Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy ...Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy of Scytosiphon lomentaria fucoidan(SLF)in alleviating alcohol-induced liver injury was evaluated in a mouse model.It showed that SLF increased body weight and colon length,while reducing liver index,serum lipid,alanine aminotransferase,and aspartate aminotransferase in alcohol-treated mice.SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines.It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway.SLF modulated alcohol-induced dysbiosis of gut microbiota,including a reduction in Bacteroidetes and Proteobacteria,and improved metabolites profile,primarily affecting short chain fatty acids and amino acids metabolism.In addition,SLF reduced the level of total bile acids,regulated the profile of bile acids,and increased the levels of farnesoid X receptor(FXR)and AMP-activated protein kinase(AMPK),suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway.This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.展开更多
法尼醇X受体(Farnesoid X Receptor,FXR)属于代谢性核受体,是需配体激活的转录因子,在肝脏胆汁酸、脂质代谢过程,肝脏炎症和肿瘤的发展过程中起着重要的调节作用。小异二聚体伴侣受体(Small Heterodimer Partner,SHP)是核受体超家族中...法尼醇X受体(Farnesoid X Receptor,FXR)属于代谢性核受体,是需配体激活的转录因子,在肝脏胆汁酸、脂质代谢过程,肝脏炎症和肿瘤的发展过程中起着重要的调节作用。小异二聚体伴侣受体(Small Heterodimer Partner,SHP)是核受体超家族中的一个特殊成员,在特异的组织中作为转录调节的共抑制因子,抑制其他多种转录因子的活性,在众多代谢通路中起到了负性调节作用。近年来研究发现,核受体FXR通过对SHP的调控来实现其在肝脏的多种功能。本文着重对FXR调节SHP的机制及FXR-SHP轴在肝脏中作用进行综述。展开更多
Shuiman tea,a unique variant of Pu-erh tea,contains polysaccharides known for their antioxidant and hypoglycemic activities.However,their anti-obesity potential remains unexplored.In this study,a homogeneous acidic po...Shuiman tea,a unique variant of Pu-erh tea,contains polysaccharides known for their antioxidant and hypoglycemic activities.However,their anti-obesity potential remains unexplored.In this study,a homogeneous acidic polysaccharide,STPS-3-1,was successfully isolated from Shuiman tea,and its preliminary structure and digestion characteristics were comprehensively analyzed.After 12 weeks of STPS-3-1 intervention,high-fat diet(HFD)-induced male C57BL/6J mice(specific pathogen free(SPF)grade,6 weeks old,18–20 g)exhibited significant metabolic improvements,including improved blood glucose and lipid levels,mitigated metabolic disorders,and reduced inflammation.Furthermore,STPS-3-1 notably reshaped the gut microbiota,enriching key species such as Bacteroides vulgatus.Subsequently,the B.vulgatus LWZ 240601 strain was successfully isolated and identified.This strain efficiently degraded STPS-3-1 under the synergistic action of three polysaccharide utilization loci(PULs),producing metabolites that regulated bile acid(BA)metabolism through the FXR/SHP signaling pathway,significantly alleviating obesity-related symptoms in antibiotic(ABX)-treated mice.This study provides valuable insights into the metabolic regulatory mechanisms and anti-obesity potential of STPS-3-1,elucidating their probiotic effects through gut microbiota modulation.Additionally,it expands the potential of tea polysaccharides in gut microbiota modulation and metabolic disease intervention,supporting the development of plant-based functional foods.展开更多
