內(nèi)容: Pomegranate seed oil (PSO) mainly consisted of punicic acid (PunA), has gained attention due to rich conjugated linolenic acids and potential application in the improvement of various diseases. The aim of this study was to explore the ability of PunA to modulate lipid metabolism associated with non-alcoholic fatty liver disease (NAFLD) and explore the emerging role of the gut microbiota in modulating hepatic lipid metabolism. In this regard, PunA’s capacity was evaluated through C57BL/6J fed with a choline and L-amino acid defined high fat diet (CDAHFD). Mice were randomly divided into 4 groups and fed with control diet (low fat diet), CDAHFD + 2% PSO, CDAHFD + 0.2% curcumin (Cur) + 2% corn oil (positive control), or vehicle alone (CDAHFD + 2% corn oil). Collected results indicated that supplement of PunA improved hepatic lipid profile. PunA administration also ameliorated hepatic steatosis and lipid accumulation. mRNA analysis showed that PunA exerted ameliorative effect on hepatic lipid accumulation by downregulating the mRNA expression of Dgat1, Scd-1, Srebp-1c, but increasing expression level of Cpt-1α. Metagenomic analysis discovered that PunA increased species diversity and richness of intestinal microbiota, promoted proliferation of beneficial commensals and restraining the endotoxin-producing microorganisms in cecum of CDAHFD-administrated mice. Furthermore, PunA suppressed lipid accumulation and lipid droplet formation in a cell NAFLD model in vitro. Overall, PunA exhibited anti-lipogenic and lipid-lowering effects, improvement of intestinal flora. In summary, PunA could be a candidate for the exploitation of functional foods or nutraceuticals aiming NAFLD.

內(nèi)容: Infants exhibit diminished susceptibility to external infections, a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract. Nonetheless, a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages. In this study, the impact of early intervention with Bifidobacterium bifidum, Bifidobacterium breve, and Bifidobacterium longum on neonatal rats infected with Salmonella enterica serovar Typhimurium SL1344 were compared. The study encompasses various immunity levels, including gut immunity, central immunity (thymus), peripheral immunity (spleen), and brain immunity. Following Salmonella infection, significant alterations in neonatal rats were observed in growth and developmental levels, immune markers, cytokine levels, balance of T lymphocyte subpopulations, intestinal barrier function, and blood-brain barrier integrity. Compared with B. breve and B. longum, B. bifidum demonstrated more pronounced efficacy in regulating these physiological processes. By conducting multi-level analyses of gut microbiota, bifidobacterial community, colonic content metabolomics, and serum metabolomics, the significance of B. bifidum’s role is underscored, and the immune-enhancing function of messenger metabolites is unveiled. Among these metabolites, γ -L-glutamyl-L-glutamic acid and orotic acid were found to be shared by all 3 species, while hippuric acid and 1a,1b-dihomo prostaglandin F2α were unique to B. bifidum, and DL-arginine was specific to B. longum. Overall, this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections, emphasizing the significant role of B. bifidum.

內(nèi)容: This study investigated the therapeutic effects on metabolic syndrome (MetS) and the impact on the intestinal barrier and gut microbiota of Fu brick tea aqueous extracts (FTE) on MetS in rats fed with a high-fat diet (HFD). Here, the results showed that FTE supplement significantly reduced HFD-induced weight gain, adiposity, dyslipidemia, fasting blood glucose (FBG) increment, and non-alcoholic fatty liver disease (NAFLD). Moreover, FTE supplement resulted in a decline in lipopolysaccharide (LPS) level and attenuation of colonic inflammation and oxidative stress to protect the intestinal barrier function. FTE supplement also maintained the intestinal barrier integrity by improving histological appearance and promoting ZO-1, Occludin, and Claudin-1 protein expression levels. Meanwhile, FTE supplement alleviated the gut microbiota dysbiosis by enhancing the Firmicutes/Bacteroidetes (F/B) ratio and stimulating the colonization of probiotic bacteria such as Akkermansia, Lactobacillus, Adlercreutzia, and Bacteroides. These findings collectively suggest that Fu brick tea could alleviate MetS and MetS-associated traits with the mechanism relevant to the protection of intestinal barrier and gut microbiota regulation.

