学術雑誌リスト

This study investigated the potential benefits of black chokeberry polyphenol (BCP) supplementation on lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 cells and obesity-induced colonic inflammation in a high fat diet (HFD)-fed rat model. Our findings demonstrated that BCP treatment effectively reduced the production of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1) in LPS-induced RAW264.7 cells and concurrently mitigated oxidative stress by modulating the levels of malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px) in a dose-dependent manner. Furthermore, BCP supplementation significantly ameliorated HFD-induced obesity, improved glucose tolerance, and reduced systemic inflammation in HFD-fed rats. Notably, BCP treatment suppressed the mRNA expression of pro-inflammatory cytokines and alleviated intestinal barrier dysfunction by regulating the mRNA and protein expression of key tight junction proteins (ZO-1, occludin, and claudin-1), thereby inhibiting colonic inflammation caused by the TLR4/NF-κB signaling pathway. Additionally, BCP treatment altered the composition and function of the gut microbiota, leading to an increase in the total content of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, isobutyric acid, and butyric acid. Collectively, our results highlighted the potential of BCP supplementation as a promising prebiotic strategy for treating obesity-induced colonic inflammation.

Over the past few decades, osteoarthritis (OA) has been a major health problem worldwide. It is urgent to develop new, effective, and safe drugs to treat OA. There are many pentacyclic triterpenoids in nature that are safe and have health benefits. Oleanolic acid (OLA), one of the pentacyclic triterpenoids, is a potential novel compound for treating OA; however, its mechanism of action is still unclear. In this study, the mechanism of resistance to extracellular matrix (ECM) degradation of OLA and its protective role in the amelioration of OA were investigated by in vivo and in vitro experiments. We found that OLA promoted interleukin-1β (IL-1β)-induced production of type II collagen (collagen II) in rat chondrocytes, decreased the expression of matrix metalloproteinase (MMP)-3 and MMP-13, and inhibited inflammatory cytokine (IL-1β and TNF-α) and cartilage marker (CTX-II and COMP) levels, thereby hindering the pathological process of cartilage. Mechanistically, OLA inhibited the Wnt/β-catenin pathway, activated the Hippo/YAP pathway, and hampered the ECM degradation process by inhibiting the nuclear translocation of β-catenin and YAP. When we knocked down β-catenin, OLA lost its stimulatory effect on the Hippo pathway. These findings confirm that OLA plays an anti-ECM degradation role by regulating the Wnt/β-catenin and Hippo/YAP pathways. Overall, this study provides a theoretical basis for developing highly effective and low-toxic natural products for the prevention and treatment of OA.

Flavonoids often exhibit broad bioactivity but low solubility and bioavailability, limiting their practical applications. The transglycosylated materials α-glucosyl rutin (Rutin-G) and α-glucosyl hesperidin (Hsp-G) are known to enhance the dissolution of hydrophobic compounds, such as flavonoids and other polyphenols. In this study, the effects of these materials on flavone solubilization were investigated by probing their interactions with flavone in aqueous solutions. Rutin-G and Hsp-G prepared via solvent evaporation and spray-drying methods were evaluated for their ability to dissolve flavones. Rutin-G had a stronger flavone-solubilizing effect than Hsp-G in both types of composite particles. The origin of this difference in behavior was elucidated by small-angle X-ray scattering (SAXS) and nuclear magnetic resonance analyses. The different self-association structures of Rutin-G and Hsp-G were supported by SAXS analysis, which proved that Rutin-G formed polydisperse aggregates, whereas Hsp-G formed core–shell micelles. The observation of nuclear Overhauser effects (NOEs) between flavone and α-glucosyl materials suggested the existence of intermolecular hydrophobic interactions. However, flavone interacted with different regions of Rutin-G and Hsp-G. In particular, NOE correlations were observed between the protons of flavone and the α-glucosyl protons of Rutin-G. The different molecular association states of Rutin-G or Hsp-G could be responsible for their different effects on the solubility of flavone. A better understanding of the mechanism of flavone solubility enhancement via association with α-glucosyl materials would permit the application of α-glucosyl materials to the solubilization of other hydrophobic compounds including polyphenols such as flavonoids.

