ABSTRACT
The present study aimed to screen the Rhazya stricta Decne root for its antihyperglycemic and antioxidants potential through invitro assays along with phytochemical and elemental analyses. The crude extract was prepared through maceration and fractionated using solvent-solvent extraction technique. The spectroscopic studies indicated the presence of various phytochemical classes in the extract and its fractions. The antioxidant assays showed notable results along with a good concentration of phenolic and flavonoid contents. Enzyme inhibition assays demonstrated glucose-lowering effects by inhibiting the enzyme activity which could reduce post-prandial blood glucose level. The Dipeptidyl peptidase-IV (DPP-IV) inhibition assay results showed the novel DPP-IV inhibition activity of the plant extract and all fractions showed noteworthy enzyme inhibition and antihyperglycemic activity. Conclusively, the Rhazya stricta root extract displayed its antioxidant and antihyperglycemic potential due to the presence of various classes of phytochemicals and micro-nutrients.
El presente estudio tuvo como objetivo examinar la raíz de Rhazya stricta Decne por su potencial antihiperglicémico y antioxidante a través de ensayos in vitro junto con análisis fitoquímicos y elementales. El extracto crudo se preparó por maceración y se fraccionó usando una técnica de extracción solvente-solvente. Los estudios espectroscópicos indicaron la presencia de varias clases fitoquímicas en el extracto y sus fracciones. Los ensayos antioxidantes mostraron resultados notables junto con una importante concentración de contenido fenólico y flavonoide. Los ensayos de inhibición enzimática demostraron efectos reductores de la glucosa al inhibir la actividad enzimática que podría reducir el nivel de glucosa posprandial en sangre. Los resultados del ensayo de inhibición de Dipeptidyl peptidase-IV (DPP-IV) mostraron la nueva actividad de inhibición de DPP-IV del extracto de la planta y todas las fracciones mostraron una notable inhibición enzimática y actividad antihiperglicémica. En conclusión, el extracto de raíz de Rhazya stricta Decne mostró su potencial antioxidante y antihiperglicémico debido a la presencia de varias clases de fitoquímicos y micronutrientes.
Subject(s)
Plant Extracts/pharmacology , Apocynaceae/chemistry , Hypoglycemic Agents/pharmacology , Antioxidants/pharmacology , Phenols/analysis , Spectrophotometry, Ultraviolet , Flavonoids/analysis , Blood Glucose/drug effects , In Vitro Techniques , Plant Extracts/chemistry , Spectroscopy, Fourier Transform Infrared , Plant Roots/chemistry , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/antagonists & inhibitors , Phytochemicals , Hypoglycemic Agents/chemistry , Antioxidants/chemistryABSTRACT
@#By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.
ABSTRACT
Dipeptidyl peptidase IV (DPP IV) is relatively new anti-diabetic target. DPP IV inhibitors lower fasting andpostprandial glucose concentrations by preventing the degradation of the natural hypoglycemic incretin hormones:glucose-dependent insulinotropic peptide and glucagon-like peptide-1. In this work, the high throughput dockingsoftware FRED was used as a virtual screening tool against in house built drug database to discover new DPP IVinhibitors. One of the highest ranking hits, the antihistamine drug fexofenadine, was found to inhibit recombinanthuman DPP IV in vitro with IC50 = 4.6 (±1.0) µM. The anti-diabetic effect of fexofenadine was validated in vivo byoral glucose tolerance test. These results could be helpful in the development of novel DPP IV inhibitors based onfexofenadine scaffold for the treatment of type 2 diabetes.
ABSTRACT
Objective To explore the efficacy of saxagliptin in the treatment of failed glycemic control of patients with type 2 diabetes mellitus on the basis of established treatments.Methods 172 cases of failed glycemic control of patients with type 2 diabetes mellitus from June 2013 to December 2014 in department of endocrinology of the first hospital of Ningbo were selected and received health education of 8 weeks, then received saxagliptin on the basis of established treatments for a consecutive treatment of 12 weeks.The HbA1c, fasting blood glucose ( FBG), 2-hours postprandial blood glucose (2hPBG), body mass index (BMI), insulin dosage and adverse event were observed.Results The FBG,HbA1c and 2hPBG after treatment of 12 weeks were significantly lower than those pre-treatment[(7.1 ±2.0)vs.(8.3 ±1.6)mmol/L,(10.2 ±2.3)vs.(15.2 ±2.9)mmol/L,(7.0 ±1.5) vs.(8.0 ±1.7)%], with significant difference (all P <0.05), while there was no significant difference in BMI between pre-and post-treatment [(24.4 ±3.0)vs.(24.9 ±2.7)kg/m2].The insulin dose after treatment of 12 weeks was significantly lower than that pre-treatment[(22.6 ±7.9)vs. (32.3 ±8.2) U/d], with significant difference (P <0.05).There were two patients dropout because of the intolerable digestive tract symptom. Conclusion The adding of saxagliptin could control FBG,2hPBG and HbA1c effectively and decrease insulin dose, without gaining weight in the treatment of failed glycemic control of patients with type 2 diabetes mellitus on the basis of established treatments.