The 3,5-dicaffeoylquinic acid(3,5-DiCQA),a key component of Chuzhou chrysanthemum,one of the“Four Major Edible Chrysanthemums”in China,has been shown to enrich beneficial gut bacteria and reduce lipid synthesis base...The 3,5-dicaffeoylquinic acid(3,5-DiCQA),a key component of Chuzhou chrysanthemum,one of the“Four Major Edible Chrysanthemums”in China,has been shown to enrich beneficial gut bacteria and reduce lipid synthesis based on its hydroxycinnamic acid structures.However,its low lipophilicity limits bioactivity,necessitating the development of more stable derivatives.Therefore,this study synthesized and characterized a novel esterified derivative 3,5-DiCQA dodecyl ester(3,5-DiCQAD)with markedly enhanced lipophilicity and bioactivity.In highfat diet(HFD)-induced male C57BL/6J mice,3,5-DiCQAD showed remarkable metabolic regulatory effects,including improvements in glucose metabolism,lipid homeostasis,BA signaling,and thermogenesis.Furthermore,3,5-DiCQAD effectively reshaped the gut microbiota,enriching beneficial bacteria such as Lactobacillus plantarum.Moreover,the strain L.plantarum ZZ 240321 was isolated,and its fermentation of 3,5-DiCQAD generated metabolites that modulated bile acid(BA)metabolism through the FXR/SHP/LRH-1 pathway,alleviating obesity-related symptoms in antibiotic-treated mice.This research provides a novel perspective for developing plant-derived polyphenols as anti-obesity treatments.It also broadens the understanding of DiCQA’s probiotic potential in the gut microbiome,highlighting its promising role in managing metabolism-associated disorders.展开更多
目的:基于法尼醇X受体(farnesoid X receptor,FXR)/Takeda G蛋白偶联受体5(Takeda G protein-coupled receptor 5,TGR5)信号通路探讨厚朴三物汤调节胆囊切除术后兔胆汁组分的作用机制。方法:32只大耳白兔随机分为空白组、模型组、厚朴...目的:基于法尼醇X受体(farnesoid X receptor,FXR)/Takeda G蛋白偶联受体5(Takeda G protein-coupled receptor 5,TGR5)信号通路探讨厚朴三物汤调节胆囊切除术后兔胆汁组分的作用机制。方法:32只大耳白兔随机分为空白组、模型组、厚朴三物汤组及对照组,每组8只。模型组和厚朴三物汤组兔建立胆囊切除模型,术后次日开始灌胃,每日1次,连续4周。采用全自动生化分析仪检测胆汁中总胆红素(total bilirubin,TB)、直接胆红素(direct bilirubin,DB)、间接胆红素(undirect bilirubin,UCB)、总胆汁酸(total bile acid,TBA)含量,HE染色观察肝脏和回肠组织病理变化,IHC法检测肝脏和回肠组织中成纤维细胞生长因子19(fibroblast growth factor 19,FGF19)、胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)、胆汁酸结合蛋白(ileal bile acid binding protein,IBABP)、微小异源二聚体伙伴基因(small het erodimer partner gene,SHP)、胆固醇7α-羟化酶(cholesterol 7α-hydroxylase,CYP7A1)蛋白表达水平,RT-qPCR法检测肝和回肠组织中SHP、IBABP、CYP7A1、FGF19、GLP-1基因表达水平。结果:与空白组比较,模型组兔TB、UCB含量减少,TBA含量增加(P<0.01)。与模型组比较,厚朴三物汤组兔TB、UCB含量增加(P<0.05),TBA含量减少(P<0.01)。HE染色显示,空白组兔肝组织未见明显病理改变;对照组兔肝细胞饱满,胆管周围有炎症细胞浸润,肝小叶中央静脉扩张;模型组兔肝索排列紊乱,胆管周围少量炎症细胞浸润,肝小叶中央静脉轻度扩张,肝窦淤血。厚朴三物汤组兔肝组织结构相对完整,肝索排列相对整齐。与空白组比较,对照组与模型组兔回肠绒毛肿胀,数量减少,排列紊乱。与模型组比较,厚朴三物汤组兔回肠绒毛数量增加且排列整齐。IHC与RT-qPCR显示,与空白组比较,模型组兔肝脏和回肠组织中SHP、IBABP、FGF19、GLP-1表达水平升高,CYP7A1表达水平降低(P<0.01);与模型组比较,厚朴三物汤组兔肝脏和回肠组织中SHP、IBABP、FGF19、GLP-1表达水平降低,CYP7A1表达水平升高(P<0.05)。结论:厚朴三物汤可能通过抑制FXR/TGR5信号通路,调节胆汁酸水平,从而治疗胆囊切除术后综合征。展开更多
文摘Alcohol intake is associated with increased mortality worldwide,particularly liver diseases,making it imperative to explore innovative strategies for managing alcohol-related liver disease.In this study,t he efficacy of Scytosiphon lomentaria fucoidan(SLF)in alleviating alcohol-induced liver injury was evaluated in a mouse model.It showed that SLF increased body weight and colon length,while reducing liver index,serum lipid,alanine aminotransferase,and aspartate aminotransferase in alcohol-treated mice.SLF inhibited inflammatory response in the liver by reducing inflammatory infiltration and the levels of pro-inflammatory cytokines.It can be associated with the alleviation of oxidative stress and