Chemical constituents from Parrotia persica- Structural derivatization and their potential prolyl endopeptidase inhibition activity.

The current study was aimed to evaluate the prolyl endopeptidase (PEP) inhibitory activity of glutinol (1), azadiradione (2), quercetin 3-O-ß-d-glactopyranoside (3), catechin (4), quercetin (5), naringenin (6) isolated from Parrotia persica C. A. Mey. Naringenin (6) was further derivatized into 7-O-propargylnaringenin (7), 4',6',4″-O-propargylchalcone (8), and 4',4″-O-propargylchalcone (9). All compounds 1-9 were evaluated for their PEP inhibition activity. PEP is associated with several diseases, including dementia, and Alzheimer's disease (AD). Azadiradione (2) was less active with IC50 = 356.80 ± 2.9 µM, whereas quercetin (5) showed a potent activity with IC50 = 37.12 ± 2.2 µM, as compared to IC50 = 125.00 ± 1.5 µM of standard drug bacitracin. Naringenin (6) was found to be inactive, whereas its new analogues 7-9 were identified as potent inhibitors of PEP with IC50 = 35.20, 41.20, and 29.60 µM, respectively. Kinetic studies of active compounds indicated their modes of inhibition. Compounds 7-9 were found to be mixed-type inhibitors, while compound 5 was found to be non-competitive inhibitor.

Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles.

This study examines the manufacturing, characterization, and biological evaluation of platinum nanoparticles, which were synthesized by Enterobacter cloacae and coated with Bovine Serum Albumin (BSA) and Resveratrol (RSV). The formation of PtNPs was confirmed with the change of color from dark yellow to black, which was due to the bioreduction of platinum chloride by E. cloacae. BSA and RSV functionalization enhanced these nanoparticles' biocompatibility and therapeutic potential. TGA, SEM, XRD, and FTIR were employed for characterization, where PtNPs and drug conjugation-related functional groups were studied by FTIR. XRD confirmed the crystalline nature of PtNPs and Pt-BSA-RSV NPs, while TGA and SEM showed thermal stability and post-drug coating morphological changes. Designed composite was also found to be biocompatible in nature in hemolytic testing, indicating their potential in Biomedical applications. After confirmation of PtNPs based nanocaompsite synthesis, they were examined for anti-bacterial, anti-oxidant, anti-inflammatory, and anti-cancer properties. Pt-BSA-RSV NPs showed higher concentration-dependent DPPH scavenging activity, which measured antioxidant capability. Enzyme inhibition tests demonstrated considerable anti-inflammatory activity against COX-2 and 15-LOX enzymes. In in vitro anticancer studies, Pt-BSA-RSV NPs effectively killed human ovarian cancer cells. This phenomenon was demonstrated to be facilitated by the acidic environment of cancer, as the drug release assay confirmed the release of RSV from the NP formulation in the acidic environment. Finally, Molecular docking also demonstrated that RSV has strong potential as an anti-oxidant, antibacterial, anti-inflammatory, and anticancer agent. Overall, in silico and in vitro investigations in the current study showed good medicinal applications for designed nanocomposites, however, further in-vivo experiments must be conducted to validate our findings.

Vitamin C Alleviates the Negative Effects of Heat Stress on Reproductive Processes by Regulating Amino Acid Metabolism in Granulosa Cells.

Heat stress-induced biochemical alterations in ovarian follicles compromise the function of granulosa cells (GCs) and the developmental competence of oocytes. Summer heat stress can have a far-reaching negative impact on overall fertility and reproductive success. Together with the heat stress, the rise of assisted reproductive technologies (ART), potential confounding hazards of in vitro handling and the absence of systemic body support in ART makes it imperative to study the heat stress ameliorative effects of vitamin C under in vitro conditions. Using in vitro heat stress treatment of 43 °C for two hours in bovine GCs, we studied the effects of vitamin C on cell growth, oxidative stress, apoptosis and cell cycle progression together with a comprehensive metabolomics profiling. This study investigates the molecular milieu underlying the vitamin C (VC)-led alleviation of heat-related disruptions to metabolic processes in bovine GCs. The supplementation of VC ameliorated the detrimental effects of heat stress by reducing oxidative stress and apoptosis while restoring cell proliferation. Normal cell function restoration in treated GCs was demonstrated through the finding of significantly high levels of progesterone. We observed a shift in the metabolome from biosynthesis to catabolism, mostly dominated by the metabolism of amino acids (decreased tryptophan, methionine and tyrosine) and the active TCA cycle through increased Succinic acid. The Glutathione and tryptophan metabolism were important in ameliorating the inflammation and metabolism nexus under heat stress. Two significant enzymes were identified, namely tryptophan 2,3-dioxygenase (TDO2) and mitochondrial phenylalanyl-tRNA synthetase (FARS2). Furthermore, our findings provide insight into the significance of B-complex vitamins in the context of heat stress during VC supplementation. This study underscores the importance of VC supplementation in heat stress and designates multiple metabolic intervention faucets in the context of ameliorating heat stress and enhancing reproductive efficiency.