ABSTRACT
OBJECTIVE: To explore a new synthesis method of the saxagliptin intermediate of the dipeptidyl peptidase IV (DPP-IV)inhibitor saxagliptin, N-BOC-3-hydroxy-1-adamantylglycine, to reduce the synthesis cost of saxagliptin. METHODS: The synthesis used 1-adamantane carboxylic acid (1) as the starting material. Through achlorination, substitution, and decarboxylation afford 1-adamantyl methyl ketone (2) was obtained, which was then converted into 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (3)by oxidation with potassium permanganate in aqueous NaOH. Compound 3 reacted with hydroxylamine hydrochloride to give the 2-(3-hydrox-1-adamantyl)-2-hydroxyimino acetic acid(4), and then oxime 4 was reduced, and got the amino with BOC2O to afford dipeptidyl peptidase IV (DPP-IV)inhibitor saxagliptin intermediate N-BOC-3-hydroxyadamanty- lglycine(5). RESULTS: We got a new compound 4 which had not been reported. The 36% overall yield was reached. CONCLUSION: This synthetic route is simple, its reaction conditions are mild, and the raw materials are cheap and readily available, so it is suitable for manufacturing purposes.
ABSTRACT
Dipeptidyl peptidase (DPP)-IV inhibitors are a new approach to the treatment of type 2 diabetes. DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9. DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we conducted molecular docking studies on clinical inhibitors of DPP-IV.
ABSTRACT
To study the effect and mode of action of water extract (DVW) and polar fraction of ethanol extract (DVE-4) of D. viscosa in high-fructose diet induced insulin resistance in male Wistar rats. D. viscosa’s effects were evaluated on a battery of targets involved in glucose homeostasis (in vitro studies). Rats were rendered insulin resistant by feeding 66% (w/w) fructose and 1.1% (v/w) coconut oil mixed with normal pellet diet (NPD) for six weeks. DVW and DVE4 at different doses were administered simultaneously. At the end of the study, blood glucose, oral glucose tolerance test, lipid profile and insulin were estimated and homeostatic model assessment (HOMA) levels were calculated. In addition, enzymatic and non-enzymatic liver antioxidant levels were also estimated. Quantification of biomarker quercetin was done using HPLC. Fructose diet with DVW, DVE-4 significantly reduced blood glucose, serum insulin, HOMA, lipid profiles and significantly improved glucose tolerance and HDL-c levels. In addition, these extract and fraction also decreased oxidative stress by improving endogenous antioxidants. In different bioassays, DVW and DVE-4 inhibited protein tyrosine phosphatase-1B with IC50 65.8 and 54.9 g/ml respectively and showed partial inhibition of dipeptidyl peptidase-IV. Moreover, DVW and DVE-4, at 10 mg/ml showed 60 and 54.2% binding to peroxisome proliferator-activated receptor-g. Further, 2.1% (w/w) of quercetin was quantified in bioactive-DVE-4 using HPLC method. The results provide pharmacological evidence of D. viscosa in treatment of prediabetic conditions and these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.
ABSTRACT
Recent advances in understanding insulin secretion, action and signaling have led to the development of new pharmacological agents. Several new emerging drugs and drug classes for the management of diabetes are under development, including the incretin mimetic agents (exenatide, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 analogues), the amylin analogue pramlintide, the cannabinoid-1 receptor antagonist rimonabant, the mixed peroxisome proliferator-activated receptor agonists muraglitazar and the inhaled insulin preparation Exubera. New drugs and technologic advances being made available will help achieve the goals of treating patients with diabetes to all the appropriate metabolic targets. Longer term studies will help providers weigh the benefits, adverse effects, cost, and unknown long-term risks of these medications.