported to significantly reduce the plasma levels of IL-6 with increased insulin sensitivity.

This mechanism of action might also be responsible for the hypoglycemic activity of alkaloids-containing C. sanguinolenta stem extract Cryptolepine, an indoloquinoline alkaloid purified from C. sanguinolenta , was found to reduce plasma glucose level significantly in a mouse model of diabetes, and in that model, it was approximately as effective as ciglitazone.

It was suggested that cryptolepine works directly at the cellular level to enhance the glucose transport in 3T3-L1 cells and thus causes a reduction in blood glucose level Euclea natalensis Thunb.

myrtina family: Ebenaceae is a multi-stemmed, dioecious shrub or little tree growing up to about 6 m height. It is distributed in Botswana, Zimbabwe, Namibia, Swaziland, Mozambique and South Africa.

Its crude acetone root bark extract was found to show antidiabetic activity in type 2 induced diabetic rat models Besides, the plant extract of E. undulata was found to inhibit α-glucosidase and α-amylase activity Past studies have revealed the presence of epicatechin and α-amyrin-3O-β- 5-hydroxy ferulic acid in the crude acetone extract of the root bark of E.

It has been reported that epicatechin may have the ability to lower blood glucose levels and α-amyrin-3O-β- 5-hydroxy ferulic acid can inhibit α —glucosidase Gymnema sylvestre R.

family: Asclepiadaceae is an evergreen, woody climber and endogenous plant which is widely available in central and southern India and in the southern part of China, Sri Lanka, Malaysia and tropical Africa, Malaysia sylvestre can improve average blood glucose levels in animal models and can stimulate insulin secretion from the MIN-6, HIT-T15 and RINm5F β-cells by upraising membrane permeability Gymnema sylvestre is thought to act by several mechanisms including regeneration of islet cells, increase in the secretion of insulin and glucose utilization by insulin-dependent pathway, increase the phosphorylase enzyme activity, decrease in gluconeogenic enzymes and sorbitol dehydrogenase, reduction of glucose absorption from the gut wall sylvestre leaves which demonstrated blood glucose level lowering activity in rat models Gymnemic acid is a complex mixture of several more than seventeen saponins which are mainly dammarene and oleanane.

There are also seven novel dammarane saponins from the leaf extract of G. sylvestre known as gymnemasides I-VII. The introduction of gymnemic acid IV can decrease whose efficacy is comparable to the commercially available drug glibenclamide. In addition, the leaf extract of Gymnema sylvestre at mg b.

Such lessening of the fasting blood glucose levels and post-prandial blood glucose levels were additionally consolidated by two other open-label trials on diabetic patients where the leaf extract of G.

sylvestre were administered in the dose of 6—10 g for 15—21 days 86 , sylvestre leaf extract exhibited a better reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma protein levels compared to conventional therapy of tolbutamide or glibenclamide alone.

sylvestre alone even after ceasing their conventional drug therapy A similar open-label study on 27 type 1 diabetic patients observed that the leaf extract supplementation reduced the levels of glycosylated plasma protein and serum amylase and increased serum C-peptide levels in contrast to the conventional therapy alone through the possible mechanism of regenerating the residual beta cells of the pancreas Gynura divaricate L.

It also cultivates in the eastern and northern Taiwan coasts though is widely found in various part of Asia divaricate can improve glucose metabolism in animal models including mice and rats. A study also revealed its low toxicity profile in both in vivo and in vivo testing along with significant reduction of fasting serum glucose and improved pancreatic damage Among hypoglycemic phytoconstituents of the plant aerial part, a few major compounds are nystose, β-D-fructofuranose, 1-kestose, sucrose and 1F-β-fructofuranosylnystose which are fructooligosaccharides.

The hexose transport assay showed that Nystose delivered the most powerful hypoglycemic activity among these five isolated phytocompounds Past studies also suggested that increasing GLUT4 expression promotes the glucose uptake and utilization. Hordeum vulgare L. It was also found to promote glucose uptake and reduce gluconeogenesis by downregulating some genes responsible for gluconeogenesis.

Barley is also rich in magnesium acting as a co-factor for more than enzymes as well as for those which are involved in glucose metabolism and insulin secretion. This could be due to its high fiber content β-glucans from barley also improved glycemic control in diabetic patients, mainly by abating postprandial blood glucose levels, according to multiple clinical studies.

It has been suggested through clinical trials that high β-glucans containing foods have lower glycemic index GI and diabetic people should substitute the high-GI foods in their diet with low-GI foods in order to control the disease 99 , ex DC. It contains Masoprocol, a lipooxygenase inhibitor as the major antihyperglycemic compound which decreased plasma glucose level in type-2 diabetic mice models without changing the concentration of plasma insulin.

Lobelia chinensis Lour. It is a plant from which two new pyrrolidine-type alkaloids, radicamines A and radicamines B, were found to inhibit α-glucosidase activity and demonstrate antidiabetic efficacy Besides, it has also been reported that the active ingredients of 5-hydroxymethylfural and acacetin in L.

chinensis has been shown to promote the secretion of insulin, improve insulin resistance, and stimulate the utilization of glucose by acting on GSK3B, MAPK, INR, and dipeptidyl peptidase-4 DPP4 Lupinus perennis L.

family: Fabaceae is a perennial herb which is abundantly found in Canada and USA It is a plant from the leaves of which the compounds lupanine, a-OH lupanine, and oxo-lupanine were extracted and enhanced the secretion of insulin from isolated rat islets in a glucose-dependent manner.

The fact that a-OH lupanine and oxo-lupanine stimulate insulin secretion only at high glucose concentrations indicates that it would reduce the risk of hypoglycemia which could be of additional value when considering their potential use in the treatment of type 2 diabetes Matricaria chamomilla L.

The same study also reported a significant reduction in oxidative stress related to hyperglycemia A similar study on STZ-induced diabetic rats showed that a 21 day long mg kg- 1 body weight dose of M.

chamomilla leaf extract significantly diminished the fasting blood glucose levels by In addition, another animal study reported the effectiveness of M.

chamomilla flower extract and the isolated compounds quercetin, esculetin, umbelliferone and luteolin in preventing the progression of hyperglycemia. It was observed that quercetin and esculetin moderately inhibited the enzymatic activity of sucrase in rats and all the compounds halted sorbitol from accumulating in the erythrocytes of humans.

Quercetin and the hot water extract also suppressed blood glucose levels in a 21 days long feed test on STZ-induced diabetic rats. Furthermore, esculetin diminished hyperglycemia in a disaccharide loading test on mice.

