Blackcurrant extract (BCE), rich in anthocyanins, has demonstrated significant potential in lipid level reduction. In this study, network pharmacology was applied to predict the lipid-lowering metabolic mechanism of BCE. Upon treatment with BCE (100 μg/mL), lipid accumulation was significantly reduced in both the HepG2 cells in vitro and the high-glucose-fed Caenorhabditis elegans (C. elegans) in vivo by 46.06% and 56.68%. Additionally, the lifespan of C. elegans was significantly prolonged by BCE treatment, its stress tolerance and antioxidant capacity were enhanced, and aging-related markers (e.g., lipofuscin accumulation) were altered. Subsequent qPCR analysis revealed that genes associated with the SBP-1/SREBP pathway (sbp-1, fat-6, and fat-7) were down-regulated by BCE, while genes in the NHR-49/PPARα pathway (nhr-49, acs-2, ech-1.1, and cpt-2) were up-regulated. Furthermore, Oil Red O staining and triglyceride (TG) content assays demonstrated that the hypolipidemic effect of BCE was absent in nhr-49, fat-6, and fat-7 mutant strains of C. elegans. The current findings were validated by molecular docking, indicating that abnormal fat accumulation in C. elegans was alleviated by BCE treatment via the SBP-1 and NHR-49 pathways. In summary, these findings indicated that BCE exerted a lipid-lowering effect and provided novel insights and research materials for the development of natural lipid-lowering medications and health products.
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Wolfberry (Lycium barbarum L.) is a medicinal herb with anti-aging and neuroprotective effects. The purpose of this study was to explore the enhanced neuroprotective effects of red wolfberry water extract (RW), and brown wolfberry water extract (BBW). The reduced percentage of reducing sugar in BBW was shown to be 62.8%, 64.3%, 39.8%, and 11.6% for glucose, fructose, maltose, and lactose compared to those of RW, as well as free amino acids. And the contents of total phenols and total flavonoids were increased by 62.0% and 51.0%. Melanoidins (1.00%) were first isolated from BBW. RW and BBW increased anti-stress abilities (oxidative stress: 24.2% vs. 35.7%, and heat stress: 17.78% vs. 57.57%) while decreasing the reactive oxygen species (ROS) levels in vivo. RW and BBW reduced the rate of paralysis and odor cognitive deficits. At the same time, RW and BBW reduced the number of fluorescent spots of Aβ::GFP. The RW and BBW activated autophagy by upregulating the gene levels (bec-1, lgg-1, lgg-2, unc-51, vps-34, atg-5, atg-18, and sqst-1). Additionally, BBW promoted the nuclear-cytoplasmic ratio of DAF-16::GFP and fluorescence intensity of SOD-3::GFP by 39.4 and 1.16 fold. This study laid a new insight for exploring the Maillard reaction in improving the anti-Alzheimer's disease (AD) activity of wolfberry.
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This study aimed to investigate the anti-aging effects of black rice-anthocyanin (BRA) in Drosophila melanogaster and HUVEC cells. In this study, the strong antioxidant activity of BRA in HUVEC cells, D. melanogaster of lifespan extension, and molecular mechanism were elucidated. Firstly, the BRA increased enzyme activities of superoxide dismutase (SOD) and catalase (CAT), as well as the expression of phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) protein while decreasing the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) in both H2O2-induced HUVEC cells and D. melanogaster. Secondly, the BRA extended the lifespan of D. melanogaster by improving crawling ability and intestine abilities in the microbial environment, barrier function, and number of autophagic lysosomes, as well as inhibiting the abnormal multiplication of stem cells in the intestine. Thirdly, the BRA downregulated expression levels of Akt-1 and mTOR in D. melanogaster while upregulated downstream autophagy gene expression levels of Atg1, Atg5, Atg8a, and Atg8b, as well as the expression levels of SOD, CAT, and 4E-binding protein. Lastly, the anti-aging mechanism was also verified by both the computerized molecular simulation and network pharmacology. Thus, the prolonged lifespan of D. melanogaster by blocking the mTOR pathway and activating autophagy, which could be further used for improving health and prolonging life.
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Research has shown that dysregulation of intestinal homeostasis and autophagy pathways significantly contributes to aging. Anthocyanins (AC) exhibit potent antioxidant properties and improve the intestinal environment improvement. Therefore, this study used cells and Drosophila as models to explore the life-prolonging effects and mechanisms of blackcurrant extract (BCE). BCE was effective against H2O2-induced oxidative damage and enhanced the antioxidant capacity of L929 and SH-SY5Y cells. In vivo, BCE prolonged the lifespan of Drosophila and improved their resistance to combat multi-factorial stress. Meanwhile, BCE improved the intestinal barrier function of Drosophila, restored the gut microenvironment, increased autophagy levels, and inhibited the abnormal proliferation of intestinal precursor cells (Esg). BCE upregulated the mRNA expression levels of antioxidant genes (Cat, Sod1, Sod2) and autophagy genes (Atg1, Atg5, Atg8a, Atg8b) in Drosophila. RNAi experiments verified the critical role of autophagy genes Atg5 and Atg8b in anti-aging. In addition, BCE rescued motor deficits and brain vacuolization in Drosophila models with Alzheimer’s disease (AD). In summary, BCE extract alleviated intestinal homeostasis imbalance and activated the autophagy pathway to extend lifespan and salvage neurodegeneration in aging Drosophila. This provides a theoretical foundation for developing anti-aging functional foods from blackcurrants.
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