PHYTOMEDICINE
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2024
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IF 6.7
Wang Yi,Jiang Yu,Li Mingxing,Xiao Yaqin,Zhao Qianyun,Zeng Jiuping,Wei Shulin,Chen Shuhan,Zhao Yueshui,Du Fukuan,Chen Yu,Deng Shuai,Shen Jing,Li Xiaobing,Li Wanping,Wang Fang,Sun Yuhong,Gu Li,Xiao Zhangang,Wang Shengpeng,Wu Xu
Background Rosavin (RSV) is a naturally occurring compound isolated from Rhodiola species. While RSV has been reported with pharmacological activities of anti-oxidation, anti-inflammation, anti-stress and immunomodulation, its effect on colitis and the underlying mechanisms remain unclear. Purpose This study aims to investigate whether and how RSV alleviated colitis in mice. Study design and methods The protective effect of RSV (50, 100, 200 mg/kg, p.o.) was investigated in dextran sulfate sodium (DSS) mediated mouse models of acute and chronic colitis. Alterations in fecal microbiota were evaluated by 16S rRNA sequencing. Pseudo germ-free mice achieved by antibiotics treatment were applied to assess the RSV-mediated functional role of gut microbiota in colitis. RNA sequencing was performed to determine RSV-induced colonic response. Primary T cell culture was conducted to examine the effect of RSV on Th17 and Treg differentiation. Whole blood assay, dual luciferase reporter assay, and molecular docking methods were applied to investigate the mechanisms and targets of RSV in Th17 regulation. Results Oral RSV significantly relieved DSS-mediated acute and chronic colitis in mice, which recovered body weight loss, reduced disease activity index, alleviated colon injury, inhibited inflammation, suppressed the apoptosis of intestinal epithelia, and maintained intestinal barrier function. Moreover, RSV specifically regulated intestinal microbiota by recovering DSS-mediated microbial changes and elevating beneficial microbes such as Lactobacillus and Akkermansia . Antibiotics treatment experiment showed that the protective role of RSV was at least partially dependent on gut microbiota; however, in vitro incubation showed that RSV did not directly promote the growth of Lactobacillus and Akkermansia strains. Further analysis showed that RSV-mediated genetic alterations in colon were enriched in pathways related to lymphocyte regulation. Additionally, RSV regulated the balance of Th17/Treg in colitis mice. Importantly, RSV inhibited the differentiation of Th17 cell in vitro , suppressed the production of IL-17 by Th17 cells, and downregulated Rorc encoding RORγt and its downstream Il17 . RSV significantly inhibited the RORγt transcription activity and bound to its ligand binding domain. Conclusion RSV alleviates murine colitis through regulating intestinal immunity. Notably, RSV is identified as a novel regulator of Th17 cells that inhibits RORγt-mediated Th17 differentiation. These findings potentiate the Rhodiola -derived natural chemicals as novel anti-colitis agents.
研究领域:
药理学
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免疫学
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微生物学
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分子生物学
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DOI
高影响因子
Food Bioscience
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2024
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IF 4.8
Zhikun Zeng,Hangyu Huang,Lin Wang,Yaqing Lin,Binbin Wang,Baodong Zheng,Yi Zhang,Lei Pan
Dictyophora indusiata is a nutritious edible mushroom, which polysaccharide exhibited a variety of biological activities. In this study, the digestion properties of steam-exploded Dictyophora indusiata polysaccharide (DIPS) were investigated by dynamic in vitro stomach-intestine digestive system. Here, the molecular weight of DIPS significantly was decreased and the microscopic surface structure appeared to be loose after 90 min of simulated stomach digestion. Interestingly, the molecular weight of DIPS was restored during the small intestine digestion phase, which was not significantly different compare with DIPS before stomach digestion, the functional groups, thermal stability and antioxidant properties of DIPS remained stable after digestion. It is remarkable that DIPS after dynamic in vitro stomach-intestine digestion regulated the composition of the gut microbiota, including Blautia , Megamonas , Parabacteroides and Phascolarctobacterium . In addition, DIPS promoted the level of acetic acid, propionic acid and butyric acid during the in vitro fermention, which were 2.42, 4.36 and 9.17 folds higher than controls, respectively. This study provides important significance for exploring the effects of edible mushroom polysaccharide on gut health.