It was also reported that the extract exhibited good inhibitory activity against the aldose reductase enzyme Apigenin, which is another compound isolated from the plant, showed antihyperglycemic action by causing increment in blood insulin and diminution in blood glucose levels in alloxan induced diabetic mice Moreover, lipid profile was also ameliorated in the patients Momordica charantia L.

family: Cucurbitaceae is a flowering vine cultivated in Asia including Bangladesh, India and in other regions like East Africa and South America as well.

The bitterness becomes more intensified when it ripens. The plant produced notable antidiabetic and hypoglycemic actions which ascertain the adjuvant use of the plant along with conventional commercialized drugs The oral consumption of the juice of M.

charantia seeds showed prominent hypoglycemic activity in streptozotocin induced type 1 diabetic rat models. There are many bioactive phytocompounds isolated from M. charantia producing remarkable antidiabetic activity. Among saponins, 3-hydroxycucurbita-5, dienal-7, di-O-β-glucopyranoside and Momordicine- II were extracted from corolla exhibiting promising insulin-releasing properties in MIN6 β-cells.

Charantin, a cucurbitane type triterpenoid extracted from the same plant has also showed tremendous antidiabetic activity which is even more potent than standard oral hypoglycemic drug tolbutamide Polypeptide-p or p-insulin, insulin-like hypoglycemic protein type substance which demonstrated blood glucose-lowering activity in human upon subcutaneous administration was isolated from corolla.

The insulin mimicking activity of Polypeptide-p can be considered as a plant based alternative of insulin in type 1 diabetic patients Vicine, a glycol alkaloid is another isolated compound from M.

charantia which can promote hypoglycemia in non-diabetic fasting rat models upon intraperitoneal administration Among other isolated compounds, Momordicoside U showed moderate activity during in vitro insulin secretion property screening and 5β,epoxy-3 β,dihydroxycucurbita-6,23 E -diene and 3 β,7 β,trihydroxycucurbita-5,23 E -dienal both revealed hypoglycemic activity in diabetes induced male mice models , A meta-analysis study of ten clinical trials conducted in type 2 diabetic patients observed that M.

charantia possessed significant glycemic control improving ability since it lessened FPG, HBA 1c and PPG levels without causing any side effects.

In addition, prediabetic subjects also had a reduction in their FPG levels , Such action is reported to occur because of increased insulin secretion, as per another randomized-controlled trial. Moreover, anthropometric parameters, namely weight, body mass index, waist circumference, fat percentage were also decreased Another trial on maturity-onset diabetic patients reported the antihyperglycemic action of M.

charantia since it decreased mean blood glucose levels in fasting conditions as well as at 1, 2 and 12 hours after oral intake of 50 g glucose Moringa oleifera Lam. family: Moringaceae is a perennial angiosperm plant native to Asia and greatly found in Malaysia and other tropical countries. Local name of M.

Quercetin and kaempferol, two major phytoconstituents, isolated from M. oleifera notably reduced serum glucose In another study, moringinine, quercetin and chlorogenic acid, notable phytochemicals extracted from this plant were introduced to diabetic rat models to evaluate antidiabetic efficacy.

In addition, in diabetic rats, it also restored the normal histological structure of the pancreas Past studies have indicated that the glucose uptake in the rat soleus muscle is stimulated by kaempferol via the PI3K and PKC mechanisms.

When administered orally, kaempferol was found to reduce fasting blood glucose levels significantly and serum HbA1c levels besides improving insulin resistance.

Additionally, Quercetin blocks the transport of fructose and glucose by GLUT2 in the brain and promotes the translocation and expression of GLUT4 in skeletal muscle In addition, in a randomized control design trial, promising inhibition in the increment of serum glucose after 2h of 75g oral glucose intake was observed after taking capsules processed with M.

oleifera leaf in a population pool of years old The efficacy of M. oleifera in twenty diabetic and ten healthy individuals of 35 to 60 years old was evaluated in another clinical trial.

The concentration of glucose, triglycerides, glycosylated hemoglobin, total cholesterol and low-density lipoprotein cholesterol decreased significantly while high-density lipoprotein cholesterol was upraised. This hypoglycemic efficacy has been assumed to be attributed to phenols, tannins, flavonoids, alkaloids and carotenoids In another study, an assessment was conducted to evaluate the ability of M.

oleifera leaf powder to inhibit the activity of α-amylase in vitro. The study found that M. oleifera leaf powder decreased α-amylase enzyme activity by The study also further evaluated in vivo activity of the leaf powder on postprandial blood glucose levels in the subjects of Saharawi refugee camps 17 diabetic and 10 healthy individuals.

The study displayed that administration of 20g leaf powder improved postprandial glycemic index at 90, and min. as well as improved the mean glycemic index in diabetic patients compared to the control group which indicates the candidacy of M. oleifera as an antihyperglycemic herbal drug Morus alba L.

It is native to China though cultivated sporadically in Japan and Korea Moreover, the alkaloids extracted from the leaves of mulberry were found to exhibit hypoglycemic effects in streptozotocin- STZ- induced diabetic mice.

It has been reported that 1-deoxynojirimycin DNJ , a mulberry alkaloid, reduces the activity of α-glucosidase by competitive inhibition. Upon oral administration of starch and sucrose in Kunming mice, flavonoids from mulberry leaf reduced blood glucose level and inhibited α-glucosidase activity.

In the laboratory experiment, two flavonoids isoquercitrin and astragalin were found to inhibit α-glucosidase activity. Polysaccharides isolated from the leaves of mulberry were reported to reduce plasma glucose level, improve glucose tolerance, increase the hepatic glycogen content, and inhibit α-glucosidase activity.

The extracted polysaccharides α-arabinose, α-xylose, α-glucose, α-rhamnose, and α-mannose were found to repair pancreatic β-cells, resulting in increased insulin secretion and reduced accumulation of liver fat in diabetic rats A randomized, placebo-controlled study on 10 type 2 diabetic age range: 59 —75 years and 10 healthy subjects age range: 24 — 61 years involving the ingestion of 1 g leaf extract of Morus alba showed remarkably reduced blood glucose levels after 2 hours in comparison to the placebo group Another trial showed the effectiveness of the leaf extract in suppressing insulin and postprandial blood glucose levels In addition, fasting blood glucose was better reduced by M.

alba compared to glibenclamide in 24 type 2 diabetic patients 24 male; age range: years , as per a 30 day long randomized controlled trial alba could also be used as a supplementation in the treatment of type 2 diabetes alba in 0.

Such efficacy advocates for the use of 1-Deoxynojirimycin as a dietary supplement in the treatment of diabetes mellitus Nelumbo nucifera Gaertn. Nuciferine, an alkaloid was extracted from the plant through identifying by NMR spectroscopy and was found to increase insulin secretion in both isolated islets and INS-1E cells.

