| 1. |
- Turkez, H., et al.
(författare)
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In vitro transcriptome response to propolis in differentiated SH-SY5Y neurons
- 2021
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Ingår i: Journal of food biochemistry. - : Wiley. - 0145-8884 .- 1745-4514. ; 45:12
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Tidskriftsartikel (refereegranskat)abstract
- Propolis is the extract of a resinous compound that protects plants from both cold and microorganism attack and has gained a strong and sticky property because it is transformed after being collected by honey bees. Up to date, many studies have shown that propolis exhibited various beneficial biological activities, such as antifungal, antibacterial, antiviral, antioxidant, antimutagenic, and antitumor effects. Recent reports propounded the in vitro and in vivo neuroprotective effect of propolis; however, the exact molecular genetic mechanisms are still unclear. Therefore, we aimed to investigate the toxicogenomic and beneficial properties, including cytotoxic, antioxidant, apoptotic/necrotic as well as genotoxic effects of propolis (1.56–200 µg/ml) on differentiated SH-SY5Y neuronal cells. Additionally, microarray analysis was conducted on cell cultures following propolis application to explore gene differentiation. Differentially expressed genes were further analyzed using string software to characterize protein–protein interactions between gene pathways. Our results revealed that propolis applications could not have a prominent effect on cell viability even at concentrations up to 200 µg/ml. The highest propolis concentration induced apoptotic rather than necrotic cell death. The alterations in gene expression profiles, including CYP26A1, DHRS2, DHRS3, DYNC1I1, IGF2, ITGA4, SVIL, TGFβ1, and TGM2 could participate in the neuroprotective effects of propolis. In conclusion, propolis supplementation exerted remarkable advantageous; thus, it may offer great potential as a natural component in the prevention and treatment of neurodegenerative disorders. Whole-genome gene expression pattern following propolis application was investigated for the first time in neuronal cell culture to fill a gap in the literature about propolis toxicogenomics. Practical applications: Propolis is a very rich product in terms of benefits. In addition to its antibacterial, antiviral, antifungal, and anti-inflammatory content, it is known to have preventive and therapeutic properties for many different ailments. On the other hand, molecular mechanisms of propolis on gene expression differentiations haven't been investigated until now. Moreover, gene expression pattern is vital for all living organisms to maintain homeostasis. Thus, we conduct an experiment series for analyzing gene expression differentiation effects on neuronal cells to understand beneficial properties of propolis. Hence, it could be possible to comment on the use of propolis as a nutritional factor and beneficial diet.
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| 2. |
- Yulug, B., et al.
(författare)
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Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
- 2023
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Ingår i: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
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| 3. |
- Battisti, Umberto Maria, et al.
(författare)
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Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
- 2023
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.
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