Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-i...Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-induced anorexia was discussed from the aspects of regulating gut microbiota,repairing intestinal barrier injury and inhibiting inflammatory pathways.Methods:A rat model of chemotherapy-induced anorexia was established using cisplatin.The study evaluated the therapeutic effects of LJZD by observing the weight,food intake,and intestinal pathology of rats.The impact of LJZD on gut microbiota and metabolites,specifically short-chain fatty acids,was investigated through gut microbiota analysis and targeted metabolomics.The anti-inflammatory and intestinal protective effects of LJZD were assessed by examining the expression of intestinal tight junction proteins associated with the inflammatory pathway.Results:LJZD alleviated cisplatin-induced inflammation and intestinal barrier disruption,as evidenced by upregulated expression of tight junction protein 1(TJ-1)and occludin,along with reduced serum levels of interleukin 6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and lipopolysaccharide.Additionally,LJZD alleviated microbiota imbalance and regulated the levels of short-chain fatty acids,especially increased the relative abundance of Coriobacteriales Incertae Sedis,Lactabacillus johnsonii F19785,Parasutterella,and reduced the Tyzzerella.In the hypothalamus,LJZD exerts suppressive effects on the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)p65 signaling pathway,leading to a downregulation in the transcriptional activity of IL-6 and IL-1β,as well as Interleukin 6 receptors(IL-6R)and Interleukin-1βreceptors(IL-1R1)mRNA expression levels.Conclusion:In summary,LJZD alleviate chemotherapy-induced anorexia by modulating the gut microbiota,repairing the intestinal mechanical barriers,and suppressing the TLR4/MyD88/NF-κB p65 signaling pathway.展开更多
Objective:To study the effects of Shenqi Tiaoshen Formula(SQTS)on the inflammatory response of MH-S cells induced by cigarette smoking extract(CSE)and its mechanism based on TLR4/NF-kB/NLRP3 pathway.Methods:MH-S cells...Objective:To study the effects of Shenqi Tiaoshen Formula(SQTS)on the inflammatory response of MH-S cells induced by cigarette smoking extract(CSE)and its mechanism based on TLR4/NF-kB/NLRP3 pathway.Methods:MH-S cells were used as subjects to evaluate cell viability by CCK-8 method.The levels of TNF-α,IL-1βand IL-6 in the supernatant were detected by ELISA.ROS were detected by DCFH-DA fluorescence probe.Western blotting was used to detect the expression of TLR4/NF-kB/NLRP3 pathway protein,and TAK-242,a TLR4 inhibitor,was used to verify the role of SQTS in the TLR4/NF-kB/NLRP3 pathway.Results:Compared with blank group,the cell survival rate of CSE group was decreased,and the contents of inflammatory cytokines TNF-α,IL-1βand IL-6 were increased(P<0.05),ROS fluorescence expression level was significantly increased(P<0.01),TLR4/NF-kB/NLRP3 pathway protein expression was significantly increased(P<0.05);Compared with CSE group,the survival rate of cells in SQTS groups was increased,and the expression levels of the above indexes were decreased(P<0.05),and TLR4/NF-kB/NLRP3 pathway protein decreased in TAK-242 groups(P<0.05).Conclusion:SQTS can reduce the inflammatory response of MH-S cells induced by CSE by inhibiting TLR4/NF-kB/NLRP3 pathway.展开更多
Objective:To study the effect of atorvastatin on atherosclerotic rabbits.Methods:A total of 60 Now Zealand male rabbits were randomly divided into the normal group,model group and atorvastatin group.The replication ra...Objective:To study the effect of atorvastatin on atherosclerotic rabbits.Methods:A total of 60 Now Zealand male rabbits were randomly divided into the normal group,model group and atorvastatin group.The replication rabbit atherosclerotic model with immune injury combined with a high fat diet feeding was used.All rabbits were sacrificed after 3 months.TLR4 and NF-κB p65 were observed by HE staining,immunohistochemistry and western blotting.Results: The expression of TLR4,NF- k B p65 were significantly increased in the model group compared widi the normal group.The expression of TI.R4 and NK- k B p65 decreased significantly in the atorvastatin group,and there was no difference compared with the normal group.Conclusions: The effect of atorvastatin on adierosclerosis may be achieved by the inhibition of the expression of TLK4 and NF-κB p65.展开更多
Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction(柴胡龙骨牡蛎汤,CHLGMLD)in rats with temporal lobe epilepsy(TLE).Methods A total of 80 Sprague-Dawley(SD)male rats were randomized into cont...Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction(柴胡龙骨牡蛎汤,CHLGMLD)in rats with temporal lobe epilepsy(TLE).Methods A total of 80 Sprague-Dawley(SD)male rats were randomized into control(CON),model(MOD),carbamazepine(CBZ,0.1 g/kg),CHLGMLD low dose(CHLGMLD-L,12.5 g/kg),and high dose(CHLGMLD-H,25 g/kg)groups,with 16 rats in each group.TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group.After the successful establishment of TLE models,all drugs were administered through gavage,and distilled water was given to rats in the CON and MOD groups for four weeks.The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-146a-3p and miR-146a-5p.The expression levels of toll-like receptor 4(TLR4),interleukin-1 receptor-associated kinase 1(IRAK1),tumor necrosis factor(TNF)receptor-associated factor 6(TRAF6),TAK1-binding protein(TAB),nuclear factor-kappa B(NF-κB),and interleukin-1 beta(IL-1β)in hippocampus were tested by immunofluorescence assay.Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately.Results CHLGMLD decreased the frequency(P<0.05)and duration(P<0.01)of seizures in rats.CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p(P<0.05),and inhibited the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β(P<0.01).The correlation analysis revealed that the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR,respectively(P<0.01).Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats,thus relieving seizures.展开更多
基金National Natural Science Foundation of China(grant numbers 82174143)the Innovative Team Project of Ordinary Universities in Guangdong Province(grant numbers 2022KCXTD016).
文摘Background:Liu-Jun-Zi decoction(LJZD),a classical nourishing formula in China,has been proven to be effective in treating chemotherapy-induced anorexia.In this study,the mechanism of LJZD in alleviating chemotherapy-induced anorexia was discussed from the aspects of regulating gut microbiota,repairing intestinal barrier injury and inhibiting inflammatory pathways.Methods:A rat model of chemotherapy-induced anorexia was established using cisplatin.The study evaluated the therapeutic effects of LJZD by observing the weight,food intake,and intestinal pathology of rats.The impact of LJZD on gut microbiota and metabolites,specifically short-chain fatty acids,was investigated through gut microbiota analysis and targeted metabolomics.The anti-inflammatory and intestinal protective effects of LJZD were assessed by examining the expression of intestinal tight junction proteins associated with the inflammatory pathway.Results:LJZD alleviated cisplatin-induced inflammation and intestinal barrier disruption,as evidenced by upregulated expression of tight junction protein 1(TJ-1)and occludin,along with reduced serum levels of interleukin 6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and lipopolysaccharide.Additionally,LJZD alleviated microbiota imbalance and regulated the levels of short-chain fatty acids,especially increased the relative abundance of Coriobacteriales Incertae Sedis,Lactabacillus johnsonii F19785,Parasutterella,and reduced the Tyzzerella.In the hypothalamus,LJZD exerts suppressive effects on the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)p65 signaling pathway,leading to a downregulation in the transcriptional activity of IL-6 and IL-1β,as well as Interleukin 6 receptors(IL-6R)and Interleukin-1βreceptors(IL-1R1)mRNA expression levels.Conclusion:In summary,LJZD alleviate chemotherapy-induced anorexia by modulating the gut microbiota,repairing the intestinal mechanical barriers,and suppressing the TLR4/MyD88/NF-κB p65 signaling pathway.
