Investigation of medicinal plants from Madagascar against DPP-IV linked to type 2 diabetes
TL;DR: In this paper, high-resolution DPP-IV inhibition profiling was employed for identification of active peaks, and Antidesma madagascariense was identified as DPPIV inhibitor, with an IC50 value of 3.9 ± 0.5μM.
About: This article is published in South African Journal of Botany.The article was published on 2018-03-01 and is currently open access. It has received 14 citations till now. The article focuses on the topics: Amentoflavone & Medicinal plants.
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TL;DR: The Juniperus species value as a source of secondary metabolites with relevant pharmaceutical potential is demonstrated, withAntitumor activity is by far the most studied, being followed by antibacterial and antiviral activities.
Abstract: Background: Plants and their derived natural compounds possess various biological and therapeutic properties, which turns them into an increasing topic of interest and research. Juniperus genus is diverse in species, with several traditional medicines reported, and rich in natural compounds with potential for development of new drugs. Methods: The research for this review were based in the Scopus and Web of Science databases using terms combining Juniperus, secondary metabolites names, and biological activities. This is not an exhaustive review of Juniperus compounds with biological activities, but rather a critical selection taking into account the following criteria: (i) studies involving the most recent methodologies for quantitative evaluation of biological activities; and (ii) the compounds with the highest number of studies published in the last four years. Results: From Juniperus species, several diterpenes, flavonoids, and one lignan were emphasized taking into account their level of activity against several targets. Antitumor activity is by far the most studied, being followed by antibacterial and antiviral activities. Deoxypodophyllotoxin and one dehydroabietic acid derivative appears to be the most promising lead compounds. Conclusions: This review demonstrates the Juniperus species value as a source of secondary metabolites with relevant pharmaceutical potential.
23 citations
Cites background from "Investigation of medicinal plants f..."
...5 μM, was recognized as a potential DPP-IV inhibitor [99]....
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TL;DR: The oral micelles of P(NVP-MGAM)/AF may become one of the most potent drugs in the treatment of diabetes mellitus, which opens up a new way for the prevention and treatment of Diabetes mellitus.
Abstract: In order to increase the oral bioavailability and antidiabetic effect of amentoflavone with multimechanisms, an oral micelle system was developed by using a N-vinyl pyrrolidone-maleate-guerbet alcohol monoester polymer for the first time, which was designated as P(NVP-MGAM)/AF. After oral administration, P(NVP-MGAM)/AF enhanced the oral bioavailability of amentoflavone, which was approximately 3.2 times that of amentoflavone solution. The animal study using the KKAy insulin-resistant diabetes mouse model indicated that it regulates the expression and activity of downstream signaling factors and proteins by lowering blood lipids, reducing inflammatory responses and activating the peroxisome proliferator-activated receptor (PPAR) γ signaling pathway and PI3K/Akt signaling pathway. After being made into micelles, it is more effective because of its better absorbability and bioavailability. The results from this study provide a theoretical basis for the clinical application of amentoflavone for diabetes treatment. The oral micelles of P(NVP-MGAM)/AF may become one of the most potent drugs in the treatment of diabetes mellitus, which opens up a new way for the prevention and treatment of diabetes.
20 citations
13 Apr 2012
TL;DR: The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials.
Abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials.
14 citations
TL;DR: The results of high-performance liquid chromatography analysis showed that penta-O-galloyl-β-D-glycopyranose was one of the main compounds in both fruit and leaf extracts, and it may be considered that R. coriaria fruit and Leaf extracts can be standardized on this substance and used in the development of both medicinal products and functional food for diabetes.
Abstract: The leaves and fruits of Rhus coriaria are traditionally used in Turkey for the treatment of diabetes. The aim of the present study is to determine α-amylase, α-glucosidase, and pancreatic lipase inhibitory activities of R. coriaria leaf and fruit ethanol extracts (80%), and to isolate active compounds against these enzymes. As a result of the activity-guided isolation, the active compounds were determined as the amentoflavone, agathisflavone, and 1,2,3,4,6-penta-O-galloyl-β-glucopyranose. Agathisflavone, amentoflavone, and penta-O-galloyl-β-glucopyranose inhibited α-glucosidase with 11.4 ± 0.9, 11.3 ± 0.7, and 4.1 ± 0.1 µM IC50 values, respectively. Furthermore, penta-O-galloyl-β-glucopyranose inhibited α-amylase with 6.32 ± 0.18 µM IC50 . These three compounds also significantly inhibited (P < 0.05) pancreatic lipase. The results of high-performance liquid chromatography analysis showed that penta-O-galloyl-β-D-glycopyranose was one of the main compounds in both fruit and leaf extracts. Therefore, it may be considered that R. coriaria fruit and leaf extracts can be standardized on this substance and used in the development of both medicinal products and functional food for diabetes. PRACTICAL APPLICATION: Rhus coriaria (Sumac) is one of the plants that is well known and used around the world as a spice. It is also used against diabetes traditionally. The determination of effective compounds can lead to the standardization and development of both medicinal products and functional foods for diabetes. While the fruits of the plant are used as a spice all around the world, the leaves are generally throw away; therefore, the usage of the leaves to the food and medical industry can lead to beneficial effects on the economy.
13 citations
27 Nov 2020
TL;DR: The aim of the experiment is to evaluate the in vitro antidiabetic activity and in-silico studies of the binding energies of Palmatine, acarbose, and Sitagliptin with the three enzymes of alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-IV).
