Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived f...Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived from grapefruit which has a variety of biological activities.However,the precise mechanisms of nootkatone on NAFLD remains to be defined.Our results showed that nootkatone prevented body weight gain and decreased serum lipid level,hepatic lipogenesis,hepatic proinflammatory cytokines secretion in NAFLD mice.Also,nootkatone attenuated inflammatory response via inhibiting TLR4/NF-κB/NLRP3 pathway.Moreover,nootkatone restored intestinal barrier damage through increasing tight junction proteins and short chain fatty acids contents.Further 16S rRNA sequencing of colonic content suggested that nootkatone recovered the disturbed gut microbiota to improve NAFLD.Spearman correlation analysis between gut microbiota and NAFLD related parameters indicated that nootkatone regulated lipid metabolism and immunity via altering the gut microbiota.In conclusion,these findings revealed that nootkatone alleviated hepatic lipid homeostasis and inflammatory response in NAFLD mice,which associated with intestinal barrier integrity and the regulation of gut microbiota.This study provides new perspectives that nootkatone has efficacy on NAFLD via“gut-liver axis”,and nootkatone is expected to be developed as a functional food additive.展开更多
BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.Howeve...BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.展开更多
基金supported by grants from National Natural Science Foundation of China(82072709,81902441)Natural Science Foundation of Tianjin Municipal(23JCYBJC00850)+1 种基金China Postdoctoral Science Foundation(2022M712374)Tianjin“131”Innovative Talent Team Project(201926)。
文摘Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide.Gut microbiota and its metabolites alteration are closely related to NAFLD.Nootkatone is an edible flavorant derived from grapefruit which has a variety of biological activities.However,the precise mechanisms of nootkatone on NAFLD remains to be defined.Our results showed that nootkatone prevented body weight gain and decreased serum lipid level,hepatic lipogenesis,hepatic proinflammatory cytokines secretion in NAFLD mice.Also,nootkatone attenuated inflammatory response via inhibiting TLR4/NF-κB/NLRP3 pathway.Moreover,nootkatone restored intestinal barrier damage through increasing tight junction proteins and short chain fatty acids contents.Further 16S rRNA sequencing of colonic content suggested that nootkatone recovered the disturbed gut microbiota to improve NAFLD.Spearman correlation analysis between gut microbiota and NAFLD related parameters indicated that nootkatone regulated lipid metabolism and immunity via altering the gut microbiota.In conclusion,these findings revealed that nootkatone alleviated hepatic lipid homeostasis and inflammatory response in NAFLD mice,which associated with intestinal barrier integrity and the regulation of gut microbiota.This study provides new perspectives that nootkatone has efficacy on NAFLD via“gut-liver axis”,and nootkatone is expected to be developed as a functional food additive.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2021B1515140043,No.2022A1515140124 and No.2023A1515140115.
文摘BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor therapy.However,its specific molecular and biological mechanisms remain unclear.AIM To investigate the therapeutic effect and mechanism of modified PD in IM.METHODS This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in IM.The primary chemical components of the modified PD were identified using liquid chromatography-mass spectrometry.Body weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in IM.Effects on the TLR4/MyD88/NF-κB pathway were evaluated using western blot analysis.The intestinal microbiota was characterized using Illumina NovaSeq sequencing.RESULTS The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM mice.Mechanistically,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine IL-10.Furthermore,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and mucin-2.Finally,16S rDNA sequencing revealed that modified PD improved intestinal dysbiosis.CONCLUSION Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.