It was found that nuciferine stimulates both the first phase and the second phase of insulin secretion. These results indicated that the nuciferine acts by closing K-ATP channels and also through stimulation of K-ATP channel-independent amplification pathways.

Besides, it shows less cytotoxicity than Glibenclamide In addition, N. nucifera seeds achieved a low glycemic index GI in a randomized crossover trial on healthy subjects Nigella sativa L. family: Ranunculaceae is a herbaceous plant which occurs in several southern Mediterranean and Middle Eastern countries.

It has been suggested that Nigella sativa exhibits its hypoglycemic effect due to the presence of thymoquinone, dithymoquinone, linoleic acid and oleic acid which might be responsible for stimulating pancreatic β-cells causing insulin secretion, reducing hepatic gluconeogenesis, and inducing insulin sensitivity in peripheral tissue.

A placebo-controlled participant blinded clinical study on type 2 diabetic patients found that N. sativa supplementation plays an important role in the amelioration of oxidative stress, the latter being responsible for diabetes mellitus pathogenesis. It has been found that the former does so by improving total antioxidant capacity, glutathione and superoxide dismutase values.

The same study perceived that reduction in insulin resistance was also significant in the diabetic patients in the group taking N. sativa supplementation compared to the placebo group Supplementation of Nigella sativa in type 2 diabetes patients was found to improve fasting blood glucose, HbA1c, total- cholesterol, and LDL level significantly As such, a systematic review done to assess the effect of N.

sativa on type 2 diabetes mellitus has also suggested that it could be adjunctively used with other oral antidiabetic medications to manage the disease Panax ginseng C. It is a plant that has been reported to modify blood glucose levels by increasing insulin sensitivity, ameliorating the function of pancreatic β-cells, and stimulating glucose uptake by elevating the production of glucose transporters GLUT.

The berry extract of P. ginseng stimulates the β-cell proliferation leading to increased insulin secretion to control the level of blood glucose in streptozotocin STZ -induced diabetic mice. Ginseng is known to contain ginsenosides, a group of steroidal saponins, including neutral ginsenosides and malonyl ginsenosides.

Ginseng and neutral ginsenosides were found to lower blood glucose, increase insulin sensitivity, regulate lipid metabolism, and reduce body weight , The study results suggest that malonyl ginsenosides could be used to treat type-2 diabetes.

In addition, a meta-analysis of sixteen clinical trials revealed that Ginseng caused a significant reduction in fasting blood glucose levels in both diabetic and non-diabetic patients, while the other glycemic parameters were contradictory in terms of outcomes Pandanus amaryllifolius Roxb.

family: Pandanaceae is a shrub native to Thailand. This plant is also known as Pandanus odorus. In recent studies, P. amaryllifolius exhibited very prominent hypoglycemic activities.

The root extract of the plant evidently lowered blood glucose levels in streptozotocin induced mice models. The leaf extract could also show promising antihyperglycemic activity by stimulating insulin production and glucose uptake along with inhibition of α-glucosidase enzyme Upon oral administration, this moiety upraised serum insulin and liver glycogen level in normal rat models A clinical study performed on 30 healthy subjects 15 were male and 15 were female; age range: years showed that intake of 30 g of P.

amaryllifolius containing tea caused a significant lessening of postprandial blood glucose Punica granatum L. The fruit aqueous extract of P. granatum can notably decrease fasting glucose level along with promising increment in the expression levels of Glut-4, Glut-2, Akt and IRS-1 followed by improved glucose uptake and its storage in alloxan induced male Wistar rat models It is blessed with several polyphenolic compounds like punicalagin, valoneic acid dilactone, anthocyanin, phenolic and non-phenolic Acids, Glutenins and Tannins Among those, valoneic acid dilactone is the main antidiabetic principle which showed its antidiabetic efficacy by inhibiting the activity of aldose reductase enzyme in a dose dependent pattern.

Protein tyrosine phosphatase 1B PTP1B was also inhibited by valoneic acid dilactone which can also ameliorate the level of blood glucose in alloxan induced diabetic rat models. Other possible mechanisms attributed to antidiabetic action of valoneic acid dilactone may be attributed to improved insulin secretion from rom pancreatic β cells or its release from the bound form along with insulin-mimetic actions or amended glucose utilization technique In addition, an 8-week long double blind randomized-controlled clinical study on 52 type 2 diabetic patients with obesity 26 were male and 26 were female; age range: years found that supplementation of P.

granatum significantly reduced fasting blood glucose from An increase in GLUT-4 gene expression was also observed in the patients Furthermore, another single-blind, randomized-controlled clinical study conducted on 44 type 2 diabetic patients 23 were male and 21 were female; age range 56 ± 6.

Pongamia pinnata L. It occurs throughout India, and mainly found in tidal forests of India. The flowers of P. pinnata reportedly possessed anti-hyperglycemic and anti-lipidperoxidative properties It has been found that oral administration of the aqueous PPAE and ethanolic PPEE extracts of the leaves of P.

pinnata PPEE in alloxan diabetic rats resulted in a pronounced reduction in the plasma glucose level. This may be attributed to the enhancement of the effect of insulin by increasing the insulin release from the pancreatic β-cells or its release from the bound insulin.

The significant glucose-lowering effect of PPAE and PPEE could also result from increased peripheral glucose utilization Karanjin, one of the isolated compounds from this plant was reported to possess hypoglycemic activity in normal and in alloxan-induced diabetic rats.

Pongamol and karanjin extracted from the chloroform-soluble fraction of the ethanolic extract of P. pinnata fruits exhibited significant glucose-lowering activity The underlying mechanism of anti-hyperglycemic activity of the compounds may be attributed by the inhibition of PTPase-1B, a major mediator of insulin signaling and insulin resistance Psacalium peltatum Kunth Cass.

Peltalosa, an ulopyranose compound, has been obtained from the roots and rhizomes of P. peltatum which has showed anti-hyperglycemic activity on mice with mild diabetes, although the efficacy decreased on mice models with severe diabetes The hypoglycemic effect of the compound was reported to be similar to tolbutamide, and the possible underlying mechanism of action could be attributed to enhanced secretion of insulin from the islets of Langerhans or an increased utilization of glucose by peripheral tissues Silybum marianum L.

Its major component is silymarin, a mixture of silibinin silybins A and B , isosilybin isosilybins A and B , silychristin and silydianin Administration of silymarin in patients with type 2 diabetes resulted in a significant reduction in HbA1c level, fasting plasma glucose FPG , daily blood glucose average and glucosuria, daily insulin requirement, fasting insulin, as well as an increase in serum glutamic oxaloacetic transaminase SGOT , serum glutamic pyruvic transaminase SGPT and HDL levels.

