Antidiabetic Potential of Novel 1,3,5-Trisubstituted-2-Thioxoimidazloidin-4-One Analogues: Insights into α-Glucosidase, α-Amylase, and Antioxidant Activities.

As the ninth leading cause of death globally, diabetes mellitus (DM) is considered to be the worst chronic metabolic disease requiring an enormous need for healthcare with over 578 million expected cases by 2023. Several recent findings have demonstrated that mediating the activity of carbohydrate-hydrolyzing enzymes, including α-amylase and α-glucosidase, could be a potential strategy for managing the development of DM. In the presented study, a novel set of 1,3,5-trisubstituted-2-thioxoimidazolidin-4-ones was designed, synthesized, and characterized. The antidiabetic activity of the synthesized compounds was explored by assessing their inhibitory activity toward α-amylase and α-glucosidase enzymes. The results demonstrated that this class of compounds exhibits considerable inhibitory activity toward both α-amylase and α-glucosidase enzymes. Among the synthesized compounds, compound 5a demonstrated the most inhibitory activity with IC50 of 5.08 and µg/mL and 0.21 µg/mL toward α-glucosidase and α-amylase activities, respectively, as compared to the drug Acarbose (IC50 = 5.76 µg/mL and 0.39 µg/mL, respectively). To gain insights into the antidiabetic potential of compound 5a, we assessed the cytotoxic and antioxidant activities. Our findings indicated that compound 5a displays considerable cytotoxicity toward WI-38 cells with an IC50 of 88.54 µg/mL, as compared to the drug Celecoxib (IC50 = 93.05 µg/mL). Further, compound 5a exhibited a high scavenging activity toward 2,2-Diphenyl1-picrylhydrazyl (DPPH) free radicals (IC50 = 51.75 µg/mL) and showed a low potential to produce ROS as indicated by the monitoring of the generated H2O2 (132.4 pg/mL), as compared to Trolox (IC50 = 58.09 µg/mL) and Celecoxib (171.6 pg/mL). Finally, we performed extensive molecular modeling studies to affirm the binding affinity of this class of compounds to the binding pocket of α-amylase and α-glucosidase enzymes. Collectively, our findings indicate that this class of compounds, particularly compound 5a, could be utilized as a lead structure for the development of novel compounds with potential antidiabetic and antioxidant activities.

Biochemical and Molecular Mechanisms of Platelet-Rich Plasma in Ameliorating Liver Fibrosis Induced by Dimethylnitrosurea.

BACKGROUND/AIMS: Hepatic fibrosis is a wound-healing process in the chronically injured liver. Clinical application of platelet-rich plasma (PRP) is of considerable interest for wound healing and regeneration. In view of the regeneration effect of PRP, we designed this study to explore the hypothesis that PRP could play a role in improving the biochemical and molecular changes that occur in liver fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Four groups were studied: control, PRP control, DMN (liver fibrosis), and DMN+PRP groups. Serum liver enzymes (alanine amino transferase ALT, aspartate amino transferase AST, gamma glutamyl transferase GGT, and lactate dehydrogenase LDH), and liver hydroxyproline content were measured colorimetrically.Interleukin-8 (IL-8) and B-cell lymphoma (Bcl2) were determined by enzyme-linked immunosorbent assay. And the expression levels of alpha-smooth muscle actin (α-SMA) ,transforming growth factor (TGF-ß), and nuclear factor kappa B1(NF-қB1) were evaluated by quantitative real-time polymerase chain reaction. RESULTS: Our results showed that PRP markedly improved the DMN-induced changes in liver enzymes accompanied by a significant decrease in liver hydroxyproline content and IL-8 level induced by DMN, and an increase in the anti-apoptotic marker Bcl-2. PRP also showed significant down-regulation of fibrosis-related genes α-SMA and TGF-ß and a significant decrease in the inflammatory marker NF-қB1. CONCLUSION: Based on these encouraging results, we consider that PRP could be a promising new agent for liver regeneration and alleviation of fibrosis.

Potential impact of Panax ginseng against ethanol induced hyperlipidemia and cardiac damage in rats.

The objective of the current work was to explore the possible hypolipidemic and therapeutic impacts of Panax ginseng against cardiac damage in response to ethanol ingestion in male and female rats. 10% ethanol was ingested (2ml/Kg) to both male and female rats daily for fourteen days. The results showed that ingestion of ginseng (150mg/Kg) daily for six weeks to male and female rats intoxicated with ethanol, two weeks after ethanol ingestion, successfully modulated the alterations in the serum lipid profiles, namely, triglycerides (TGs), total cholesterol (TCh), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C), in male and female rats exposed to ethanol versus untreated intoxicated ones. The plant also pronouncedly attenuated the increases in serum cardiac damage biomarkers, namely lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) compared with ethanol intoxicated untreated rats. In conclusion, this study showed that Panax ginseng has a beneficial impact against ethanol induced hyperlipidemia as a risk element for cardiovascular illness.

Production of Inulinase by Free and Immobilized Cells of Penicillium funiculosum p.36

The aim of this work was to optimize the growth conditions and continuous production of the enzyme using free and immobilized cells of inulinase by Penicillium funiculosum. The highest yield of enzyme (163.5U/mL) was obtained when the culture was incubated at 27oC and 200 rpm for 96h in a fermentation medium containing both inulin and peptone as sole carbon and nitrogen source, respectively. When the cells of the P. funiculosum were immobilized on different carriers, especially linen fibers, their production ability was successfully maintained for seven successive batches. When the fermentation was carried out using inulin juice prepared from Jerusalem artichoke tubers (in place of pure inulin), inulinase production could be sustained till the second cultivation batch of the P. funiculosum immobilized on linen fibers, yielding 122 U/mL enzyme. Results proved the feasibility of using crude inulin juice as a simple and economic carbon source for the production of inulinase.

Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats

The present study examined the effect of water extract (200 mg/kg body weight) of Rosmarinus officinalis L. in streptozotocin (STZ)-induced diabetic rats for 21 days. The hepatoprotective effects were investigated in the liver tissues sections. There was a significant increase in serum liver biochemical parameters (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase), accompanied by a significant decrease in the level of total protein and albumin in the STZ-induced rats when compared with that of the normal group. The high-dose treatment group (200 mg/kg body wt) significantly restored the elevated liver function enzymes near to normal. This study revealed that rosemary extracts exerted a hepatoprotective effect. The results indicate that the extract exhibits the protective effect on tissues and prove its potentials as an antidiabetic agent (AU)

Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats.

The present study examined the effect of water extract (200 mg/kg body weight) of Rosmarinus officinalis L. in streptozotocin (STZ)-induced diabetic rats for 21 days. The hepatoprotective effects were investigated in the liver tissues sections. There was a significant increase in serum liver biochemical parameters (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase), accompanied by a significant decrease in the level of total protein and albumin in the STZ-induced rats when compared with that of the normal group. The high-dose treatment group (200 mg/kg body wt) significantly restored the elevated liver function enzymes near to normal. This study revealed that rosemary extracts exerted a hepatoprotective effect. The results indicate that the extract exhibits the protective effect on tissues and prove its potentials as an antidiabetic agent.