The aim of this study was to investigate the modulation of gut microbiota by fermented raspberry juice (FRJ) both in vitro and in vivo. Results showed that total phenolic content and antioxidant activities of FRJ reached the highest after fermentation for 42 h. Seventeen phenolic compounds were contained in FRJ, mainly including ellagic acid (496.64 ± 2.91 μg/g) and anthocyanins (total concentration: 387.93 μg/g). FRJ modulated the gut microbiota into a healthy in vitro status, with increase of valeric and isovaleric acids production. In healthy mice, all FRJ treatments improved the production of acetic, butyric and isovaleric acids as well as the gene expression of ZO-1, Claudin-1, Claudin-4, Ocdudin, E-cadherin and Muc-2. Moreover, variable gut microbial compositions were found among the groups fed diet-supplemented the different doses of FRJ, within low and median doses of FRJ may regulate the microbiota to a healthier state compared to the high dose supplementation. This study indicated that fermentation is a potential way to produce plant-based juices, which could reshape the gut microbiota and improve the host health.

This study investigated the protective effects of aged Pericarpium Citri Reticulatae ‘Chachi’ (PCR-C) on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells. According to HPLC analysis, PCR-C aged 10 years (PCR-C10) had the highest flavonoids content, especially polymethoxyflavones (PMFs), compared with the fresh peel of Citrus reticulata cv. ‘Chachiensis’ and PCR-C aged 1, 3, and 5 years. Then, flavonoids-rich PCR-C samples and non-flavonoids-rich PCR-C samples (NF) were prepared by extracting and purifying PCR-C of different aging periods, for further cell experiments. Pretreatment with flavonoids-rich PCR-C samples (particularly PCR-C10) considerably reversed t-BHP-induced oxidative damage in HepG2 cells by improving cell viability, increasing SOD activity and GSH levels and reducing the overproduction of ROS and MDA. Correlation analysis further indicated that the accumulation of PMFs, mainly 5,6,7,4′-tetramethoxyflavone and nobiletin, was the main reason that PCR-C10 maintained the redox balance in HepG2 cells. These findings provided direct evidence for the cellular antioxidant activity of aged PCR-C and a guide for PCR-C’s classification, authentication and rational use.

Caffeoylquinic acids, as plant-derived polyphenols, exhibit multiple biological activities such as antioxidant, anti-inflammatory, and neuroprotective activities. However, only limited information about their effect on longevity is available. In the current study, molecular docking was employed to explore the interactions between six representative caffeoylquinic acids and the insulin-like growth factor-1 receptor (IGFR), which is an important target protein for longevity. The results indicated that all six compounds were embedded well in the active pocket of IGFR, and that 3,5-diCQA exhibited the strongest affinity to IGFR. Moreover, ASP1153, GLU1080, ASP1086, and ARG1003 were the key amino acid residues during the interaction of these 6 compounds with IGFR. Furthermore, the lifespan extension effect of caffeoylquinic acids was evaluated in a Caenorhabditis elegans (C. elegans) model. The results revealed that all the caffeoylquinic acids significantly extended the lifespan of wild-type worms, of which 3,5-diCQA was the most potent compound. Meanwhile, 3,5-diCQA enhanced the healthspan by increasing the body bending and pharyngeal pumping rates and reducing the intestinal lipofuscin level. Further studies demonstrated that 3,5-diCQA induced longevity effects by downregulating the insulin/insulin-like growth factor signaling (IIS) pathway. This study suggested that the combination of molecular docking and genetic analysis of specific worm mutants could be a promising strategy to reveal the anti-aging mechanisms of small molecule natural compounds.

Intestinal secretory immunoglobulin A (sIgA)-improving function of Lactobacillus casei-fermented blueberry pomace (FBP) was investigated in this study. Male C57BL/6 mice were fed with control diet (CD) or high-fat diet (HFD) with or without FBP supplementation. Expressions of sIgA-associated genes/proteins were evaluated by quantitative polymerase chain reaction (qPCR), western blot and enzyme-linked immunosorbent assay (ELISA). Commensal microbiota in Peyer's patches (PPs) and caecal contents were analyzed by 16S rRNA Illumina sequencing and qPCR, respectively. FBP improved sIgA production in HFD mice at mRNA and protein levels. Akkermansia and Lactobacillus in PPs of HFD mice were statistically increased by FBP. Beneficial microbiota and short-chain fatty acids (SCFAs) in caecal contents were positively correlated with caecal immunoglobulins in HFD mice. FBP showed an ability to modulate intestinal microbiota, which improved sIgA production in HFD mice, warranting the potential use of berry by-products as functional ingredients in improving the intestinal immune barrier of HFD individuals.