the inhibition of the nuclear factor-κB pathway.SLF modulated alcohol-induced dysbiosis of gut microbiota,including a reduction in Bacteroidetes and Proteobacteria,and improved metabolites profile,primarily affecting short chain fatty acids and amino acids metabolism.In addition,SLF reduced the level of total bile acids,regulated the profile of bile acids,and increased the levels of farnesoid X receptor(FXR)and AMP-activated protein kinase(AMPK),suggesting that SLF can alleviate alcohol-induced liver injury by regulating bile acid-FXR/AMPK pathway.This study suggests that SLF holds the potential to alleviate the adverse effect of alcohol on the liver via the gut-liver axis.
文摘法尼醇X受体(Farnesoid X Receptor,FXR)属于代谢性核受体,是需配体激活的转录因子,在肝脏胆汁酸、脂质代谢过程,肝脏炎症和肿瘤的发展过程中起着重要的调节作用。小异二聚体伴侣受体(Small Heterodimer Partner,SHP)是核受体超家族中的一个特殊成员,在特异的组织中作为转录调节的共抑制因子,抑制其他多种转录因子的活性,在众多代谢通路中起到了负性调节作用。近年来研究发现,核受体FXR通过对SHP的调控来实现其在肝脏的多种功能。本文着重对FXR调节SHP的机制及FXR-SHP轴在肝脏中作用进行综述。
基金supported by the National Natural Science Foundation of China(No.31901617)the National Key Research and Development Program of China(2017YFD0400600)+8 种基金the Top Talent Project of Department of Education of Anhui Province(gxyqZD2021125)the Excellent Talent project of Anhui Science and Technology University(XJYXRC202101)the Stable Talent Personnel Project of Anhui Science and Technology University(SPWD202101)the Natural Science Research Foundation of Department of Education of Anhui Province(2022AH040236)Project of Science and Technology Innovation Team of Anhui Science and Technology University(2023KJCXTD003)the Undergraduate Innovation and Entrepreneurship Training Program of Anhui Province(S202310879232)the Excellent Research and Innovation Team of Anhui Province Universities(2024AH010007)Discipline Leader Development Program of Anhui Province(DTR2024034)Anhui Province Youth Top Talent Scholar Program.
文摘Shuiman tea,a unique variant of Pu-erh tea,contains polysaccharides known for their antioxidant and hypoglycemic activities.However,their anti-obesity potential remains unexplored.In this study,a homogeneous acidic polysaccharide,STPS-3-1,was successfully isolated from Shuiman tea,and its preliminary structure and digestion characteristics were comprehensively analyzed.After 12 weeks of STPS-3-1 intervention,high-fat diet(HFD)-induced male C57BL/6J mice(specific pathogen free(SPF)grade,6 weeks old,18–20 g)exhibited significant metabolic improvements,including improved blood glucose and lipid levels,mitigated metabolic disorders,and reduced inflammation.Furthermore,STPS-3-1 notably reshaped the gut microbiota,enriching key species such as Bacteroides vulgatus.Subsequently,the B.vulgatus LWZ 240601 strain was successfully isolated and identified.This strain efficiently degraded STPS-3-1 under the synergistic action of three polysaccharide utilization loci(PULs),producing metabolites that regulated bile acid(BA)metabolism through the FXR/SHP signaling pathway,significantly alleviating obesity-related symptoms in antibiotic(ABX)-treated mice.This study provides valuable insights into the metabolic regulatory mechanisms and anti-obesity potential of STPS-3-1,elucidating their probiotic effects through gut microbiota modulation.Additionally,it expands the potential of tea polysaccharides in gut microbiota modulation and metabolic disease intervention,supporting the development of plant-based functional foods.