Veillonella and Lactobacillus species are key regulators of a healthy gut environment through metabolic cross-feeding, influencing lactic acid and short-chain fatty acid (SCFA) levels, which are crucial for gut health. This study aims to investigate how Veillonella ratti (V. ratti) and Lactobacillus acidophilus (LA) interact with each other and alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in a mouse model. We assess their metabolic interactions regarding carbon sources through co-culturing in a modified medium. In the in vitro experiments, V. ratti and LA were inoculated in mono-cultures and co-culture, and viable cell counts, OD600, pH, lactic acid, glucose and SCFAs were measured. For the in vivo experiment, 60 C57BL/6 mice were randomly divided into five groups and administered V. ratti and LA alone or in combination via oral gavage (1 × 109 CFU mL−1 per day per mouse) for 14 days. On the seventh day, 2.5% DSS was added to the drinking water to induce colitis. The effects of these probiotics on UC were evaluated by assessing intestinal barrier integrity and intestinal inflammation in the gut microenvironment. In vitro results demonstrated that co-culturing V. ratti with LA significantly increased viable cell numbers, lactic acid production, and SCFA production, while reducing pH and glucose levels in the medium. In vivo findings revealed that intervention with V. ratti, particularly in combination with LA, alleviated symptoms, including weight loss, colon shortening, and tissue damage. These probiotics mitigated intestinal inflammation by down-regulating pro-inflammatory molecules, such as IL-6, IL-1β, IL-γ, iNOS, and IFN-γ, as well as oxidative stress markers, including MDA and MPO. Concurrently, they upregulated the activity of anti-inflammatory enzymes, namely, SOD and GSH, and promoted the production of SCFAs. The combined intervention of V. ratti and LA significantly increased acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in cecal contents. Furthermore, the intervention of V. ratti and LA increased the abundance of beneficial bacteria, such as Akkermansia, while reducing the abundance of harmful bacteria, such as Escherichia–Shigella and Desulfovibrio, thereby mitigating excessive inflammation. These findings highlight the enhanced therapeutic effects resulting from the interactions between V. ratti and LA, demonstrating the potential of this combined probiotic approach.

Over the past few decades, food allergy has continued to rise, significantly affecting our health, economy, and quality of life. However, current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies is to modulate immunity and microbiota. Human milk (HM) could be considered a protective factor against food allergy, but how probiotics in human milk impact the susceptibility to food allergy remains unknown. Therefore, we studied the preventive impact of human milk Lactobacillus rhamnosus Probio-M9 on food allergy in ovalbumin (OVA)-sensitized mice. We studied the effects of oral administration of Probio-M9 on allergic signatures, immune response, gut microbiota, and metabolism. Oral therapeutic administration of live Probio-M9, but not heat-killed Probio-M9, significantly reduces OVA-specific IgE (OVA-sIgE), histamine, and mMCP-1 (mouse mast cell protease-1) levels in OVA-sensitized mice. Moreover, Probio-M9 supplementation reduced allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response. 16S rDNA sequencing analysis revealed an increased ratio of Firmicutes/Bacteroidota (F/B) and the relative abundance of short-chain fatty acid (SCFA)-producing Clostridia in the feces after Probio-M9 intake. Simultaneously, Probio-M9 significantly increased the levels of SCFAs and promoted the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inducing the expression of the antimicrobial peptides (AMPs) Reg3b and Reg3g. Our findings suggest that the use of Probio-M9 can be a potent strategy in food allergy prevention.

Previous studies have found that chitosan oligosaccharide (COST) can alleviate the clinical symptoms in non-alcoholic fatty liver disease (NAFLD) patients. We intend to intervene with different concentrations of COST in mice with NAFLD induced by a high fat diet. The basic effect of COST on NAFLD model mice was observed using physiological and biochemical indexes. 16S rRNA sequencing technology was used to analyze the gut microbiota and further analyze the content of short-chain fatty acids (SCFAs). Western blot and RT-PCR were used to detect the effects of COST on the PI3K/AKT/mTOR signaling pathway in the livers of NAFLD mice. It was found that the COST-high-dose group could reduce the weight of NAFLD mice, improve dyslipidemia, and alleviate liver lesions, and COST has a therapeutic effect on NAFLD mice. 16S rRNA sequencing analysis showed that COST could increase the diversity of the gut microbiota in NAFLD mice. The downregulation of SCFAs in NAFLD mice was reversed. WB and RT-PCR results showed that the PI3K/AKT/mTOR signaling pathway was involved in the development of NAFLD mice. COST improved liver lipid metabolism in NAFLD mice by inhibiting liver DNL. COST could increase the expression of thermogenic protein and UCP1 and PGC-1α genes; the PI3K/AKT/mTOR signaling pathway is inhibited at the protein and gene levels. This study revealed that COST regulates the expression of related inflammatory factors caused by lipid toxicity through the gut microbiota and SCFAs, and improves the liver lipid metabolism of HFD-induced NAFLD mice, laying a foundation for the development of effective and low toxicity drugs for the treatment of NAFLD.