When silymarin was supplemented with glibenclamide in type 2 diabetes patients, a reduction in postprandial hyperglycemia was also observed It has been suggested that silychristin A exerts its glucose-lowering effect by protecting the β-cells from oxidative stress-induced damage and blocking the activity of the α-glucosidase enzyme Swertia chirayita Buch Ham.

Promising antidiabetic efficacy of S. chirayita with improved insulin secretion was reported during cell line based evaluation technique using insulin secretion from monolayers of BRIN-BD11 clonal pancreatic cells There are several antidiabetic compounds found in this species exerting prominent antidiabetic efficacy.

According to , 1,5,8-trihydroxy methoxyxanthone extracted from the aerial parts and roots of the S. chirata can demonstrate antidiabetic efficacy by lowering blood sugar levels Gentianine, another antidiabetic compound of this plant is the active metabolite of swertiamarin and is believed to attribute to the efficacy of swertiamarin Promising amelioration in adipogenesis associated expression of PPAR-γ, GLUT-4 and adiponectin by gentianine administration expressed that the compound is responsible for antidiabetic efficacy of swertiamarin.

Magniferin, a potent phytoconstituent found in S. chirata can also exhibit antihyperglycemic potentiality by exhibiting glucosidase and 2,2-diphenylpicrylhydrazyl radical inhibition action. Besides, as a co-therapy with metformin and gliclazide it cured renal injury symptoms due to diabetic neuropathy Moreover, compounds, found in S.

chirata like amarogentin is used in the preparation of different forms of commercially available drugs to treat diabetic complications A 30 day long clinical study done on 12 type 2 diabetic patients found that ingestion of S.

chirayita in grounded powder form caused A reduction was also noticed in lipid profile total cholesterol by 8. Syzygium cumini L. The seeds of S. cumini are thought to lower blood sugar levels by increasing either insulin secretion from β-cells of the islets of Langerhans of Pancreas or its release from the bound form.

Mycaminose, isolated from the seeds of S. cumini was found to produce a remarkable reduction in blood glucose level It was suggested that the mode of action of mycaminose is similar to Glibenclamide, a commercially available anti-diabetic drug Tinospora cordifolia Willd.

It has exhibited blood and urinary glucose-lowering activity along with suppression in the increase of blood glucose level in animal models , It is considered as an antidiabetic herbal drug in the Indian Ayurvedic Pharmacopoeia too due to its alkaloids, diterpenoids and glycosidic constituents.

Among the alkaloids, magnoflorine was found to be the most potent α-glucosidase inhibitor Besides, a norclerodane diterpenonoid, tinosporaside, extracted from T. It has been found that the isoquinoline alkaloid rich fraction AFTC isolated from the stem of T.

cordifolia AFTC significantly reduced the synthesis of glucose in rat hepatocytes like insulin did and it also stimulated secretion of insulin in RINm5F cells like tolbutamide. The underlying mechanism may be attributed to the promotion of insulin release and insulin-mimicking activity In addition, the powdered stem of T.

Trigonella foenum-graecum L. family: Fabaceae known as Fenugreek or Methi is a legume and a popular seasoning worldwide to improve the taste and flavor of food Its seed water-soluble compound GII extract when administered for 15 days in the subdiabetic and moderately diabetic rabbits and for 30 days in the severely diabetic rabbits resulted in the elevation of hepatic and muscle glycogen content, stimulated hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucosephosphate dehydrogenase, superoxide dismutase, glutathione peroxidase, and reduced the activity of glucosephosphatase, sorbitol dehydrogenase, aldose reductase.

Partially damaged pancreatic cells were also regenerated following the administration of GII Trigonelline, nicotinic acid and coumarin are antidiabetic phytochemicals that were isolated from Fenugreek seed. These three antidiabetic compounds extracted from fenugreek showed prominent efficacy in alloxan induced severe and moderate diabetic rabbit models A meta-analysis on 10 clinical trials conducted on type 2 diabetic patients revealed that fenugreek can significantly improve glycemic control by altering parameters, namely fasting blood glucose level by As per a 2 month long double blind placebo controlled trial on 25 subjects with type 2 diabetes mellitus, hydroalcoholic extract of fenugreek seed also decreased insulin resistance compared to control which was apprehended by an increase in insulin sensitivity percentage Vitis vinifera L.

However, it is cultivated worldwide which makes it the largest fruit crop in the world. It contains many active components in its seed and skin, including polyphenols, flavonoids, proanthocyanidins, anthocyanins, procyanidins, and resveratrol, a stilbene derivative The kir6. It has been shown that congenital hyperinsulinism is caused by a mutation in this gene and has a significant role in the development of type-1 diabetes.

Pterostilbene has promising inhibitory efficacy on both normal and mutant models of kir6. Again, quercetin, myricetin and resveratrol are three other most notable polyphenols found in red grapes to treat diabetic complications.

Quercetin can demonstrate improved expression of adiponectin in white adipose tissue and blood concentration, despite inhibition of poly ADP-ribose polymerase γ expression followed by improved insulin sensitivity Quercetin can also inhibit glucose uptake at the level of glucose transporters GLUTs Besides, to treat hyperglycemia, Myricetin is also used as traditional medicine in northern Brazil.

Myricetin can promote glucose uptake in the liver and soleus muscles as well as hepatic glycogen synthase Myricetin can also improve insulin resistance in fructose chow-fed rat models In addition, it can also halt advanced glycation end products in diabetic conditions Furthermore, antihyperlipidemic and human pancreatic alpha-amylase inhibitions are a few other promising mechanisms by which myricetin can produce a significant antidiabetic effect Resveratrol, a phytochemical from stilbene class of polyphenolic compounds isolated from red grape can also demonstrate strong antidiabetic activity.

It can also protect against diabetic nephropathy while administration of resveratrol along with protective activities in renal dysfunction and oxidative stress Resveratrol can effectively restore cellular homeostasis by activating the redox plasma membrane system, which functions as a compensatory mechanism in the cell to preserve redox status , Besides, resveratrol administration to diabetic rats has resulted in decreased concentration of glycosylated hemoglobin The antihyperglycemic efficacy of resveratrol, demonstrated in diabetic animals has been suggested to be due to the stimulatory activity on the transportation of intracellular glucose.

The involvement of resveratrol can also promote glucose uptake in diabetic rat models Improved expression of the insulin-dependent glucose transporter GLUT4 was reported after ingestion of resveratrol in the study conducted on diabetic rat models , Resveratrol was also reported to modulate the function of sirtuin-1, which ameliorates homeostasis of whole-body glucose and insulin sensitivity in diabetic rats Moreover, in a 3 month long randomized controlled clinical trial on 62 subjects with type 2 diabetes mellitus age range: years , resveratrol supplementation exhibited antihyperglycemic action by lowering the value of hemoglobin A1c compared to the control 9.

