Journal Article•
Dipeptidyl peptidase-iv inhibitory activity of some indonesian medicinal plants
01 Mar 2016-Asian Journal of Pharmaceutical and Clinical Research (Asian Journal of Pharmaceutical and Clinical Research)-Vol. 9, Iss: 2, pp 375-377
TL;DR: About 5 of 20 ethanol extracts showed the ability to inhibit DPP-IV activity in vitro at a concentration of 2.5 ug/ml, and the fenugreek seed showed the highest inhibition to D PP-IV.
Abstract: Objective: The focus of this research is to determine the inhibitory activity of ethanol extracts from 20 plants that have been used traditionally in Indonesia for the treatment of diabetes for dipeptidyl peptidase-IV (DPP-IV) inhibitory activity. Methods: A crude drug was extracted by reflux methods using 96% ethanol for 1 hr. The assay was performed with modification methods of Al Masri et al. using 96 micro well plates, and the absorbance was measured at 380 nm using the microplate reader. Sitagliptin was used as a standard inhibitor DPP-IV. Results: About 5 of 20 ethanol extracts showed the ability to inhibit DPP-IV activity in vitro at a concentration of 2.5 ug/ml. The active extract was obtained from pomegranates rind, bungur leaves, brotowali stem, bodhi leaves, and fenugreek seeds. The inhibitory percentage of the fifth extract was 58.79±2.23, 60.22±2.01, 65.86±0.02, 68.98±1.95, and 71.29±0.33. The IC50 value of sitagliptin was 1.104 ug/ml. Conclusion: The results of in vitro assay showed that some extract inhibited DPP-IV. The fenugreek seed showed the highest inhibition to DPP-IV. Keywords: Dipeptidyl peptidase-IV, Dipeptidyl peptidase-IV inhibitory, Fenugreek seed, Sitagliptin.
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TL;DR: The most extensive survey dealing with the ethnomedicinal knowledge of Thai medicinal plants utilized on diabetes management is delivered, and it is certain that the current review will spark further research on Thai plants for the development of new standardized phytomedicines through drug discovery programmes.
32 citations
TL;DR: In this article, a review of DPP-IV inhibitors and their mechanism of inhibition, activities of those isolated from various natural sources, and their capacity to overcome oxidative stress in disease conditions is presented.
Abstract: Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia that is predominantly caused by insulin resistance or impaired insulin secretion, along with disturbances in carbohydrate, fat and protein metabolism. Various therapeutic approaches have been used to treat diabetes, including improvement of insulin sensitivity, inhibition of gluconeogenesis, and decreasing glucose absorption from the intestines. Recently, a novel approach has emerged using dipeptidyl peptidase-IV (DPP-IV) inhibitors as a possible agent for the treatment of T2DM without producing any side effects, such as hypoglycemia and exhaustion of pancreatic β-cells. DPP-IV inhibitors improve hyperglycemic conditions by stabilizing the postprandial level of gut hormones such as glucagon-like peptide-1, and glucose-dependent insulinotropic polypeptides, which function as incretins to help upregulate insulin secretion and β-cell mass. In this review, we summarized DPP-IV inhibitors and their mechanism of inhibition, activities of those isolated from various natural sources, and their capacity to overcome oxidative stress in disease conditions.
21 citations
TL;DR: Caesalpinia sappan ethanol extract has a potential effect as a better antidiabetic agent than other extracts used in this study.
16 citations
TL;DR: In this article, Dietary polyphenols with great antidiabetic effects are the most abundant components in edible products and have attracted attention as dipeptidyl peptidyl enzyme-IV (DPP-IV) inhibitors.
Abstract: Dietary polyphenols with great antidiabetic effects are the most abundant components in edible products. Dietary polyphenols have attracted attention as dipeptidyl peptidase-IV (DPP-IV) inhibitors ...
13 citations
TL;DR: It has been shown that neem can control hyperglycemia and hypertension through over-expression of transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) and anti-oxidant effects andAnti-oxids play an important role in protective mechanisms of neem against metabolic syndrome and its complications.