基金Regional Innovation Development Joint Fund of National Natural Science Foundation of China(No.U20A20398)Clinical Medical Research Transformation Project of Anhui Provincial Science and Technology Department(No.202204295107020045)。
文摘Objective:To study the effects of Shenqi Tiaoshen Formula(SQTS)on the inflammatory response of MH-S cells induced by cigarette smoking extract(CSE)and its mechanism based on TLR4/NF-kB/NLRP3 pathway.Methods:MH-S cells were used as subjects to evaluate cell viability by CCK-8 method.The levels of TNF-α,IL-1βand IL-6 in the supernatant were detected by ELISA.ROS were detected by DCFH-DA fluorescence probe.Western blotting was used to detect the expression of TLR4/NF-kB/NLRP3 pathway protein,and TAK-242,a TLR4 inhibitor,was used to verify the role of SQTS in the TLR4/NF-kB/NLRP3 pathway.Results:Compared with blank group,the cell survival rate of CSE group was decreased,and the contents of inflammatory cytokines TNF-α,IL-1βand IL-6 were increased(P<0.05),ROS fluorescence expression level was significantly increased(P<0.01),TLR4/NF-kB/NLRP3 pathway protein expression was significantly increased(P<0.05);Compared with CSE group,the survival rate of cells in SQTS groups was increased,and the expression levels of the above indexes were decreased(P<0.05),and TLR4/NF-kB/NLRP3 pathway protein decreased in TAK-242 groups(P<0.05).Conclusion:SQTS can reduce the inflammatory response of MH-S cells induced by CSE by inhibiting TLR4/NF-kB/NLRP3 pathway.
基金supportcd by the National Natural Science Fnundation of China(No:81202731)Shanghai Monicipal Health Bureau Fund(No.20114047)
文摘Objective:To study the effect of atorvastatin on atherosclerotic rabbits.Methods:A total of 60 Now Zealand male rabbits were randomly divided into the normal group,model group and atorvastatin group.The replication rabbit atherosclerotic model with immune injury combined with a high fat diet feeding was used.All rabbits were sacrificed after 3 months.TLR4 and NF-κB p65 were observed by HE staining,immunohistochemistry and western blotting.Results: The expression of TLR4,NF- k B p65 were significantly increased in the model group compared widi the normal group.The expression of TI.R4 and NK- k B p65 decreased significantly in the atorvastatin group,and there was no difference compared with the normal group.Conclusions: The effect of atorvastatin on adierosclerosis may be achieved by the inhibition of the expression of TLK4 and NF-κB p65.
基金National Natural Science Foundation of China(81874429)Natural Science Foundation of Hunan Province(2020JJ5294)+3 种基金Traditional Chinese Medicine Science&Research Project of Hunan Province(202145)Excellent Youth Program of Hunan Education Department(21B0081)Hunan Provincial Administration of Traditional Chinese Medicine(D2022027)Changsha Natural Science Foundation of China(KQ2202255).
文摘Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction(柴胡龙骨牡蛎汤,CHLGMLD)in rats with temporal lobe epilepsy(TLE).Methods A total of 80 Sprague-Dawley(SD)male rats were randomized into control(CON),model(MOD),carbamazepine(CBZ,0.1 g/kg),CHLGMLD low dose(CHLGMLD-L,12.5 g/kg),and high dose(CHLGMLD-H,25 g/kg)groups,with 16 rats in each group.TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group.After the successful establishment of TLE models,all drugs were administered through gavage,and distilled water was given to rats in the CON and MOD groups for four weeks.The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-146a-3p and miR-146a-5p.The expression levels of toll-like receptor 4(TLR4),interleukin-1 receptor-associated kinase 1(IRAK1),tumor necrosis factor(TNF)receptor-associated factor 6(TRAF6),TAK1-binding protein(TAB),nuclear factor-kappa B(NF-κB),and interleukin-1 beta(IL-1β)in hippocampus were tested by immunofluorescence assay.Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately.Results CHLGMLD decreased the frequency(P<0.05)and duration(P<0.01)of seizures in rats.CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p(P<0.05),and inhibited the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β(P<0.01).The correlation analysis revealed that the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR,respectively(P<0.01).Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats,thus relieving seizures.