內(nèi)容: Lifestyle is related to many chronic diseases, such as knee osteoarthritis (KOA). Food intake is important because it can be controlled. However, the causal relationship of food intake and KOA still remain unclear. To identify the relationship between food intake and KOA and to screen relevant targets. First, we performed two-sample Mendelian randomization (MR) analysis. A total of 16 kinds of food intake datasets were included, the inverse variance-weighted analysis showed that the KOA was negatively correlated with cereal intake (odds ratio (OR) 0.48; 95% CI 0.35–0.68; P = 1.98 × 10?5). Second, potential drug targets of KOA in plasma were explored, secreted protein acidic and rich in cysteine (SPARC, or osteonectin), SPARC, Cwcv, and Kazal-like domains proteoglycan 2 (SPOCK2) as the causal protein for plasma with KOA, and increased SPOCK2 (OR 0.84; 95% CI 0.77–0.92; P = 5.52 × 10?5), decreased the risk of KOA. Integrated transcriptomic analysis (P = 0.028 5) and in vivo (P = 0.039 5) showed consistent results. Finally, by metabolomics analysis and molecular docking, seven co-expressed small molecules were detected in cereal and were bound to SPOCK2. Our findings indicate the cereal intake was negatively correlated with KOA, and support the SPOCK2 as a novel potential target for cereal intake in KOA. Our study will provide a clinical dietary guidance for KOA patients and a theoretical basis for the development of novel, side-effect-free drugs for KOA.

內(nèi)容: Alzheimer’s disease (AD) is a common neurodegenerative disease, and oxidative stress induced by amyloid β-protein (Aβ) deposition is the key cause of neuronal apoptosis in AD patient. Hydroxy-α-sanshool (HAS) is the predominant flavour substances in the pericarp of Zanthoxylum bungeanum Maxim. (Rutaceae family), which is a known condiment food and herbal medicine in China. We attempt to comprehensively elucidate the pathway and related mechanisms of HAS therapy on AD through in vivo and in vitro experiments. The results showed that HAS could inhibit cell apoptosis, suppress the reactive oxygen species (ROS), and increase the antioxidative enzymes in Aβ1–42 induced HT22 cells. In vivo, HAS attenuated the learning and memory impairment in senescence-accelerated mouse prone 8 (SAMP8) mice, and protected neuronal cells in hippocampus. Interestingly, the 16S rRNA gene sequencing results showed HAS could restore the richness and diversity of the intestinal microbiota, reduce the abundance of Lactobacillus, and increase the abundance of Bateroides and Parabacteroides. Moreover, the contents of 10 metabolites were significantly changed after HAS treatment, which was beneficial to treat AD. In conclusion, HAS could inhibit apoptosis in nerve cells by attenuating Aβ induced oxidative stress level, while it can also influence the metabolic pathways and affect the gut microbiota composition of AD mice.

內(nèi)容: Inonotus obliquus, an edible and medicinal fungus, has proven to be beneficial for relieving body aging. Previous research has shown that I. obliquus polysaccharide (IOP) can effectively reduce oxidative stress and alleviate photoaging in UVB-treated HaCaT cells. However, the underlying mechanism is still unclear. This study aimed to investigate the mechanism through which IOP mitigates skin photodamage by modulating mitochondrial autophagy through both in vivo and in vitro experiments. The results indicated that IOP alleviated the thickening of the stratum corneum and inflammatory infiltration caused by UVB radiation. Moreover, IOP effectively inhibited the mRNA expression of matrix metalloproteinase-1, 3 (MMP1 and MMP3) to prevent collagen breakdown and decreased the expression of aging-related proteins (P53 and P21) and inflammatory factors (tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in UVB-induced mice. Both in vitro and in vivo studies demonstrated that IOP increased Sirtuin3 (Sirt3) expression, activated the Foxo3a/PINK1-Parkin pathway and enhanced mitochondrial autophagy to reduce photodamage. Additionally, IOP could regulate the gut microbes in photodamaged mice and increase the relative abundance of Clostridium_XlVa, Desulfovibrio, and Barnesiella, which are important for protecting the intestinal barrier and alleviating intestinal dysfunction. These results provide a theoretical foundation for the use of IOP as a natural component to reduce skin photodamage.

內(nèi)容: Acetaminophen (APAP) used as an antipyretic and analgesic agent can cause acute liver injury (AILI) under overdose. Sanghuangporous vaninii is an edible fungus with abundant metabolites exhibits excellent hepatoprotective activities, but the effect for AILI is not yet fully understood. In this study, the polyphenolrich extract from S. vaninii (PSV) was prepared, with a total phenolic content of 75.72% and 34 compounds. The data of hepatoprotection indicated that PSV obviously alleviated the hepatocellular injury induced by APAP in vivo and in vitro. The protective mechanism of PSV against APAP-induced AILI might be attributed to the activating NRF2/GPX4 pathway. Based on network pharmacology analysis, the active components of PSV such as caffeic acid, osmundacetone and hispolone played a key role in hepatoprotection of PSV. Consequently, this study highlights the protection of PSV on AILI, which provides new insight into bioactivities of S. vaninii.