研究领域:
食品科学
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微生物学
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营养学
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DOI
高影响因子
CNS Neuroscience & Therapeutics
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2022
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IF 7.035
Jing Li,Jianhao Liang,Meiqin Zeng,Kaijian Sun,Yunhao Luo,Huaping Zheng,Feng Li,Wen Yuan,Hongwei Zhou,Junshan Liu,Haitao Sun
Introduction White matter injury (WMI) significantly affects neurobehavioral recovery in intracerebral hemorrhage (ICH) patients. Gut dysbiosis plays an important role in the pathogenesis of neurological disorders. Oxymatrine (OMT) has therapeutic effects on inflammation-mediated diseases. Whether OMT exerts therapeutic effects on WMI after ICH and the role of gut microbiota involved in this process is largely unknown. Methods Neurological deficits, WMI, gut microbial composition, intestinal barrier function, and systemic inflammation were investigated after ICH. Fecal microbiota transplantation (FMT) was performed to elucidate the role of gut microbiota in the pathogenesis of ICH. Results OMT promoted long-term neurological function recovery and ameliorated WMI in the peri-hematoma region and distal corticospinal tract ( CST ) region after ICH. ICH induced significant and persistent gut dysbiosis, which was obviously regulated by OMT. In addition, OMT alleviated intestinal barrier dysfunction and systemic inflammation. Correlation analysis revealed that gut microbiota alteration was significantly correlated with inflammation, intestinal barrier permeability, and neurological deficits after ICH. Moreover, OMT-induced gut microbiota alteration could confer protection against neurological deficits and intestinal barrier disruption. Conclusions Our study demonstrates that OMT ameliorates ICH-induced WMI and neurological deficits by modulating gut microbiota.
研究领域:
神经病学
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肠道微生物学
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分子药理学
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神经免疫学
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转化医学
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DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2024
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IF 6.8
Qian-Wen Zhang,Meng-Jiao Yang,Chun-Yu Liao,Reham Taha,Qing-Yu Li,Mohammed Ismail Abdelmotalab,Si-Yu Zhao,Yan Xu,Zhen-Zhou Jiang,Cheng-Han Chu,Xin Huang,Chun-Hua Jiao,Li-Xin Sun
Background and Purpose Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study. Experimental Approach PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis. Key Results PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance. Conclusion and Implications Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.
研究领域:
免疫学
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微生物学
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药理学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Liyi Wei,Cuiping Qi,Tingting Wang,Xiuping Jin,Xinli Zhou,Mingcui Luo,Mengxi Lu,Huijun Chen,Juanjuan Guo,Hui Wang,Dan Xu
Amoxicillin is a widely used antibiotic globally, and its pervasive environmental presence poses significant risks to human health and ecosystems. Notably, prenatal amoxicillin exposure (PAmE) may have long-term neurodevelopmental toxicity for offspring. In this study, we investigated the lasting effects of PAmE on depressive-like behaviors in offspring rats, emphasizing the biological mechanisms mediated by changes in gut microbiota and its metabolite, myristic acid. Our results showed that PAmE significantly disrupted the gut microbiota composition in offspring, particularly through the reduction of Lachnospiraceae , leading to decreased levels of myristic acid. This disruption hindered the N-myristoylation of ADP-ribosylation factor 1 (ARF1), impaired the normal degradation of the stimulator of interferon genes protein, inhibited autophagic processes, and promoted M1 polarization of microglia, ultimately leading to depressive-like behaviors in the offspring. Remarkably, supplementation with Lachnospira or myristic acid effectively reversed the PAmE-induced neurodevelopmental and behavioral abnormalities, alleviating depressive-like symptoms. This study reveals how PAmE affects offspring neurodevelopment and behavior through gut microbiota and myristic acid, highlighting the crucial role of the gut-brain axis in the modulation of depressive symptoms. Supplementing Lachnospira or myristic acid could represent a novel strategy to mitigate PAmE-induced fetal-originated depression, providing new biological evidence and potential therapeutic avenues.
研究领域:
药理学
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神经科学
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微生物学
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行为科学
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分子生物学
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DOI
PubMed
高影响因子
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