Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Papaya fruit by-products as novel food ingredients in cupcakes

Large quantities of waste generated from papaya fruit processing, especially seeds, can be recovered and combined to obtain added-value products. This investigation aimed to evaluate the physicochemical properties and antimicrobial activity of papaya seed powder (PSP) and papaya seed oil (PSO), and their applications as novel nontraditional food ingredients in cupcakes to promote them as high-value products. The GC–MS analysis for PSP revealed 39 compounds possess various biological activities, indicating the safety of its consumption. Papaya seeds are an excellent source of protein (27.95 %), oil (31.83 %), ash (7.86 %) and fibers (18.53 %). They have the potential to produce high-quality oleic oil with highly similar physicochemical properties and fatty acids profile as olive oil. The broad-spectrum inhibition of PSP and PSO against the tested pathogens proved their potential as natural antimicrobial agents. PSP can successfully be used (as nutritive ingredients and antimicrobial agents) in combination with wheat flour to obtain delicious and healthy nutritious chocolate cupcakes. The supplemented cupcakes (up to 15 % level) had improved quality attributes and enhanced nutritional value with respect to protein (16.89 %), ash (4.17 %) and fibers (3.28 %). PSP and PSO are safety, edible, nutritious, antimicrobial and can be processed into value-added products. They can be used as novel functional food ingredients or natural additives, providing added value to the food processing

Phytochemical Profile of the Ethanol Extract of <i>Malvaviscus arboreus</i> Red Flower and Investigation of the Antioxidant, Antimicrobial, and Cytotoxic Activities

Flowers are rich sources of bioactive antimicrobial, antioxidant, and anticancer components. This study aimed to determine the constituents of the ethanol extract of Malvaviscus arboreus red flower (ERF) by GC-MS analysis and HPLC identification of phenolic compounds and flavonoids, in addition to the 1HNMR fingerprint. The antimicrobial, antioxidant, and cytotoxic activities of the ERF were investigated. The GC-MS analysis revealed twenty-one components, while HPLC analysis revealed the presence of phenolic and flavonoid compounds. The ERF showed antifungal and antibacterial activity. The highest antibacterial activity was found against Vibrio damsela where a time-kill assay revealed a decline in the amount of viable V. damsela. For fungi, the highest activity was observed against Aspergillus terreus. Using the SRB test on HepG2, the anti-proliferative efficacy of the ERF was evaluated. Cell cycle analysis was utilized to determine autophagic cell death. The ERF prevented the proliferation of the HepG2 cell line with an IC50 of 67.182 µg/µL. The extract primarily promoted apoptosis in HepG2 cells by accumulating hypodiploid cells in the sub-G0/G1 phase, increased caspase 3/7 activity, and caused considerable autophagic cell death in apoptosis-deficient cells. Finally, the observed elevation of cancer cell death indicated that ERF had substantial anticancer potential against HepG2 cells

Antihyperlipidemic effect of bread fortified with potato peel powder against Triton X-100-induced hyperlipidemia in male albino rats

The present investigation aimed to improve the nutritional and healthy values and evaluate the influence of bread fortified with dried potato peels (BPP) on Triton X-100-induced hyperlipidemia in male albino rats. The findings demonstrated that BPP lowered hepatic triglycerides and total cholesterol while increasing high-density lipoprotein (HDL-C). BPP exhibited potential lipid-lowering and hepatoprotective actions that were generated by the reduction of oxidative damage and preservation of the non-enzymatic and enzymatic antioxidant systems compromised by hyperlipidemic condition. Furthermore, BPP considerably enhanced the mRNA expression of AMPKα (AMP-activated protein kinase-alpha), suppressed the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase alpha (ACCα), and decreased the mRNA expression of the adipogenic transcription factor SREBP-1c (sterol regulatory element-binding protein-1c), which are essential regulators of hepatocyte lipid metabolism. A histopathological assessment of the liver confirmed the results. In conclusion, this investigation revealed a positive impact of bread fortified with BPP therapy in preventing hyperlipidemia

Assessment of Bioactive Phytochemicals and Utilization of <i>Rosa canina</i> Fruit Extract as a Novel Natural Antioxidant for Mayonnaise

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g−1), total flavonoids content (26.31 ± 1.03 mg QE g−1), and free radical scavenging activity. The GC–MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and <i>in silico</i> insights

From Crossref journal articles via Jisc Publications RouterHistory: received 2023-05-24, revised 2023-06-23, accepted 2023-06-25, epub 2023-07-20, issued 2023-07-20, published 2023-07-20, ppub 2023-12-31Article version: VoRPublication status: PublishedFunder: King Saud University, Riyadh, Saudi Arabia; Grant(s): RSPD2023R74

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and <i>in silico</i> insights

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.</p