Green tea is one of the main types of tea in China, and it has been widely consumed in the world. This study aims to investigate the potential mechanism by which the water extract of green tea (GTWE) may be effective in the treatment of alcohol-related hepatitis (ARH), utilizing a combination of network pharmacology, molecular docking, and experimental validation. Through network pharmacology analysis, seven active components and 45 potential targets were identified, with TLR4 being confirmed as the central target. Experimental findings demonstrate that GTWE exhibits significant efficacy in mitigating alcohol-induced liver inflammation and steatosis. Furthermore, the administration of GTWE has demonstrated significant efficacy in mitigating alcohol-induced intestinal inflammation and microbiota disturbance while concurrently restoring intestinal barrier function. Consequently, GTWE exhibits considerable potential as a pharmacological intervention and warrants further research and development as a lead compound for the treatment of ARH. Moreover, the prospective utilization of green tea in prolonged intakes exhibits potential as a prophylactic nutritive regimen against ARH.

Individuals with rotating and night shift work are highly susceptible to developing metabolic disorders such as obesity and diabetes. This is primarily attributed to disruptions in the circadian rhythms caused by activities and irregular eating habits. Time-restricted feeding (tRF) limits the daily eating schedules and has been demonstrated to markedly improve several metabolic disorders. Although an intricate relationship exists between tRF and circadian rhythms, the underlying specific mechanism remains elusive. We used a sleep disruption device for activity interference and established a model of circadian rhythm disorder in mice with different genetic backgrounds. We found that circadian rhythm disruption led to abnormal hormone secretion in the gut and elevated insulin resistance. tRF improved metabolic abnormalities caused by circadian rhythm disruption, primarily by restoring the gut hormone secretion rhythm and activating brown fat thermogenesis. The crucial function of brown fat in tRF was confirmed using a mouse model with brown fat removal. We demonstrated that chenodeoxycholic acid (CDCA) effectively improved circadian rhythm disruption-induced metabolic disorders by restoring brown fat activation. Our findings demonstrate the potential benefits of CDCA in reversing metabolic disadvantages associated with irregular circadian rhythms.

Purpose: The development of hypertension is shown to be triggered by chronic low-grade inflammation. The dietary inflammatory index (DII) is a parameter for assessing the potential of a diet to cause inflammation. The prospective association between the DII and new-onset hypertension in Chinese adults remains unclear. Materials and methods: The nationwide cohort study included 10694 participants from 7 rounds of the China Health and Nutrition Survey. Dietary nutrient intake data were collected by 3-day 24 h dietary recalls and used to calculate the DII. The time-dependent Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for studying the risk of new-onset hypertension, and stratified analyses were used to examine factors that may modify the association. Restricted cubic spline (RCS) regression was used to examine the non-linear relationship between the DII and new-onset hypertension. The relationship between the DII and physical activity was analyzed with the time-dependent Cox regression model. Results: The highest quartile of the DII had a significantly higher risk of new-onset hypertension compared to the lowest quartile (adjusted HR, 1.13; 95% CI, 1.02, 1.24). RCS regression results showed that the risk of new-onset hypertension increased significantly after the DII above 1.09 (P for non-linearity <0.001). The interaction results showed that the DII may play a better role (P < 0.05) in the female, age < 45 years, baseline SBP < 130 mmHg, DBP < 80 mmHg, BMI < 24 kg m−2 and moderate/heavy physical activity level subgroup. Stratified analysis results showed that the baseline SBP, DBP, obesity, and physical activity level modified the association between the DII and hypertension (P for interaction < 0.05). Conclusion: Reducing the inflammatory potential of the diet is an effective strategy to prevent hypertension in Chinese adults.

Herein, we studied the in vitro-simulated intestinal flora fermentation of Porphyra haitanensis polysaccharides (PHPs) with microwave, ultrasonic, ultra-high pressure-assisted extraction and the protective effect of their fermented products against HT-29 human colon cancer cells. The results showed that PHPs were largely degraded at the 18 h stage of ascending colon fermentation, further greatly increasing the contents of reducing sugars and short-chain fatty acids (p < 0.05). Particularly, the PHPs subjected to ultra-high pressure-assisted extraction (UHP-PHP) showed the highest reducing sugar content of 1.68 ± 0.01 mg mL−1 and butyric acid content of 410.77 ± 7.99 mmol mL−1. Moreover, UHP-PHP showed a better effect in increasing the ratio of Bacteroidetes/Firmicutes and decreasing the abundance of Proteobacteria and Escherichia coli. PHPs could protect against HT-29 cells by increasing the ROS levels in a concentration-dependent manner, especially UHP-PHP fermented in a descending colon for 24 h. This was related to the up-regulated apoptosis-related genes (Bax and Bak), down-regulated protein expression of Bcl-2 and activation of the p-AKT protein, thereby promoting the apoptosis of HT-29 cells. Our results can facilitate the modification of PHPs and their practical application in the development of intestinal health improving products.