In another 45 days long randomized double-blinded placebo-controlled parallel clinical study on 66 subjects age range: years with type 2 diabetes mellitus, 1 g daily resveratrol supplementation exhibited antihyperglycemic action by lowering the values of fasting blood glucose, hemoglobin A1c, insulin secretion, and insulin resistance compared to baseline Rhizome serves as the edible and medicinal part of the plant.

Its administration to streptozotocin STZ -induced diabetic rats was found to reduce serum glucose, cholesterol and triacylglycerol levels significantly. Besides, raw ginger also exhibited effectivity in reversing diabetic proteinuria in diabetic rats Several active constituents have been isolated from Ginger including gingerols and their related dehydration products, the shogaols, as well as volatile oils including sesquiterpenes, such as β-bisabolene and monoterpenes, mainly geranial and neral A previous study revealed that 6-shogaol and 6-gingerol can suppress the development of diabetic complications as well as advanced glycation end products AGEs by arresting methylglyoxal, the precursor of AGEs Furthermore, 6-paradol considerably decreased the concentration of blood glucose in high-fat diet-fed mouse models Besides, 6-gingerol, in type 2 diabetic mice, aided glucose-stimulated insulin secretion and improved glucose tolerance by upraising glucagon-like peptide 1 GLP A meta-analysis study on 10 randomized-controlled clinical trials conducted on type 2 diabetic subjects revealed that ginger improves glycemic control by lowering fasting blood glucose and HbA1c levels.

Insulin sensitivity was also improved. Lipid profile improved as well Moreover, the supplementation of ginger improved the recovery of inflammation in type 2 diabetic patients in a randomized-controlled clinical trial, suggesting that the supplementation could help lessen diabetes associated chronic complications Researchers suggested that there are almost dietary and non-dietary plants with antidiabetic properties So it is not possible to describe every plant and its isolated bioactive phytochemicals in a single study.

However, a few more notable antidiabetic plants along with their phytochemicals and possible antidiabetic actions are summerized in Table 1 in addition to the aforementioned plants. Table 1 Plants with antidiabetic properties along with responsible phytochemicals and clinical trial studies.

Mammalian α glucosidase, a membrane-bound hydrolytic enzyme found in the mucosal brush border of the epithelia of the small intestine plays a key role in carbohydrate digestion.

Inhibitors of this α glucosidase enzymes delay the cleavage of carbohydrates resulting in reduced glucose absorption and an attenuated postprandial glycemic level. Thus, α glucosidase inhibitors could show a beneficial effect in the management of non-insulin-dependent diabetes mellitus NIDDM by causing a reduction in postprandial blood glucose levels , Glucagon like peptide-1 GLP-1 and Glucose dependent insulinotropic polypeptide GIP are incretin hormones which can initiate the differentiation of β-cells, stimulate the biosynthesis and secretion of insulin and inhibit gastric emptying.

However, these hormones are rapidly broken down by a serine peptidase enzyme known as dipeptidyl peptidase-4 DPP Therefore, inhibitors of DPP-4 can be used in the treatment of type 2 diabetes. These DPP-4 inhibitors exhibit their antidiabetic activity via prolongation of GLP-1 and GIP activity, stimulation of insulin release and inhibition of glucagon secretion which ultimately leads to regulation of the blood glucose level , Hydrolysis of α-1,4-glucan polysaccharides, such as starch and glycogen is carried out by the enzyme, α-amylase which is found mainly in the saliva and pancreatic juice.

Inhibition of this enzyme helps in the prevention of high postprandial blood glucose levels These increased intracellular calcium levels stimulate the secretion of insulin from pancreatic β-cells. This may also lead to a rise in cAMP via the inhibition of phosphodiesterase , Some phytochemicals improve the sensitivity of non-pancreatic cells to insulin resulting in improved glycemic control.

In skeletal muscle and adipose tissue, glucose uptake is enhanced via the activation of a series of events which take place following an increase in insulin levels. As a result, GLUT4, insulin-regulated glucose transporter protein is recruited to the cell membrane and an increase in the uptake of circulating glucose by the muscle cells and adipose tissue occurs via facilitated diffusion through GLUT4 transporter protein β-cells from the pancreas secrete the hormone insulin which is crucially salient in maintaining homeostasis for glucose metabolism in the body.

β-cells are impaired in type 1 diabetes due to macrophage, cytokine and T-cell mediated autoimmune reactions. In the case of type 2 diabetes, β-cells could possibly be debilitated or rendered dysfunctional due to factors like oxidative stress, enduringly elevated glucose or lipid levels, and the release of the inflammatory mediators.

To inhibit such destruction, β-cells can be fortified against reactive oxygen species ROS accretion and lipid peroxidation mediated cell death by augmenting both non-enzymatic e. In addition, increment of the secretion of β-cell anti-apoptotic genes e.

Suppression of the deterioration of β-cell through these mechanisms halts reduced insulin secretion, thereby avoiding the state of hyperglycemia , Since diabetes mellitus is a condition where blood carbohydrate concentration increases, the monosaccharides nonenzymatically react with the proteins in blood mainly hemoglobin A and albumin and adheres to form a modified protein complex Schiff base through a process called glycation.

The produced glycated hemoglobin HbA1c and glycated plasma proteins are concerned with much significance in the research. HbA1c value is often examined as it is one of the major markers for the diagnosis of diabetes mellitus.

These glycated products can further encounter intramolecular rearrangements followed by other irreversible reactions condensation, cross-linking, glycoxidation, cyclization, dehydration, etc. to become advanced glycation end products AGEs which can accumulate and cause deleterious effects on metabolic and vascular health, leading to added diabetic complications.

Glycation inhibitors hinder this process through various mechanisms, namely competitively binding with the amino group of the protein, binding at the site of glycation, cutting the open chain structure of monosaccharides and, adhering to the intermediaries of the glycation reaction.

Hence, the concentration of HbA1c and glycated plasma proteins is lessened and the aftermath of glycation and diabetic complications can be avoided — Glucagon-like peptide-1 GLP-1 is a hormone secreted by the L cells in the distal ileum and colon of the gastrointestinal system.

Secreted upon nutrient intake, GLP-1 subsequently binds to GLP-1 receptor a G-protein-coupled receptor on pancreatic β-cell to exert its effects, namely, raising the glucose-dependent secretion of insulin and lessening the secretion of glucagon, decelerating gastric emptying, subduing of appetite with imparting a feeling of fullness.