內(nèi)容: Nicotine, ethanol, and caffeine are the most common exogenous substances in the men’s living environment, but their effects on the cartilage quality in the father and offspring have not been reported. According to the average daily intake of adult men, we constructed a male rat model of paternal mixed exposure (PME) to low-dose nicotine (0.1 mg/(kg·day)), ethanol (0.5 g/(kg·day)), and caffeine (7.5 mg/(kg·day)) for 8 weeks. Then, the male rats mated with normal female rats to obtain offspring. The results showed that PME reduced the cartilage quality of paternal and offspring rats. Among them, the paternal cartilage was damaged by enhancing matrix degradation, while the offspring cartilage was damaged by reducing matrix synthesis. The cartilage damage in male offspring rats was more evident than in female offspring. It was further confirmed that differential GC regulation mechanisms were the main reasons for the intergenerational differential damage of paternal/offspring cartilage quality caused by PME. In addition, the androgen receptor (AR) and estrogen receptor beta (ERβ) mediated the sex difference of PME-induced fetal cartilage dysplasia by affecting the binding degree of GR/P300. This study provided a theoretical and experimental basis for guiding male healthy lifestyle and exploring early prevention and treatment strategies for paternal diseases.

內(nèi)容: Partridge tea (Mallotus oblongifolius Muell-Arg), an important and widely consumed substitute tea in Hainan, China, possessed multi-biological activities. This study investigated the composition and content of phenolics-rich extracts purified from partridge tea, and then explored the effect of partridge tea polyphenol extract (PTE) on glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) mice. The results showed that the dominant components in PTE included rutin ((63.78 ± 1.86) mg/g), 3-chlorogenic acid ((85.81 ± 3.48) mg/g), caffeic acid ((152.78 ± 2.93) mg/g), catechin ((12.10 ± 1.41) mg/g), gallic acid ((5.24 ± 0.12) mg/g), kaempferitrin, ellagic acid, ferulic acid, caffeic acid methylester, and geraniin. After 6 weeks of PTE intervention, glucose tolerance, insulin resistance, and pancreatic β-cell function in T2DM mice had significantly improved. This improvement was corroborated by an increase in glucagon-like peptide-1 (GLP-1) to homeostasis model assessment of β-cell function (HOMA-β), glycogen, insulin protein expression, and reduction in insulin levels, glycosylated serum protein (GSP), homeostasis model assessment-insulin resistance index (HOMA-IR), glucagon protein expression. The supplementation of PTE also seems to alleviate the inflammatory response, as evidenced by a decrease in endotoxin and inflammatory cytokine levels. Hyperglycemia-induced mitochondrial damage is alleviated by PTE intervention. Hematoxylin-eosin staining (H&E staining) and lipid profile analysis indicate that PTE intervention can help regulate lipid metabolism disorders. In addition, the integration of metabolomics and transcriptomic analysis indicates that PTE intervention could regulate glycolipid metabolism pathways related to T2DM, including insulin, AMPK, bile acid metabolism and glutathione metabolism signaling pathways. More importantly, the validation results from reverse transcription-polymerase chain reaction (RT-PCR) confirmed that the expressions of Scd1, Fasn, Hmgcr, and Slc2a4 (related to glycolipid metabolism) were consistent with the transcriptomics data. In conclusion, these results suggested that PTE may exhibit significant health promoting effects for T2DM mice.

內(nèi)容: Addressing the uncontrolled spread and increase in antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) will require new control strategies, particularly to improve the safety of food. Our results revealed the efficacy of theaflavin-3,3′-digallate (TFBG), which is a novel polyphenol derived from tea, in targeting the key regulatory protein multiple gene regulator A (MgrA) in S. aureus. Through fluorescence anisotropy, we showed that the half maximal inhibitory concentration (IC50) of TFBG was 26.76 μg/mL. TFBG uniquely counters S. aureus by regulating its virulence factors and adhesion processes rather than by killing the bacteria directly. This compound alters the expression of key virulence factors and modulates the transcription levels of genes related to adhesion in S. aureus, ultimately reducing the bacteria’s ability to adhere to fibrinogen and its hemolytic activity. Our assays confirmed that TFBG directly interacts with the MgrA protein in MRSA, and we identified critical binding sites. Our in vivo studies highlighted the potent efficacy of TFBG. TFBG administration is an innovative approach to improve food safety by diminishing MRSA virulence and reducing its pathogenicity.