Abstract: Palmatine a protoberberine alkaloid has been previously reported to possess in vivo antidiabetic and antioxidant property. The aim of the experiment is to evaluate the in vitro antidiabetic activity and in-silico studies of the binding energies of Palmatine, acarbose, and Sitagliptin with the three enzymes of alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-IV). The in vitro antidiabetic study was done by evaluating the inhibitory effect of palmatine on the activities of alpha-amylase, alpha-glucosidase, and DPP-IV. Acarbose, and sitagliptin was used as standard drug. The molecular docking study was performed to study the binding interactions of palmatine with alpha-glucosidase, a-amylase, and DPP-IV. The binding interactions were compared with the standard compounds Sitagliptin and acarbose. Palmatine with IC50 (1.31 ± 0.27 μM) showed significant difference of (< 0.0001) higher inhibiting effect on alpha-amylase and weak inhibiting effect on alpha-glucosidase enzyme with IC50 (9.39 ± 0.27 μM) and DPP-IV with IC50 (8.7 ± 1.82 μM). Palmatine possess inhibition effect on the three enzymes.
11 citations
Cites background or result from "Investigation of medicinal plants f..."
...A study has shown that Berberine which is an alkaloid have potency to inhibit the DPP-IV enzyme, but activity was lower compared to sitagliptin (Beidokhti et al. 2018). which was in accordance with DPP-IV inhibiting activity of palmatine observed in our study....
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...A study has shown that Berberine which is an alkaloid have potency to inhibit the DPP-IV enzyme, but activity was lower compared to sitagliptin (Beidokhti et al. 2018)....
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References
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TL;DR: Clinical trials with the incretin mimetic exenatide and liraglutide show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) associated with weight loss, but long-term clinical studies are needed to determine the benefits of targeting the inc retin axis for the treatment of type 2 diabetes.
3,497 citations
TL;DR: It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding.
Abstract: Diabetes is a group of chronic diseases characterized by hyperglycemia. Modern medical care uses a vast array of lifestyle and pharmaceutical interventions aimed at preventing and controlling hyperglycemia. In addition to ensuring the adequate delivery of glucose to the tissues of the body, treatment of diabetes attempts to decrease the likelihood that the tissues of the body are harmed by hyperglycemia.
The importance of protecting the body from hyperglycemia cannot be overstated; the direct and indirect effects on the human vascular tree are the major source of morbidity and mortality in both type 1 and type 2 diabetes. Generally, the injurious effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy). It is important for physicians to understand the relationship between diabetes and vascular disease because the prevalence of diabetes continues to increase in the United States, and the clinical armamentarium for primary and secondary prevention of these complications is also expanding.
### Diabetic retinopathy
Diabetic retinopathy may be the most common microvascular complication of diabetes. It is responsible for ∼ 10,000 new cases of blindness every year in the United States alone.1 The risk of developing diabetic retinopathy or other microvascular complications of diabetes depends on both the duration and the severity of hyperglycemia. Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both severity of hyperglycemia and presence of hypertension in the U.K. Prospective Diabetes Study (UKPDS), and most patients with type 1 diabetes develop evidence of retinopathy within 20 years of diagnosis.2,3 Retinopathy may begin to develop as early as 7 years before the diagnosis of diabetes in patients with type 2 diabetes.1 There are several proposed pathological mechanisms by which diabetes may lead …
1,812 citations
TL;DR: A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes and MK-0431, the phosphate salt of compound 1, was selected for development.
Abstract: A novel series of β-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC50 = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.
823 citations
TL;DR: In a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA1c [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks as discussed by the authors.
Abstract: OBJECTIVE —To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS —In a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA1c [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks.
RESULTS —Sitagliptin 100 and 200 mg produced significant ( P < 0.001) placebo-subtracted reductions in A1C (−0.79 and −0.94%, respectively) and fasting plasma glucose (−1.0 mmol/l [−17.1 mg/dl] and −1.2 mmol/l [−21.3 mg/dl], respectively). Patients with baseline A1C ≥9% had greater reductions in placebo-subtracted A1C with sitagliptin 100 and 200 mg (−1.52 and −1.50%, respectively) than those with baseline A1C <8% (−0.57 and −0.65%) or ≥8 to <9.0% (−0.80 and −1.13%, respectively). In a meal tolerance test, sitagliptin 100 and 200 mg significantly decreased 2-h postprandial glucose (PPG) (placebo-subtracted PPG −2.6 mmol/l [−46.7 mg/dl] and −3.0 mmol/l [−54.1 mg/dl], respectively). Results for the above key efficacy parameters were not significantly different between sitagliptin doses. Homeostasis model assessment of β-cell function and proinsulin-to-insulin ratio improved with sitagliptin. The incidence of hypoglycemia was similar, and overall gastrointestinal adverse experiences were slightly higher with sitagliptin. No meaningful body weight changes from baseline were observed with sitagliptin 100 (−0.2 kg) or 200 mg (−0.1 kg). The body weight change with placebo (−1.1 kg) was significantly ( P < 0.01) different from that observed with sitagliptin.
CONCLUSIONS —In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states, improved measures of β-cell function, and was well tolerated in patients with type 2 diabetes.
794 citations
TL;DR: The results suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing excellent oral bioavailability and potent antihyperglycemic activity with potential for once-a-day administration.
Abstract: Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine (NVP-DPP728, 8c) to its follow-up, 1-[[(3-hydroxy-1-adamantyl) amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP-LAF237, 12j). The pharmacological profile of 12j in obese Zucker fa/fa rats along with pharmacokinetic profile comparison of 8c and 12j in normal cynomolgus monkeys is discussed. The results suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing excellent oral bioavailability and potent antihyperglycemic activity with potential for once-a-day administration.
693 citations