Procyanidin B2 (PB2), a dimer of oligomeric procyanidins, has been reported to ameliorate abnormal glucose metabolism; however, its efficacy in regulating redox-related insulin resistance (IR) and underlying mechanism has not yet been studied. Currently, antioxidant activity and digestive enzyme inhibitory tests were applied to screen the preliminary chemopreventive effect of PB2 on glucose metabolism dysfunction, further computational biology and molecular verification to elucidate its mechanism on improving IR. The results indicated that PB2 had limited antioxidant property against ROS and inhibitory property on digestive enzyme. Network pharmacology analysis implied that PI3K/AKT and FoxO pathways were the main targeted by PB2 to combating IR. Further molecular data demonstrated that PB2 promoted glycogen synthesis by activation of PI3K/AKT-Nrf2 signaling pathway via promoting posttranscriptional protein stability, nuclear translocation of Nrf2 and ARE binding ability, and inhibited gluconeogenesis by stimulating FoxO1 phosphorylation to reduce the expression of downstream G6Pase. Innovatively, molecular docking coupled with different Pull-Down assays revealed that PB2 could directly bind with AKT, Nrf2 and GSK3β, suggesting PB2 may improve IR via regulation of PI3K/AKT-Nrf2-GSK3β signaling, more than FoxO1 signaling pathway; subsequently, Nrf2 could directly bind with GSK3β, reinforcing evidence for PB2-Nrf2-GSK3β complex formation. Besides, co-treatment with PI3K/AKT and Nrf2 inhibitors or siRNAs highlighted the essential role of Nrf2 activation in PB2-contributed IR improvement. Moreover, PB2 has also been validated to exert its effect via regulation of PI3K/AKT-Nrf2-GSK3β signaling pathway in vivo. Therefore, these findings suggest that PB2 is a potent and promising compound to ameliorate glucose metabolism by targeting IR.

Low-molecular-weight polysaccharides (RLPs) extracted from Rosa laevigata fruits showed multiple biofunctions in Asia. This study aimed to investigate its anti-inflammatory obesity effect in high-fat diet-fed rats and further elucidated the underlying molecular mechanism by multi-omics methods. The results showed that RLPs administration had significantly restored immune organ indexes and reduced body weight gain. RNA-seq revealed that the effect of RLPs was partially attributed to its regulation on PPARs signaling by increasing the expressions of Scd, Acox3 and Hmgcs2, and on other redox-related pathways by decreasing the expressions of Cyp2e1, Il1-r1 and Lbp. Moreover, 16S rRNA sequencing coupled with metagenome sequencing showed that RLPs had significantly reduced the ratio of Firmicutes/Bacteroidetes from 8.01 to 2.37, and significantly increased the relative abundances of Alistipes, Prevotella, and Akkermansia from 0.36%, 1.10% and 2.61% to 0.65%, 2.37% and 4.42%, respectively. Spearman correlation analysis result indicated that the abundances of Lachnospiraceae, Prevotella and Bacteroidales were significantly negatively correlated with obesity phenotype, liver function and inflammatory factors. These results revealed that RLPs exerted significant anti-inflammatory obesity property partially via regulation on gut microbiota interface and the redox balance. Therefore, RLPs could be a promising functional food resource with the potential for redox imbalance-related diseases chemoprevention.

The present study is focused on investigation of the health protective effect of yellow rice wine (YRW) in mice and the potential underlying mechanism. Symptoms of aging were induced in mice by using D-galactose (D-gal), and different doses of YRW (4, 8, and 12 mL/kg BW) were orally administrated to D-gal-treated mice for a period of six weeks. The in vivo data obtained in the present study preliminary indicated that YRW markedly increased the activity of antioxidant enzymes and reduced the concentration of MDA both in the brain and liver. Furthermore, a forced swim test showed that moderate intake of YRW (8 mL/kg BW) significantly decreased the duration of immobility, reduced the blood content of urea nitrogen and lactic acid, and increased hepatic glycogen storage. Besides, results from the Morris water maze test suggested that YRW significantly reversed cognitive impairment and also alleviated neuroapoptosis in the experimental mice by regulating the gene expressions of Bax/Bcl-2 and caspase-3. The above results indicated YRW has a potential anti-aging effect in mice and provided us certain molecular evidence for this action.