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Extracellular clustering of amyloid-β (Aβ) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aβ1–42, Iowa mutation Aβ, Dutch mutation Aβ fibrils and oligomers exhibiting enhanced emission with high affinity. Importantly, F-SLCOOH can readily pass through the blood–brain barrier and shows highly selective binding toward the extracellular Aβ aggregates in real-time in live animal imaging of a 5XFAD mice model. In addition, a high concentration of F-SLCOOH in both brain and plasma of wildtype mice after intraperitoneal administration was found. The ex vivo confocal imaging of hippocampal brain slices indicated excellent colocalization of F-SLCOOH with Aβ positive NU1, 4G8, 6E10 A11 antibodies and THS staining dye, affirming its excellent Aβ specificity and targetability. The molecular docking studies have provided insight into the unique and specific binding of F-SLCOOH with various Aβ species. Importantly, F-SLCOOH exhibits remarkable anti-fibrillation properties against toxic Aβ aggregate formation of Aβ1–42, Iowa mutation Aβ, and Dutch mutation Aβ. F-SLCOOH treatment also exerts high neuroprotective functions and promotes autophagy lysosomal biogenesis in neuronal AD cell models. In summary, the present results suggest that F-SLCOOH is a highly promising theranostic agent for diagnosis and therapeutics of AD. [ABSTRACT FROM AUTHOR]

This article discusses a study on the anti-angiogenic properties of diosgenin saponin from fenugreek using zebrafish embryos as a model organism. The study found that diosgenin inhibits angiogenesis in zebrafish embryos by suppressing VEGF-A expression and may also be linked to the inhibition of the NF-¿B pathway. The results suggest that natural substances like diosgenin have potential therapeutic effects against diseases characterized by pathological angiogenesis, such as cancer. However, the study has limitations, including a limited dose range, a brief treatment period, and reliance on a single model organism. Further research is needed to understand the underlying mechanisms and their clinical relevance. [Extracted from the article]

The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress. [ABSTRACT FROM AUTHOR]

Background: The study focused to long-term effect of aspartame on membrane bound enzymes, oxidative stress markers and histopathology in brain regions of Wistar albino rats. Hence it is essential to observe whether the chronic aspartame administration (75 mg/kg b. wt) could release methanol and induce oxidative stress in the rat brain. Many reports are available on the use of aspartame as it releases methanol during metabolism. Methods: To mimic the human methanol metabolism the methotrexate treated rats were included to study the aspartame effects and the gamma glutamyl transpeptidase, NO, H2O2 and the membrane bound enzymes were observed in brain discrete regions. Results: There was a significant increase in all the parameters except with a significant decrease in membrane bound ATPases and creatine kinase. Luxol fast blue (LFB) staining were performed on brain cerebellum region which showed histopathological changes in aspartame treated MTX animals which showed a marked decrease in the density of white matter, intensity of staining and no. of stained neuron cells when compared to control and MTX control animals. Conclusion: Moreover, the increases in some of these enzymes were due to methanol per se and its metabolite may be responsible for the generation of oxidative stress and histopathology in brain regions. [ABSTRACT FROM AUTHOR]