Circulatory GLP-1 faces immediate degradation by the enzyme dipeptidyl peptidase 4 DPP-4 and hence has a short half life of about 2 min. As such, alternative compounds with the functionality of serving as agonists to GLP-1 receptor GLP-1R and being resistant to degradation by DPP-4 enzyme have been recognized feasible to employ the proper effect of GLP ATP synthesis is also enhanced in mitochondria.

As a result, insulin secretion capability and reserve of β-cell is maintained. Glucagon secretion is inhibited by GLP-1R agonists either directly by acting on α-cells of the pancreas, or less likely indirectly along with the stimulated secretion of insulin.

This inhibition ameliorates glycemic control as reduced glucagon level diminishes glucose production from the liver, which in turn reduces the required insulin in the bloodstream. Enhancement of GLP-1 also facilitates the indirect suppression of gastric emptying through the vagus nerve and its involvement with the central nervous system CNS located GLP-1Rs, thus relaying a sensory message to the brainstem , Belonging to the group of sugar transporter proteins GLUT1-GLUT12, and HMIT , glucose transporter type 4 GLUT-4 is a transmembrane domain containing transporter which allows insulin induced blood glucose influx into skeletal muscle and fat cells through facilitated diffusion process and hence maintains the homeostasis of glucose metabolism in the body.

The transporter typically resides intracellularly but relocates to the cell membrane upon stimulation of insulin or during exercise through independent mechanisms. The receptor binding of insulin in target cells activates insulin receptor IR tyrosine kinase, thus beginning phoshphorylation of tyrosine moiety of insulin receptor substrate proteins IRS followed by phosphoinositide 3-kinase PI3K recruitment.

Rab proteins Rab8 and Rab14 lead to GLUT-4 translocation into the cell membrane from intracellular GLUT4 storage vesicle GSV which increases glucose internalization up to times , Based on previous research studies, few phytochemicals have been already recognized as the most prominent antidiabetic lead compounds.

Those are currently under exclusive assessment so that novel antidiabetic drugs can be introduced in the coming days. In Tables 2 — 5 the few most prominent phytochemicals with the reported mechanism of actions are represented briefly.

Alongside these phytochemicals, concerned researchers should also evaluate other aforementioned phytochemicals in this review work to establish absolute safety and toxicity profile as well as the mechanism of antidiabetic actions.

Table 2 Antidiabetic potential of alkaloids extracted from medicinal plants and their mechanism of actions. Table 3 Antidiabetic potential of phenolics extracted from medicinal plants and their mechanism of action. Table 4 Antidiabetic potential of terpenes extracted from medicinal plants and their mechanism of actions.

Table 5 Antidiabetic potential of other notablephyto compounds extracted from medicinal plants and their mechanism of actions. Diabetes is conventionally treated and managed by taking synthetic antidiabetic medications commercially available in the market.

The major classes among these medicines are sulphonylureas glibenclamide , biguanides metformin , thiazolidinediones pioglitazone , DPP-4 inhibitors sitagliptin , alpha-glucosidase inhibitors acarbose , glinides repaglinide and GLP-1 agonists exenatide 7 , Despite the mass prevalence and usage, the synthetic drugs accompany various side effects which include hypoglycemia for sulphonylureas, glinides , weight gain for sulphonylureas, thiazolidinediones , cardiovascular risk for sulphonylureas, thiazolidinediones , pancreatitis for DPP-4 inhibitors, GLP-1 agonists , hepatitis for thiazolidinediones, DPP-4 inhibitors , cancer risk for DPP-4 inhibitors, GLP-1 agonists , gastrointestinal effects for biguanides, GLP-1 agonists , lactic acidosis for biguanides These adversities and constraints associated with the prevailing synthetic medications entail the researchers to search for antidiabetic drugs from plant sources with a better safety and efficacy profile.

Along the lines of many other diseases, diabetes mellitus has been treated with plant based medications for a long while owing to factors like marked efficacy, less toxicity and side effects, low cost, and availability , An exclusive development of plant based drugs has seemingly occurred through evolutionary mechanisms, imparting the capability to interact with biomolecules , Isolated phytochemicals are either used as drugs or availed as chemical leads or their analogs for synthesizing biologically active compounds.

As an example, metformin, the extensively used drug in treating type 2 diabetes, is a drug derived from the plant Galegine officinalis Antidiabetic action being one of the most popular fields of use of phytochemicals houses compounds from various chemical classes, namely flavonoids quercetin , alkaloids berberine , terpenes thymoquinone , phenylpropanoids chlorogenic acid and others.

The phytochemicals reported in this study revealed prominent antidiabetic action through various mechanisms like inhibiting α-glucosidase, α-amylase and DPP-4 enzyme, increasing insulin sensitivity and secretion, increasing glucose uptake by muscle cells and adipose tissue, nourishing pancreatic β-cells, etc.

These various ways of phytocompounds to exert antidiabetic action illustrates the effectual diversity they can offer. Thus, potential phytocompound s , isolated from medicinal plants or dietary materials, with proven preclinical and clinical antidiabetic efficacy can be the prospective and potential candidates for the development of novel antidiabetic drugs.

For example, Charantin and Polypeptide-p isolated from Momordica charantia L. have been reported to exhibit potential antidiabetic activities in preclinical and clinical studies which have been included in this manuscript.

These two compounds can be prospective candidates for the development of novel antidiabetic medicaments after confirming their toxicitiy and further clinical trials.

Traditional medicinal approaches like Ayurveda, Unani and so on also utilized plant based remedies to treat diabetic illness.

However, further research is necessary to disclose the absolute and exact mechanism of action of these compounds which would facilitate their outset as drugs or chemical leads.

Indeed, serving as drugs or drug templates is not the only purpose of plant derived compounds, rather, they also guide in the recognition and revelation of complex and novel molecular pathways and targets involving the health condition Hence, further research on these phytochemicals could enable the discovery of several targets for therapeutic intervention against diabetes mellitus.

In addition, elucidation of the feasibility and toxicity profile despite the mentioned predating advantage as plant based products is also a salient research concern. The two most pronounced variations of diabetes are Type 1 diabetes mellitus and Type 2 diabetes mellitus both of which result in a hyperglycemic state.

Type 1 diabetes mellitus is an autoimmune illness typified by the demolition of pancreatic β-cells followed by dreadful insulin scarcity. However, it is a non-communicable illness, experts are warning us about a figure of almost million diabetic patients in 7 which considers the dreadfulness of this disease.

In a broader sense, the causative factors of diabetes can reside in insulin resistance, abnormal insulin secretion and hepatic glucose synthesis along with impaired fat metabolism.

