Synthesis, Characterization and Biological Evaluation of Thiazolidinedione Derivative as Novel Antidiabetic Agents

Thiazolidinedione derivative have Antihyperglycemic activity, they are agonists for the peroxisome proliferator-activated receptor (PPAR), which controls glucose synthesis, transport, and utilization via regulating the transcription of insulin-responsive genes. A number of novel insulin sensitizers are currently being researched. Several of these are derivatives of Thiazolidinedione, but others have different chemical structures. In this work, we created some new Thiazolidinedione derivative based on structure–activity relationship as closely as feasible. The Thiazolidine-2,4-Dione derivatives were manually developed and synthesized using the proper synthetic techniques, then tested in vitro for antihyperglycemic action using the Sucrose loading model (SLM) and the Alloxan induced diabetes model (AIDM). The newly synthesized Thiazolidine-2,4-Dione derivative was characterized using infrared (IR) and proton (H) nuclear magnetic resonance. In this study we found that Compound M-4 has a lot of antihyperglycemic action, thus it's a good idea to think about using it as a lead material for the creation of anti-diabetic drugs.

Proanthocyanidin B2 attenuates postprandial blood glucose and its inhibitory effect on alpha-glucosidase: analysis by kinetics, fluorescence spectroscopy, atomic force microscopy and molecular docking

As a dimer of proanthocyanidin, proanthocyanidin B2 (PB2) was found to effectively attenuate postprandial blood glucose in mice after sucrose loading.

Dynamics and Control of Phloem Loading of Indoleacetic Acid in Seedling Cotyledons of Ricinus Communis During Germination

During seed germination sugars and auxin are produced from stored precursors or conjugates respectively and transported to the seedling axis. To elucidate the mode of travel of IAA into the phloem a solution of [3H]indoleacetic acid (IAA), together with [14C]sucrose, was injected in the endosperm cavity harboring the cotyledons of germinating seedlings of Ricinus communis. Phloem exudate from the cut hypocotyl was collected and the radioactivity recorded. Sucrose loading in the phloem was inhibited at higher IAA levels, and the rate of filling of the transient pool(s) was reduced by IAA. IAA was detected within 10 minutes, with the concentration increasing over 30 min and reaching a steady-state by 60 min. The kinetics indicated that phloem loading of IAA involving both an active, carrier-based, and a passive, diffusion-based component, with IAA traveling along a pathway containing an intermediary pool, possibly the protoplasts of mesophyll cells. Phloem loading of IAA was altered by sucrose, K+ and a range of non-specific and IAA-specific analogues and inhibitors in a manner that showed that IAA moves into the phloem from the extra cotyledonary solution by multiple pathways, with a carrier mediated pathway playing a principal role.

Apple Pectin Affects the Efficacy of Epigallocatechin Gallate on Oral Sucrose Tolerance Test in Adult Mice

Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch® Ultra® blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice.

The Inhibition of Lipase and Glucosidase Activities by Acacia Polyphenol

Acacia polyphenol (AP) extracted from the bark of the black wattle tree (Acacia mearnsii) is rich in unique catechin-like flavan-3-ols, such as robinetinidol and fisetinidol. In anin vitrostudy, we measured the inhibitory activity of AP on lipase and glucosidase. In addition, we evaluated the effects of AP on absorption of orally administered olive oil, glucose, maltose, sucrose and starch solution in mice. We found that AP concentration-dependently inhibited the activity of lipase, maltase and sucrase with an IC50of 0.95, 0.22 and 0.60 mg ml−1, respectively. In ICR mice, olive oil was administered orally immediately after oral administration of AP solution, and plasma triglyceride concentration was measured. We found that AP significantly inhibited the rise in plasma triglyceride concentration after olive oil loading. AP also significantly inhibited the rise in plasma glucose concentration after maltose and sucrose loading, and this effect was more potent against maltose. AP also inhibited the rise in plasma glucose concentration after glucose loading and slightly inhibited it after starch loading. Our results suggest that AP inhibits lipase and glucosidase activities, which leads to a reduction in the intestinal absorption of lipids and carbohydrates.

The Effects of Corni Fructus Extract and Its Fractions Against α-Glucosidase Inhibitory Activitiesin Vitroand Sucrose Tolerance in Normal Rats

Corni Fructus (Cornus officinalis Sieb. et Zucc.) is a traditional medicine exerting multifaceted protective effects against diabetes and its complications. In this study, to further identify the physiological effects of Corni Fructus against diabetes and its complications, we investigated α-glucosidase inhibitory activities in vitro and employed the sucrose tolerance test as an indicator of the control of the postprandial blood glucose level. In vitro assays showed that Corni Fructus extract has a higher inhibitory activity than its major components. Then, Corni Fructus extract was fractionated again to screen the fractions showing a strong inhibitory activity against α-glucosidase. Of the tested fractions, five showed a rate of α-glucosidase inhibition of over 80%. Next, the four abundant fractions were evaluated their IC50values, as well as the inhibition mode in vitro and plasma glucose level after sucrose loading in normal Wistar rats. As a result, the IC50values of these fractions were between 1.1–2.1 μg/ml. Among the four fractions, three showed mixed inhibition, while one (Fr. 4–9) showed the competition-independent inhibition of α-glucosidase. In addition, Fr. 4S-1 significantly inhibited the rise in the plasma glucose levels at a dose of 20 mg/kg body weight after sucrose loading. These results indicate that Fr. 4S-1 from Corni Fructus has a potential to control postprandial hyperglycemia by α-glucosidase inhibition.