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.

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.

Although it is known that the accumulation of methylglyoxal (MGO) and advanced glycosylation end products (AGEs) results in oxidative injury, the comparison between caffeic acid (CA) and chlorogenic acid (CGA) against oxidative damage remains unclear. Therefore, this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans. The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology. First, CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential, reducing ROS production and apoptosis, and promoting the expression of NRF2 translocation and downstream genes, which were consistent with the results of molecular docking, molecular dynamics, and covariance matrix simulations. Second, treatment with ML385 (Nrf2 inhibitor) eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA. Third, CA exhibited stronger capacities in extending lifespan, inhibiting ROS production, and increasing SKN-1 proportion than CGA in C. elegans. Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA, which might be related to the alteration of the protein α-helix. Therefore, considering the higher antioxidant effects of CA, it can be used as a promising antioxidant natural drug resource.

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.

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.

Hyperoside and quercetin are similar in molecular structures. In this study, the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor (erythroid-2-derived)-related factor 2 (Nrf2) pathway predicted by network pharmacology. And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H₂O₂-induced HepG2 cells and Caenorhabditis elegans. The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage, which was proved by improved cell viability, decreased reactive oxygen species (ROS) production, decreased cellular apoptosis, and alleviated mitochondrial damage. In addition, quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated mRNAs, increasing the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and reducing the cellular malondialdehyde (MDA) content. Quercetin was superior to hyperoside in prolonging the lifespan of worms, decreasing the accumulation of lipofuscin, inhibiting ROS production, and increasing the proportion of skn-1 in the nucleus. With the Nrf2 inhibitor ML385, we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway. Furthermore, molecular docking and dynamics simulations demonstrated that the quercetin- Kelch-like ECH-associated protein 1 (Keap1) complex was more stable than the hyperoside-Keap1 complex. The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role. Overall, quercetin had a better antioxidant than hyperoside.

Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties. In this study, PC12, HepG2 cells, and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms. The results showed that naringin inhibited H₂O₂-induced decline in cell viability and decreased the content of reactive oxygen species in cells. Meanwhile, naringin prolonged the lifespan of f lies, enhanced the abilities of climbing and the resistance to stress, improved the activities of antioxidant enzymes, and decreased malondialdehyde content. Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells. Moreover, naringin down-regulated the mRNA expressions of inr, chico, pi3k, and akt-1, and up-regulated the mRNA expressions of dilp2, dilp3, dilp5, and foxo, thereby activating autophagy-related genes and increasing the number of lysosomes. Furthermore, the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling (IIS) pathway and activating the autophagy pathway, which was consistent with the result of network pharmacological predictions.

The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells. In this study, SD rats were divided into the normal chow diet group (NCD), high fat diet group (HFD), three treatment groups feeding high-fat diet with naringenin (100, 200, 400 mg/kg) for 12 weeks. Results indicated that naringenin treatment decreased total cholesterol (TC), triglyceride (TG) and the non-high-density lipoprotein cholesterol (non-HDL-C) levels in serum. Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats. In addition, naringenin (25−75 µg/mL) decrease TG and TC levels in 3T3 mature adipocytes. The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology. Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes. Meanwhile, naringenin increased the AMPK (AMP-activated protein kinase) activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes. And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C. Molecular docking results indicated that naringenin could bind to AMPK protein. These results indicated naringenin reduced lipid accumulation through AMPK pathway.