Insulin resistance refers to the state where the efficacy of the insulin on target tissues becomes compromised particularly on adipocytes, hepatocytes and skeletal muscles which leads to hyperglycemia by impairing utilization of glucose and increasing hepatic glucose output

Open Annti-diabetic. Submitted: 23 September Properteis 05 February com customercare cbspd. Anti-diabetic properties reports Allergen-free environment Wellness annual incidence rate of diabetes mellitus will increase in the future worldwide, especially in the developing countries [ 1 ]. The effects of diabetes mellitus include long-term damage, dysfunction and failure of various organs.

Anti-diabetic properties -

Thus, the extract showed hypoglycemic and hypolipidemic potentials. Though the level of insulin was not assessed in this work, probably, the lack of insulin in the condition of diabetes is the cause of elevation in triglycerides and cholesterol The results of this work show the antidiabetic property of the crude extract in diabetes-induced rats.

Many pancreatic and extra-pancreatic mechanisms may be involved in acting synergistically to induce potent antidiabetic property. This work shows that glibenclamide and the extract possibly adopt a similar mechanism to produce the hypoglycemic effect in rats.

This work also suggests that the extract is valuable in controlling biochemical parameters connected with DM, such as glycosylated hemoglobin, creatinine, serum urea, triglycerides, cholesterol, and also properties of liver enzymes like ALP and ALT.

This work shows scientific confirmation that the use of S. adenotrichum that is rich in important phenolic compounds can be used as a therapeutic source for diabetes. It is suggested to carry out long-term research work to recognize and isolate the active moiety responsible for antidiabetic property and to expose the real mechanism involved in glucose- and lipid-lowering properties of the plant.

The datasets generated for this study are available on request to the corresponding author. The animal study was reviewed and approved by the ethical committee of the Department of Zoology, University of Malakand. AZ: conceptualization. IS: data curtain. DN: formal analysis.

AM: funding acquisition. DN and AZ: investigation. AZ: methodology. AM: project administration. IS: resources. AM: supervision. IS: validation. DN: writing—original draft. AZ: writing—review and editing, revision. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

We are grateful to the Department of Biotechnology and the Department of Zoology, University of Malakand for providing facilities to conduct this work. Riaz S, Skinner V, Srai SK.

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Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes. Diabetes Res Clin Pract. Keywords: diabetes mellitus, Sedum adenotrichum , glibenclamide, alloxan, α-glucosidase.

Citation: Naz D, Muhamad A, Zeb A and Shah I In vitro and in vivo Antidiabetic Properties of Phenolic Antioxidants From Sedum adenotrichum.

Received: 26 September ; Accepted: 04 November ; Published: 27 November Copyright © Naz, Muhamad, Zeb and Shah. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY.

The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. Export citation EndNote Reference Manager Simple TEXT file BibTex. Check for updates. ORIGINAL RESEARCH article. Introduction Diabetes mellitus DM is a global issue. Materials and Methods Plant Collection S.

The figure shows a well-defined boundary with the Islet cells proportionally distributed. The β-cells pointed with black double arrows occupy the core of the Islets, sandwiched by the non-β-cells α-cells, δ-cells, and PP-cells, pointed with orange-colored single arrows which dominate most portions of the peripheries.

In contrast, Fig. The boundaries are adversely affected, with a markedly reduced number of β-cells and randomly scattered non-β-cells. Compared to the negative control 7B , these micrographs show regeneration and restoration into near-intact Islets, similar to the normal control 7A.

The double-arrowed lines point to the β-cells while the single-arrowed lines point to the non-β cells. Hepatic glucose production was significantly lowered in all the treated animals 8A.

Figure 8. Time-course of hepatic glucose production 8A1 vs. Figure 9 A represents glucose absorption by whole intestines following a day pretreatment with LTE. Glucose absorption by the intestines from LTE-treated rats was significantly lowered, relative to control levels.

Inhibition of absorption in rats pretreated with metformin was also statistically significant, unlike that of glibenclamide. Effects of LTE on in-vivo intestinal glucose absorption A with time-course insert, 9A1. Figure 9 B shows glucose absorption by intestinal sacs with a time-course insert, 9B1.

the normal control group. Figure 9 B with time-course insert 9B1 is a result of LTE modulation of glucose absorption by rat intestinal sacs.

The peak time T max for glucose absorption ex-vivo was minutes. Glucose absorption was significantly reduced by direct application of equivalents of LTE medium and high concentrations to the intestinal sacs 9B. LTE low concentration did not seem to alter glucose absorption by the intestinal sacs.

Unlike glibenclamide, glucose absorption was significantly lowered for intestinal sacs containing metformin. Type-2 diabetes continues to pose adverse microvascular and macrovascular challenges to patients, despite the availability of several orthodox antidiabetic medicines. Patients suffer from complications and adverse side effects, eventually requiring insulin shots, due to inadequate glycemic controls with the oral hypoglycemics [ 6 , 7 ].

Plant-based therapies serve as alternatives but usually with a paucity of scientific evidence of efficacy. Given the scantiness and inconsistencies in the scientific evidence on the antidiabetic properties of L. taraxacifolia , the STZ-NAD model of type-2 diabetes [ 45 ] was used in this study to examine the effects of L.

taraxacifolia extract on blood glucose. This study was also designed to further investigate the potential mechanistic targets of LTE in blood glucose regulation as well as its effects at the histological level. Phytochemicals act as plant fingerprints [ 35 ] and offer lead compounds to develop conventional medicines [ 29 ].

The phytochemical analyses revealed the presence of alkaloids, saponins, glycosides, tannins, phytosterols, diterpenes, and flavonoids.

These are secondary metabolites which are believed to be responsible for the observed effects in this study. The phytochemical results matched with previous research findings [ 12 ]. Other researchers have further identified compounds such as transtetradecenoic acid, cishexadecenoic acid, transoctadecadecenol, oleic acid, palmitic acid, margaric acid, and stearic acid in the secondary metabolites of LTE using GC-MS analysis [ 16 ].

Catechin, caffeic acid, ellagic acid, quercetin and rutin have also been identified in LTE [ 46 ]. Streptozotocin, a known cytotoxic antibiotic with diabetogenic properties, is a glucose derivative that is selectively transported to pancreatic β-cells by GLUT-2 transporters [ 45 ].

In addition to alkylating and fragmenting DNA, STZ also generates reactive oxygen species ROS and nitric oxide and suppresses the activity of the enzyme aconitase [ 28 ]. On the other hand, Nicotinamide is a water-soluble B-vitamin with antioxidant and neuroprotective effects that offers partial protection to β-cells [ 28 ].

A general reduction in blood glucose was noted following the administration of the different doses of LTE. The findings also revealed that LTE possesses anti-hyperglycemic potentials, as observed in the oral glucose tolerance test.