基金supported by the National Natural Science Foundation of China(No.31901617)the National Key Research and Development Program of China(2017YFD0400600)+8 种基金the Top Talent Project of Department of Education of Anhui Province(gxyqZD2021125)the Excellent Talent project of Anhui Science and Technology University(XJYXRC202101)the Stable Talent Personnel Project of Anhui Science and Technology University(SPWD202101)the Natural Science Research Foundation of Department of Education of Anhui Province(2022AH040236)Project of Science and Technology Innovation Team of Anhui Science and Technology University(2023KJCXTD003)the Undergraduate innovation and entrepreneurship training program of Anhui Province(202410879088)the Excellent Research and Innovation Team of Anhui Province(2024AH010007)Discipline Leader Development Program of Anhui Province(DTR2024034)Anhui Province Youth Top Talent Scholar Program.
文摘The 3,5-dicaffeoylquinic acid(3,5-DiCQA),a key component of Chuzhou chrysanthemum,one of the“Four Major Edible Chrysanthemums”in China,has been shown to enrich beneficial gut bacteria and reduce lipid synthesis based on its hydroxycinnamic acid structures.However,its low lipophilicity limits bioactivity,necessitating the development of more stable derivatives.Therefore,this study synthesized and characterized a novel esterified derivative 3,5-DiCQA dodecyl ester(3,5-DiCQAD)with markedly enhanced lipophilicity and bioactivity.In highfat diet(HFD)-induced male C57BL/6J mice,3,5-DiCQAD showed remarkable metabolic regulatory effects,including improvements in glucose metabolism,lipid homeostasis,BA signaling,and thermogenesis.Furthermore,3,5-DiCQAD effectively reshaped the gut microbiota,enriching beneficial bacteria such as Lactobacillus plantarum.Moreover,the strain L.plantarum ZZ 240321 was isolated,and its fermentation of 3,5-DiCQAD generated metabolites that modulated bile acid(BA)metabolism through the FXR/SHP/LRH-1 pathway,alleviating obesity-related symptoms in antibiotic-treated mice.This research provides a novel perspective for developing plant-derived polyphenols as anti-obesity treatments.It also broadens the understanding of DiCQA’s probiotic potential in the gut microbiome,highlighting its promising role in managing metabolism-associated disorders.
文摘为研究功效性米粉对高脂诱导小鼠高血脂症的防治作用,并探讨其作用机制,选取决明子、葛根、山药、薏苡仁、沙棘等药食同源原料,与荞麦和藜麦混合制成米粉,选取48只六周龄无特定病原体(specific pathogen free,SPF)级健康ICR雄性小鼠,采用高脂饲料构建高血脂模型,并在造模期间灌胃功效性米粉干预。检测每组小鼠体质量、肝质量变化,血清中甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)含量,以及血清、肝脏、粪便中总胆汁酸含量,肝脏组织中法尼酯X受体(farnesoid X receptor,FXR)蛋白、小异二聚体伴侣(small heterodimer partner,SHP)蛋白、细胞色素P450家族成员7A1(cytochrome P4507A1,CYP7A1)蛋白表达水平和肠道菌群结构以及多样性。结果表明,功效性米粉能有效降低高血脂小鼠血清TG、TC和LDL-C含量,提高HDL-C含量;降低血清和肝脏中总胆汁酸含量,提高粪便中总胆汁酸含量;同时下调肝脏中FXR、SHP蛋白的表达;提高肠道微生物的丰度和多样性,改善肠道菌群结构。因此,功效性米粉可以防治高脂诱导小鼠的高血脂症,调节肠道菌群,其机制可能与调节FXR-SHP通路和促进胆汁酸排泄有关。
