BackgroundThai Mucuna pruriens (T-MP) has been used as a traditional medicine for treating many neurological conditions due to its antioxidant and neurorestorative properties. Aim of the studyThis study was to explore the effects of T-MP seed extract on ethanol withdrawal syndrome (EWS) in mice. MethodsMice were administered either normal saline solution (NSS) or 2 g/kg of 20% ethanol intraperitoneally once daily for 10 days. Behavioral symptoms of EWS were evaluated at 12-, 24-, and 36-hours after the last dose of ethanol using the elevated plus maze (EPM), light-dark box (LDB), and tail suspension test (TST). After determining the best time interval to detect EWS, a new set of mice were induced to have EWS, at 23 h after the last ethanol dose, mice were treated with either NSS (PO), diazepam (4 mg/kg, IP), or T-MP seed extract (600 mg/kg, PO). Behavioral tests were conducted one hour after treatment. ResultsIn the ethanol withdrawal mice, anxiety- and depressive-like behavior representing EWS were seen in LDB, EPM and TST, especially at the 24-hour after the final ethanol dose. At 36-hour after the final ethanol dose, although the anxiety-like behavior could be seen in LDB and EPM, whereas no significant depressive-like in TST was observed. Treatment with DZP or T-MP could significantly reduce the anxiety- and depressive-like symptoms of EWS at 24-hour after last dose of ethanol. In addition, treatment with T-MP, but not DZP, significantly reduced the total immobility time when compared to the control ethanol withdrawal group. ConclusionAccording to this study, it was discovered that T-MP seed extract could potentially offer a beneficial effect in managing anxiety- and depression-like behaviors in EWS in mice.

BackgroundColorectal cancer (CRC) is one of the most common and deadly malignant neoplasms worldwide. It is associated with multiple lifestyle risk factors such as poor diet, physical inactivity, alcohol and red meat consumption, smoking, and obesity. Consequently, studies have been conducted on the protective activity of bioactive compounds present in some foods against CRC, making it necessary to understand how diet can affect human health. In this sense, coffee, the second most consumed beverage in the world, is a major source of phytochemicals associated with a possible antitumor effect on CRC cells. PurposeThis study aimed to analyze the chemopreventive potential of green and roasted coffee extracts on HT-29 CRC cells cultured in 2D and 3D models. MethodsFlow cytometry was employed to quantify propidium iodide and DiOC6 uptake, ROS production, phosphatidylserine exposure, and cell cycle progression. In addition, cells and spheroids were analyzed by light microscopy to identify morphological changes. ResultsThe results showed that, under the employed conditions, treatment with both extracts had a concentration-dependent cytotoxic effect. Decreased cell viability was associated with mitochondrial membrane hyperpolarization, prooxidant effect, increased phosphatidylserine exposure, and changes in the G1 phase of the cell cycle. ConclusionFor the evaluated cell markers, 3D cultures required higher doses to achieve significant cytotoxic effects when compared to monolayer cultures. Since 3D cultures favor the formation of complex cell–cell interactions, this model offers a closer look at in vivo conditions for evaluating the toxicity and preclinical efficacy of potential chemopreventive agents for CRC. The experimental evidence from this study supports the 3R principles of replacement, reduction, and refinement for toxicological research in the pharmaceutical industry.

ObjectiveThis study was designed to investigate the nephroprotective effect and mechanism of action of a methanolic extract of Petiveria alliacea leaves (MEPAL) in streptozotocin-induced diabetic nephropathy (DN) in rats. MethodsTwenty-five Wistar rats were randomly distributed into five groups. Type-2 diabetes was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight low dose) in citrate buffer (pH 4.5) after administering fructose for two weeks. Diabetic rats with fasting blood glucose above 250 mg/dl were considered diabetic and were divided into: control (distilled water-treated), diabetes-control, diabetes + metformin (100 mg/kg), diabetes + MEPAL (150 mg/kg), and diabetes + MEPAL (300 mg/kg) via oral gavage once daily for 14 days. At the end of the experimental period, the rats were euthanized, and renal tissues were collected for biochemical and histological analyses. Renal apoptosis and marker gene expression were measured by real-time quantitative PCR. ResultsMEPAL significantly attenuated diabetic-induced increases in blood glucose levels, kidney body weight, and renal functional indices (ALP, urea, uric acid, and creatinine). MEPAL treatment resulted in a significant reduction in MDA levels and increased activities of SOD, CAT, and GSH levels. In addition, MEPAL protects against DN by significantly downregulating the mRNA expression of cAMP, PKA, CREB, and cFOS and upregulating the Bcl-2 gene, indicating that the nephroprotective effect of MEPAL is due to the modulation of the cAMP/PKA/CREB/cFOS signaling pathways. Furthermore, in the STZ-induced diabetic rats, the kidney tissue showed a thickened basement membrane and degenerated glomerulus while MEPAL and metformin treatment preserved the basement membrane and degenerated glomerulus in treated rats. Conclusionthe findings of this study suggest that MEPAL protects against renal damage in streptozotocin-induced diabetic nephropathic rats.