Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)₂)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)₂ (20 ppm), APE (200 ppm) or Pb(Ac)₂ (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)₂-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)₂ exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)₂-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.

Palmitic acid (PA) can lead to intestinal epithelial barrier dysfunction. In this study, the protective effects and working mechanisms of 6-shogaol against PA-induced intestinal barrier dysfunction were investigated in human intestinal epithelial Caco-2 cells. Transepithelial electrical resistance (TEER), paracellular flux, qRT-PCR, immunofluorescence, and Western blot experiments showed that the 24-h treatment with 400 μM PA damaged intestinal barrier integrity, as evidenced by a reduction of 48% in the TEER value, a 4.1-fold increase in the flux of fluorescein isothiocyanate-dextran 4000 (FD-4), and decreases in the mRNA and protein expression of tight junction (TJ)-associated proteins (claudin-1, occludin, and ZO-1), compared with the control. The PA treatment significantly (p < 0.05) increased the levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α)) in Caco-2 cells due to the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylated nuclear factor kappa-B (NF-κB) proteins, and downregulation of miR-216a-5p (which directly targeted TLR4). Co-treatment with PA and 6-shogaol (2.5 μM) significantly (p < 0.05) attenuated PA-induced changes through regulation of TJs via the miR-216a-5p/TLR4/NF-κB signaling pathway. This study provides insights into the functions and working mechanisms of 6-shogaol as a promising food-derived agent against PA-induced intestinal epithelial barrier dysfunction.

Quercetin is a flavonol found in edible plants and possesses a significant anticancer activity. This study explored the mechanism by which quercetin prevented liver cancer via inducing apoptosis in HepG2 cells. Quercetin induced cell proliferation and apoptosis through inhibiting YY1 and facilitating p53 expression and subsequently increasing the Bax/Bcl-2 ratio. The results revealed that YY1 knockdown promoted apoptosis, whilst YY1 overexpression suppressed apoptosis via direct physical interaction between YY1 and p53 to regulate the p53 signaling pathway. Molecular docking using native and mutant YY1 proteins showed that quercetin could interact directly with YY1, and the binding of quercetin to YY1 significantly decreased the docking energy of YY1 with p53 protein. The interactions between quercetin and YY1 protein included direct binding and non-bonded indirect interactions, as confirmed by cellular thermal shift assay, UV-Vis absorption spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. It was likely that quercetin directly bound to YY1 protein to compete with p53 for the binding sites of YY1 to disrupt the YY1-p53 interaction, thereby promoting p53 activation. This study provides insights into the mechanism underlying quercetin’s anticancer action and supports the development of quercetin as an anticancer therapeutic agent.

Catechin-loaded folate-conjugated chitosan nanoparticles (CFC-NPs) were synthesized through ionic gelation reactions between folate-modified chitosan and sodium tripolyphosphate. Their chemical structures, size distribution and morphology, drug loading capacity and entrapment efficiency, in vitro release behavior, and anti-proliferative effects were investigated. Results showed that CFC-NPs dispersed as a near-spherical shape with an average diameter of 255 nm. Drug loading capacity and entrapment efficiency reached 8.66–11.53% and 19.02–43.28%, respectively. Meanwhile, the loaded catechin exhibited a sustainable release from the nanoparticles, with the cumulative release ratio being 75.20% over 36 h. Blank folate-conjugated chitosan nanoparticles (FC-NPs) at 0.5 mg/mL had little or no cytotoxicity toward MCF-7 and HepG2 cells, while CFC-NPs had significant anti-proliferative activity in a dose-dependent manner. After incubation for 36 h, cell viability reached 35.22 ± 3.42% and 58.44 ± 3.85% in MCF-7 and HepG2 cells, respectively. These results suggest that CFC-NPs might be effective carrier of catechins with antitumor activity.