Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease that threatens human health worldwide.The aim of this study was to detect the protective effect of a fermented Lentinus edodes extract containingα-gluc...Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease that threatens human health worldwide.The aim of this study was to detect the protective effect of a fermented Lentinus edodes extract containingα-glucan(FLA),in a concanavalin A(Con A)-induced AIH mouse model and to determine the underlying liver-protective mechanism.The results showed that compared with the model group,the level of proinflammatory cytokines in serum of FLA pretreated mice was significantly decreased,and the degree of inflammatory cell infiltration in liver,thymus and spleen was significantly reduced.Quantitative polymerase chain reaction,immunohistochemistry,and Western blotting showed that FLA pre-treatment inhibited the Con A-induced apoptosis of hepatocytes by down-regulating the expression of BAX and up-regulating the expression of BCL-2.Further research found that FLA may improve liver injury in mice by activating NRF2 signaling pathway and inhibiting TRAF6/NF-κB signaling pathway.Thus,FLA may improve liver injury in mice by shifting gut microbial composition to reduce the release of inflammatory cytokines in the serum and prevent the necrosis of hepatocytes.Up-regulation of NRF2 signaling pathway,down-regulation of TRAF6/NF-κB signaling pathway,and an increase in the relative abundance of Lactobacillus_johnsonii and Ligilactobacillus_murinus play a protective role in liver.展开更多
Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in ...Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.展开更多
This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to ex...This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury.The results show that AAM signifi cantly elevated the cell viability,ameliorated the cell morphology,reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells.Then,mice were administered with ethanol to induce acute alcoholic liver damage,and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice.As a result,AAM reduced the levels of ALT,AST,TG,and MDA,increased the levels of ADH,SOD,and CAT in liver damage mice.The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase.The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.展开更多
Trametes lactinea mycelia polysaccharides(TLMPS)have a wide range of bioactivities.The potential mechanisms of action of TLMPS against acute alcohol-induced liver injury in vivo were investigated by analyzing the phys...Trametes lactinea mycelia polysaccharides(TLMPS)have a wide range of bioactivities.The potential mechanisms of action of TLMPS against acute alcohol-induced liver injury in vivo were investigated by analyzing the physical and chemical properties of TLMPS and its protective effects on a mouse model of alcoholic liver injury.TLMPS protected the liver against alcohol-induced injury,as evidenced by the reduced alcohol-induced elevation of the liver index,serum biochemical indices,and maintenance of hepatic morphology.Potential mechanisms were analyzed using transcriptome and metabolome analyses.The transcriptome data revealed the involvement of many differentially expressed genes in chemical carcinogenesis,drug metabolism,and metabolism of xenobiotics by cytochrome P450.The metabolome analysis revealed that TLMPS significantly regulated specific metabolites in the liver,including organic acids,lipids,nucleosides,and organic oxygen compounds.KEGG enrichment analysis revealed the signifi cant involvement of different metabolites in choline metabolism,ATP-binding cassette transporters,and glycerophospholipid metabolism.Assessment of the changes in gene expression and metabolites revealed the significantly different expression of several genes encoding key enzymes and metabolites in choline metabolism pathway.The collective fi ndings confi rmed that choline metabolism plays an important role in the protective effects of TLMPS against acute alcoholic liver injury.展开更多
基金supported by the Shanghai Lithy One-Health Group Technology Co.,Ltd.,Project(114-KH210230A)。
文摘Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease that threatens human health worldwide.The aim of this study was to detect the protective effect of a fermented Lentinus edodes extract containingα-glucan(FLA),in a concanavalin A(Con A)-induced AIH mouse model and to determine the underlying liver-protective mechanism.The results showed that compared with the model group,the level of proinflammatory cytokines in serum of FLA pretreated mice was significantly decreased,and the degree of inflammatory cell infiltration in liver,thymus and spleen was significantly reduced.Quantitative polymerase chain reaction,immunohistochemistry,and Western blotting showed that FLA pre-treatment inhibited the Con A-induced apoptosis of hepatocytes by down-regulating the expression of BAX and up-regulating the expression of BCL-2.Further research found that FLA may improve liver injury in mice by activating NRF2 signaling pathway and inhibiting TRAF6/NF-κB signaling pathway.Thus,FLA may improve liver injury in mice by shifting gut microbial composition to reduce the release of inflammatory cytokines in the serum and prevent the necrosis of hepatocytes.Up-regulation of NRF2 signaling pathway,down-regulation of TRAF6/NF-κB signaling pathway,and an increase in the relative abundance of Lactobacillus_johnsonii and Ligilactobacillus_murinus play a protective role in liver.
基金supported by the National Natural Science Foundation of China(81503187)。
文摘Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.
基金This work was financially supported by the Special Fund Project for Technological Innovation of Fujian Agriculture and Forestry University(CXZX2019055G)the Science and Technology Project on Social Development of Cixi(CN2020027).
文摘This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury.The results show that AAM signifi cantly elevated the cell viability,ameliorated the cell morphology,reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells.Then,mice were administered with ethanol to induce acute alcoholic liver damage,and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice.As a result,AAM reduced the levels of ALT,AST,TG,and MDA,increased the levels of ADH,SOD,and CAT in liver damage mice.The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase.The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.
基金This work was supported by the National Key Research and Development Program of China(grant number 2019YFC1710501)the construction of a modern agricultural industrial technology system in Fujian province and an expert workstation of the modern edible mushroom industrial technology systeminvolving Pleurotus pulmonarius and Ganoderma lucidum(project number Minnong General[2019]no.144).
文摘Trametes lactinea mycelia polysaccharides(TLMPS)have a wide range of bioactivities.The potential mechanisms of action of TLMPS against acute alcohol-induced liver injury in vivo were investigated by analyzing the physical and chemical properties of TLMPS and its protective effects on a mouse model of alcoholic liver injury.TLMPS protected the liver against alcohol-induced injury,as evidenced by the reduced alcohol-induced elevation of the liver index,serum biochemical indices,and maintenance of hepatic morphology.Potential mechanisms were analyzed using transcriptome and metabolome analyses.The transcriptome data revealed the involvement of many differentially expressed genes in chemical carcinogenesis,drug metabolism,and metabolism of xenobiotics by cytochrome P450.The metabolome analysis revealed that TLMPS significantly regulated specific metabolites in the liver,including organic acids,lipids,nucleosides,and organic oxygen compounds.KEGG enrichment analysis revealed the signifi cant involvement of different metabolites in choline metabolism,ATP-binding cassette transporters,and glycerophospholipid metabolism.Assessment of the changes in gene expression and metabolites revealed the significantly different expression of several genes encoding key enzymes and metabolites in choline metabolism pathway.The collective fi ndings confi rmed that choline metabolism plays an important role in the protective effects of TLMPS against acute alcoholic liver injury.