These findings supported that of Gbadamosi et al. Again, using relatively lower doses of LTE in type-1 diabetic rats, Kuyoro et al. However, Isehunwa et al. Anti-diabetic medications regulate blood glucose levels through various mechanisms [ 31 ].

The reduction in blood glucose levels seen in the rats given LTE might have happened via a single or multiple processes, including facilitation of insulin secretion, obstruction of intestinal glucose absorption, and inhibition of hepatic gluconeogenesis, among others. Several investigators have reported that certain plant medicines containing polyphenols improve insulin release [ 9 , 11 , 46 ].

As a result, the polyphenol phytochemicals in LTE, like glibenclamide a long-acting sulfonylurea and an insulin secretagogue , may have worked on the residual β-cells to release insulin, facilitating glucose absorption [ 48 ].

Again, LTE and metformin were proven to lower fasting blood glucose levels. LTE phytoconstituents like flavonoids and tannins, as reported in other studies [ 9 ], may also have functioned similarly to metformin to lower glycemia by boosting peripheral glucose utilization [ 49 ].

Diabetes and cardiovascular diseases are strongly linked to dyslipidemia [ 27 ]. Other studies have found that type-2 diabetics have a high prevalence of abnormalities in plasma lipids such as total cholesterol TC , triglycerides TG , high-density lipoprotein cholesterols HDL-C , and low-density lipoprotein cholesterols LDL-C [ 50 ].

Alterations in serum lipids were noted following diabetes induction, which is consistent with earlier studies that diabetes promotes dyslipidemia [ 27 ]. The pathogenesis of diabetes has been strongly linked to the production of free fatty acids and low-grade inflammatory reactions as a result of dyslipidemia [ 51 ].

The improvements in lipid indices seen in the LTE-treated groups are comparable to what has previously been reported by Koukoui et al. Diabetes-related hepatic anomalies such as fatty liver disease, hepatic cirrhosis, and hepatocellular carcinomas [ 52 ] as well as STZ-induced liver damages [ 53 ] manifest as elevations in levels of liver enzymes such as AST, ALT, and ALP [ 52 , 53 ].

These increments, as noted in this study, were attenuated with LTE administration. In addition, unlike the liver and kidney, the pancreas sizes shrank in the diabetic rats as has been found in certain people with type-2 diabetes [ 54 ].

Streptozotocin STZ is known to cause inflammatory reactions, lipid peroxidation, and severe antioxidant depletion in the Islet of Langerhans, which leads to apoptosis and necrosis [ 55 , 56 ]. These findings are congruent with those shown in the photomicrographs of the pancreas from untreated diabetic rats, which showed severe pathological alterations in the Islet of Langerhans.

LTE was able to moderate these developments. The observed beneficial qualities may be attributed to its antioxidant properties [ 17 ]. This is also consistent with recent findings that reducing oxidative stress enhances β-cell function regeneration [ 57 ].

Substantial weight loss was observed in all the diabetic rats. Even though weight loss was reversed in all treatment groups, the reversal was statistically significant only in diabetic rats fed with glibenclamide. This finding is consistent with previous studies, as glibenclamide has been linked to weight gain [ 48 ].

Organ enlargements hypertrophies were noted in the livers and kidneys of the diabetic rats relative to their body weights. Similarly, renal hypertrophy, which may be irreversible, is linked to diabetes [ 59 ].

The reduction in liver-to-body weight ratio and kidney-to-body weight ratio in the LTE treated groups suggests that the extract may be useful in the management of complications associated with diabetes, such as hepatomegaly and renal hypertrophy [ 52 , 59 ].

Hepatic gluconeogenesis, which is increased in type-2 diabetes, tends to aggravate the disease [ 14 ]. Gluconeogenesis is mediated by enzymes such as pyruvate carboxylase, phosphoenolpyruvate PEP carboxykinase, fructose-1,6-bisphosphatase, and glucosephosphatase [ 60 ]. The extracts decreased hepatic glucose synthesis, although in a concentration-independent manner.

Phytochemicals like glycosides and triterpenes [ 9 ] in LTE, like metformin, may have activated the AMP Kinase, causing a switch from lipogenesis and gluconeogenesis to lipid oxidation and glucose absorption by muscle and liver cells [ 61 ].

In addition, LTE, like metformin, may have suppressed cAMP accumulation and hence lowered adenylate cyclase activity [ 9 , 62 ].

While it is still unclear which of the phytoconstituents in this study were responsible for the anti-diabetic effects of LTE in the intestines, some investigators have reported on the ability of some flavonoids to inhibit the actions of glucose transporters, GLUT-2 and SGLT-1 [ 63 , 64 ].

The LTE-mediated inhibition of glucose absorption by the whole intestines in-vivo and intestinal sacs ex-vivo may therefore have been similar to that of metformin, which is known to be deposited many folds into the brush borders of the intestines rather than plasma [ 65 ] and thus interferes with the actions of glucose transporters SGLT-1 and GLUT-2 to reduce blood glucose spikes [ 66 ].

Furthermore, Adinortey et al. The similarities in results obtained using both the whole intestines and intestinal sacs suggest that the intestinal sac method may be a useful model for high throughput rapid screening of phytomedicines that may inhibit intestinal glucose absorption.

Furthermore, the similarities suggest that the phytoconstituents in LTE may not be prodrugs, which require bioactivation to exert their pharmacological effects. The extract lowered FBG levels and also suppressed hyperglycemia during the oral glucose tolerance test.

LTE inhibited hepatic gluconeogenesis and suppressed intestinal glucose absorption. It also positively modulated levels of plasma lipids and liver enzymes. Although it did not improve body weight considerably, it reversed STZ-induced liver, kidney, and pancreatic damage and restored the morphology of the pancreatic Islet of Langerhans.

These findings suggest that the ethanolic leaf extract of Launaea taraxacifolia has blood glucose-lowering properties achieved through multiple processes. LTE may therefore be beneficial in the management of diabetes. Future studies would consider a bioassay-guided fractionation to isolate and investigate the compounds responsible for the observed anti-diabetic and anti-lipidemic effects.

The specific targets, enzymes and stages of gluconeogenesis and intestinal glucose transport interfered with by phytochemicals at the molecular level would also be investigated.

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Clinical Phytoscience volume Allergen-free environmentArticle Anti-diabetic properties 19 Allergen-free environment this article. Metrics Anti-siabetic. Diabetes Mellitus DM is a major health Thermogenic fat burner reviews, with a ;roperties prevalence of 9. Despite the availability of the classic anti-diabetic medications, many patients have not benefited from them due to their poor glycemic controls, high costs, inability to halt disease progression, and untoward side effects. Some patients thus resort to plant-based medicines such as those obtained from L. taraxacifolia etc.