RA-PR058, a novel ramalin derivative, reduces BACE1 expression and phosphorylation of tau in Alzheimer’s disease mouse models

Animal Cells and Systems, Journal Year: 2025, Volume and Issue: 29(1), P. 122 - 134

Published: Feb. 7, 2025

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by cognitive decline, anxiety-like behavior, β-amyloid (Aβ) accumulation, and tau hyperphosphorylation. BACE1, the enzyme critical for Aβ production, has been major therapeutic target; however, direct BACE1 inhibition associated with adverse side effects. This study investigates potential of RA-PR058, novel ramalin derivative, as multi-targeted modulator AD-related pathologies. The effects RA-PR058 were evaluated in vitro vivo. In studies used SH-SY5Y cells under oxidative stress conditions to assess expression, while vivo studied 3xTg-AD mice following one month oral treatment. Behavioral assessments, biochemical analyses, transcriptomic profiling, pharmacokinetic evaluations performed determine efficacy RA-PR058. significantly reduced stress-induced expression decreased cortical mice. treatment alleviated behavior phosphorylation at disease-relevant sites (Ser202/Thr205, Thr231, Ser396). Transcriptomic analysis revealed RA-PR058-mediated gene changes related central nervous system development, response hypoxia, neuroactive ligand-receptor interactions, suggesting broader regulatory on pathways. Pharmacokinetic demonstrated that exhibits high metabolic stability, minimal cytochrome P450 moderate blood-brain barrier penetration. demonstrates multi-target AD reducing hyperphosphorylation, coupled favorable pharmacokinetics. Additional are needed clarify molecular mechanisms, but may represent promising advancement addressing AD's complex pathology.

Language: Английский

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Evaluation of antiobesogenic properties of fermented foods: In silico insights

Journal of Food Science, Journal Year: 2025, Volume and Issue: 90(3)

Published: March 1, 2025

Obesity prevalence has steadily increased over the past decades. Standard approaches, such as energy expenditure, lifestyle changes, a balanced diet, and use of specific drugs, are conventional strategies for preventing or treating disease its associated complications. Fermented foods their subsequent bioactive constituents now believed to be novel strategy that can complement already existing approaches managing this disease. Recent developments in systems biology bioinformatics have made it possible model simulate compounds interactions. The adoption silico models contributed discovery fermented product targets helped testing hypotheses regarding mechanistic impact underlying functions food components. From studies explored, key findings suggest affect adipogenesis, lipid metabolism, appetite regulation, gut microbiota composition, insulin resistance, inflammation related obesity, which could lead new ways treat these conditions. These outcomes were linked probiotics, prebiotics, metabolites, complex substances produced during fermentation. Overall, show promise innovative tools obesity management by influencing metabolic pathways overall health.

Language: Английский

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Medium-Chain Fatty Acids Extracted from Black Soldier Fly (Hermetia illucens) Larvae Prevents High-Fat Diet-Induced Obesity In Vivo in C57BL/6J Mice

Animals, Journal Year: 2025, Volume and Issue: 15(10), P. 1384 - 1384

Published: May 10, 2025

Obesity is a chronic disease associated with an increased dietary fat intake and reduced physical activity, posing significant health risks, including metabolic disorders, cardiovascular diseases, diminished quality of life. This study investigated the anti-obesity potential medium-chain fatty acids (MCFAs) derived from black soldier fly larvae (BSFL-MCFAs) in male C57BL/6J mice fed high-fat diet (HFD). Lauric acid (>50% total BSFL lipids) was predominant acid. Mice supplemented BSFL-MCFAs exhibited significantly lower weight gain food efficiency ratios (FERs) than HFD-fed mice, despite similar intake. Medium-chain supplementation also attenuated HFD-induced increases triglycerides, cholesterol, low-density lipoprotein cholesterol levels while improving cardiac risk indices. Furthermore, serum glucose leptin levels, mitigated hypothalamic endoplasmic reticulum stress marker expression, decreased alanine transaminase indicating protective effects against obesity-related dysregulation. These findings suggest that enhance energy expenditure thermogenesis, thereby contributing to effective management obesity prevention. As sustainable functional lipid source, hold promise as feed additive for animals ingredient preventing pet obesity, offering innovative approach combat its risks.

Language: Английский

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Mealworm hydrolysate ameliorates dexamethasone-induced muscle atrophy via sirtuin 1-mediated signaling and Akt pathway

npj Science of Food, Journal Year: 2025, Volume and Issue: 9(1)

Published: May 13, 2025

Language: Английский

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Untargeted metabolomics and PacBio analysis on bioactive components and microbial community in co-fermentation of black soldier fly larva

Food Research International, Journal Year: 2024, Volume and Issue: 197, P. 115304 - 115304

Published: Nov. 6, 2024

Language: Английский

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