Abstract: Metabolic syndrome is a condition associated with obesity, diabetes, dyslipidemia, and high blood pressure. Recently, the use of phytochemicals is suggested in the control and treatment of metabolic syndrome. The Azadirachta indica (neem) is an evergreen tree belonging to the family of Meliaceae. Multiple studies have been confirmed the anti-diabetic and anti-hypertension, anti-hyperlipidemia, and anti-obesity effects of neem. In this review, we reported the protective effects of neem against the complications of metabolic syndrome with a special focus on mechanisms that are involved. It has been shown that neem can control hyperglycemia and hypertension through over-expression of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and anti-oxidant effects. Neem also reduced the glucose uptake through up-regulation of glucose transporter 4 (GLUT4) and inhibition of key intestinal enzymes such as glucosidases. Moreover, neem showed anti-hypertensive effects possibility via the block of calcium channels, up-regulation of endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway. Anti-oxidant effects play an important role in protective mechanisms of neem against metabolic syndrome and its complications.
10 citations
Cites background or methods from "Dipeptidyl peptidase-iv inhibitory ..."
...Inhibition of DPP-IV (a peptidase) is a method for diabetes treatment (86)....
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...In this method, substrate Gly-Pro-p-Nitroanilide (GPPN) was cleaved to paranitroanilide (a yellow-colored product) by DPP-IV and the absorbance was measured at 380 nm. Inhibitory activity of neem leaves (35 μl with varying concentrations) was determined on DPP-IV activity via this method, and neem exhibited a weak inhibitory activity (17...
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...The use of the neem is most popular to control diabetes in different regions of the world, such as India (79), Pakistan (80), Bengal (81), Indonesia (82), and Northwest Nigeria (83)....
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...%) on DPP-IV (82)....
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...Inhibitory activity of neem leaves (35 μl with varying concentrations) was determined on DPP-IV activity via this method, and neem exhibited a weak inhibitory activity (17%) on DPP-IV (82)....
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References
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TL;DR: It is suggested that dipeptidyl peptidase-IV is the primary mechanism for GLP-1 degradation in human plasma in vitro and may have a role in inactivating the peptide in vivo.
Abstract: The metabolism of glucagon-like peptide-1 (GLP-1) has not been studied in detail, but it is known to be rapidly cleared from the circulation. Measurement by RIA is hampered by the fact that most antisera are side-viewing or C-terminally directed, and recognize both intact GLP-1 and biologically inactive. N-terminally truncated fragments. Using high pressure liquid chromatography in combination with RIAs, methodology allowing specific determination of both intact GLP-1 and its metabolites was developed. Human plasma was shown to degrade GLP-1-(7-36)amide, forming an N-terminally truncated peptide with a t1/2 of 20.4 +/- 1.4 min at 37 C (n = 6). This was unaffected by EDTA or aprotinin. Inhibitors of dipeptidyl peptidase-IV or low temperature (4 C) completely prevented formation of the metabolite, which was confirmed to be GLP-1-(9-36)amide by mass spectrometry and sequence analysis. High pressure liquid chromatography revealed the concentration of GLP-1-(9-36)amide to be 53.5 +/- 13.7% of the concentration of endogenous intact GLP-1 in the fasted state, which increased to 130.8 +/- 10.0% (P < 0.01; n = 6) 1 h postprandially. Metabolism at the C-terminus was not observed. This study suggests that dipeptidyl peptidase-IV is the primary mechanism for GLP-1 degradation in human plasma in vitro and may have a role in inactivating the peptide in vivo.
820 citations
"Dipeptidyl peptidase-iv inhibitory ..." refers background in this paper
...The development of antidiabetic that works by activating the GLP-1 was having problems, because GLP-1 is very rapidly degraded and deactivated by the enzyme DPP-IV [4-6]....
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TL;DR: It is concluded that side effects of inhibition therapy are likely to be mild, and DPP-IV inhibition may be an effective supplement to diet and exercise treatment in attempts to prevent the deterioration of glucose metabolism associated with the Western lifestyle.
