Apple polyphenols extract alleviated dextran sulfate sodium-induced ulcerative colitis in C57BL/6 male mice by restoring bile acid metabolism disorder and gut microbiota dysbiosis.

To investigate and compare the preventive effects of apple polyphenols extract (APE) with phloretin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), 60 male mice were treated with 125 or 500 mg/(kg bw d) APE or 100 mg/(kg bw d) phloretin, the single-ingredient of APE, for continuous 3 weeks by intragastric administration, meanwhile, mice were provided with 3% DSS dissolved in drinking water to induce UC during the third week. Both APE and phloretin significantly ameliorated DSS-induced UC by inhibiting body weight loss, preventing colon shortening and mucosa damage. Except the same mechanisms of the inhibited activation of NF-κB signaling, decreased hyodeoxycholic acid level and increased abundance of Verrucomicrobia at phylum and Bacteroides and Akkermansia at genus, APE increased β-muricholic acid level and decreased Bacterodetes abundance, while phloretin decreased Firmicutes abundance. Furthermore, APE treatment showed much lower disease activity index score, less body weight loss and lighter spleen than phloretin. Thus, our study supported the potentiality of APE as a promising dietary intervention for the prevention of experimental UC.

Liu F ，Wang X ，Li D ，Cui Y ，Li X ... -  《-》

Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.

Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.

Wu M ，Li P ，An Y ，Ren J ，Yan D ，Cui J ，Li D ，Li M ，Wang M ，Zhong G ... -  《-》

Painong-San extract alleviates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota, restoring intestinal barrier function and attenuating TLR4/NF-κB signaling cascades.

The intestinal barrier dysfunction and the gut microbiota dysbiosis with excessive progress of inflammation contribute to the occurrence and acceleration of ulcerative colitis (UC). Painong Powder, a traditional Chinese medicine prescription, consists of Aurantii Fructus Immaturus, Paeoniae Radix Alba and Platycodonis Radix, which has been found to defend against colitis, but it is unclear whether its role in preventing UC is related to gut microbiota. This study aims to evaluate the effects of Painong-San extract (PNS) on UC and reveals the mechanisms related to gut microbiota. Firstly, a total of 125 chemical compounds, including 42 flavonoids, 29 triterpenoids, 21 monoterpenoids, 11 polyphenols, 6 limonoids, 5 alkaloids, 4 coumarins and 7 other compounds, were identified from PNS using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then, the results in vivo studies demonstrated that PNS treatment reduced the weight loss and the disease activity index, prevented colon shortening and alleviated colonic tissue damage in dextran sulfate sodium (DSS)-induced colitis mice. The intestinal barrier damage was repaired after PNS administration through promoting the expression of tight junction proteins (claudin-1, occludin and zonula occludens-1). More interestingly, PNS regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria, such as Oscillospiraceae and Helicobacter, while the probiotic gut microbiota like Romboutsia, Lactobacillus, Bifidobacterium and Akkermansia were increased. Furthermore, PNS remarkably ameliorated colonic inflammatory response through inhibiting intestinal TLR4/NF-κB signaling pathway by down-regulating the protein expressions of TLR4, MyD88, p-NF-κB p65 and p-IκBα. Taken together, PNS effectively improved DSS-induced colitis through the modulation of gut microbiota, restoration of intestinal barrier function and attenuation of TLR4/NF-κB signaling cascades, which may provide a new explanation of the mechanisms of PNS against UC.

Wang K ，Guo J ，Chang X ，Gui S ... -  《-》

Apple Polyphenol Extract Improves High-Fat Diet-Induced Hepatic Steatosis by Regulating Bile Acid Synthesis and Gut Microbiota in C57BL/6 Male Mice.

Li D ，Cui Y ，Wang X ，Liu F ，Li X ... -  《-》

Total alkaloids of Sophora alopecuroides L. ameliorated murine colitis by regulating bile acid metabolism and gut microbiota.

Sophora alopecuroides L. is one of the most commonly used plants in traditional medicine for the management conditions including inflammatory and gastrointestinal disease. However, the therapeutic mechanism of Sophora alopecuroides L.particularly in inflammatory bowel disease (IBD) remains unclear. To evaluate the treatment effects of total alkaloids of Sophora alopecuroides L. in ulcerative colitis (UC) mice model and explore the therapeutic mechanism of KDZ on UC based on bile acid metabolism and gut microbiota. Colitis were induced in BALB/c mice by administering 3.5% dextran sulfate sodium (DSS) in drinking water for 7 days. The mice were then given KDZ (300, 150 and 75 mg/kg) and the positive drug sulfasalazine (SASP, 450 mg/kg) via oral administration for 7 days. The levels of 23 bile acids in the liver, bile, serum, cecum content and colon were determined through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The cecum microbiota was characterized through high-throughput Illumina MiSeq sequencing. KDZ treatment significantly decreased the disease activity index (DAI) scores and ameliorated colonic injury in DSS-treated mice. The expression of IL-1β and TGF-β1 were suppressed, yet, IL-10 was up-regulated by KDZ and SASP treatment compared with those in the model group. Meanwhile, the serum contents of total bile acid and total cholesterol in the DSS group increased significantly compared with those in the control group, but reversed by SASP and KDZ. The relative abundance of Firmicutes increased after KDZ was administration, whereas the abundance of Bacteroidetes decreased. αMCA, βMCA, ωMCA and CA in the SASP and KDZ groups did not differ from those in the control group, whereas these parameters significantly increased in the DSS group. KDZ had a protective effect on DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis and regulating bile acid metabolism.

Jia YQ ，Yuan ZW ，Zhang XS ，Dong JQ ，Liu XN ，Peng XT ，Yao WL ，Ji P ，Wei YM ，Hua YL ... -  《-》