Abstract: The insulinotropic hormone, glucagon-like peptide 1 (GLP-1), which has been proposed as a new treatment for type 2 diabetes, is metabolized extremely rapidly by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP-IV), resulting in the formation of a metabolite, which may act as an antagonist at the GLP-1 receptor. Because of this, the effects of single injections of GLP-1 are short-lasting, and for full demonstration of its antidiabetogenic effects, continuous intravenous infusion is required. To exploit the therapeutic potential of GLP-1 clinically, we here propose the use of specific inhibitors of DPP-IV. We have demonstrated that the administration of such inhibitors may completely protect exogenous GLP-1 from DPP-IV-mediated degradation, thereby greatly enhancing its insulinotropic effect, and provided evidence that endogenous GLP-1 may be equally protected. Preliminary studies by others in glucose-intolerant experimental animals have shown that DPP-IV inhibition greatly ameliorates the condition. GLP-1 has multifaceted actions, which include stimulation of insulin gene expression, trophic effects on the beta-cells, inhibition of glucagon secretion, promotion of satiety, inhibition of food intake, and slowing of gastric emptying, all of which contribute to normalizing elevated glucose levels. Because of this, we predict that inhibition of DPP-IV, which will elevate the levels of active GLP-1 and reduce the levels of the antagonistic metabolite, may be useful to treat impaired glucose tolerance and perhaps prevent transition to type 2 diabetes. The actions of DPP-IV, other than degradation of GLP-1, particularly in the immune system are discussed, but it is concluded that side effects of inhibition therapy are likely to be mild. Thus, DPP-IV inhibition may be an effective supplement to diet and exercise treatment in attempts to prevent the deterioration of glucose metabolism associated with the Western lifestyle.
527 citations
TL;DR: Inhibitors of DP IV activity, or DP IV-resistant glucagon-like peptide analogues, may be alternative therapeutic approaches for treatment of human diseases.
493 citations
"Dipeptidyl peptidase-iv inhibitory ..." refers background in this paper
...Activation of the GLP-1 receptor will cause a reduction in glucagon secretion, inhibiting gastric emptying and induces a satiety [2,3]....
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TL;DR: In this paper, Na-Cbz-Gly-DL-Pro (2g) and 2-naphthylamine (1 g) were dissolved in 50 ml of tetrahydrofuran at -10 ~ C. This solution was added 1.35 g N,Nl-dicyclohexylcarbodiimide and with mechanical stirring the solution was brought slowly to 25 o C with stirring continued for 16 hours.
Abstract: Material and Methods Na-Cbz-Glycyl-DL-Prolyl-fi-Naphthylamide. Na-Cbz-Gly-DL-Pro (2g) and 2-naphthylamine (1 g) were dissolved in 50 ml of tetrahydrofuran at -10 ~ C. To this solution was added 1.35 g N,Nl-dicyclohexylcarbodiimide and with mechanical stirring the solution was brought slowly to 25 o C with stirring continued for 16 hours. The precipitated urea was removed by filtration and the filtrate evaporated to dryness in vacuo. The amorphous residue was extracted with dichloromethane and crystallization occurred on reduction of solvent in vacuo. Recrystallization was performed from dichloromethane on the addition of 60 ~ ligroin and refrigeration. m.p. 142--1430 C. Calculation for CesHesN80 ~ (m.w. 431.53): C, 69.60; H, 5.85; N, 9.73. Found: C, 69.83; H, 5.74; N, 9.59. Glycyl-DL-ProIyl-fl-Naphthylamide H B r . The N-protected compound was slowly dissolved in a small volume of glacial acetic acid saturated with hydrogen bromide containing a small quantity of phenol (GLENNER et al., 1965), and agitated for two hours during which time gas evolution ceased. Addition of ten-fold solvent excess of ethyl ether precipitated an amorphous material which was washed, and triturated with further additions of ether. The triturated residue was dissolved in a minimal quantity of methyl alcohol and crystallized on the addition of ether. Recrystallized from methyl alcohol. Browns, 2448 C; m.p. 253--254.5. Calculated for C17H19N302.HBr (m.w. 378.32): C, 53.97; H, 5.34; N, 11.11. Found: C, 53.98; H, 5.13; N, 11.10; ~'~ --119.9 (c, 1 in methanol). The quantitative assay methods as well as the preparative methods for fractionation of the enzymically active proteins have been described earlier (HorstT and GLEN~ER, 1964; HO~SU et al., 1966) and additional details are given in the text.
390 citations
TL;DR: Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin and a comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin.
Abstract: The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chen et al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG.
226 citations
"Dipeptidyl peptidase-iv inhibitory ..." refers background in this paper
...Tannin molecules contained in L. speciosa extract, known as Banaba extract an estimated charge of its activity as a stimulator Insulin-like Glucose Transport [19-21]....
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...speciosa extract, known as Banaba extract an estimated charge of its activity as a stimulator Insulin-like Glucose Transport [19-21]....
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