This paper reviews the related formulas of Sugemule,introduces the advances in research of clinical application of these formulas in treating Heyi type insomnia,cardiac diseases,and renal diseases.Besides,it summarize...This paper reviews the related formulas of Sugemule,introduces the advances in research of clinical application of these formulas in treating Heyi type insomnia,cardiac diseases,and renal diseases.Besides,it summarizes pharmacological research advances regarding these formulas,including their anti-insomnia effects,cardioprotective properties,and ovarian function preservation capabilities.This study is expected to provide a reference and insight for in-depth and systematic research on classical Mongolian medicinal formulas.展开更多
Background:This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats,particularly induced by diethylnitrosamine(DEN).The study focused on analyzing liver str...Background:This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats,particularly induced by diethylnitrosamine(DEN).The study focused on analyzing liver structure,cell apoptosis,and the modulation of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway,employing a combination of network pharmacology and experimental approaches.Methods:A DEN-induced rat model of liver cirrhosis was established to assess the formula’s effectiveness.Parameters such as overall health,liver morphology,and survival were monitored.Network pharmacology was employed to decipher the active compounds and key targets of the formula in addressing liver cirrhosis.Predictions made via network pharmacology were substantiated through experimental validation in the animal model.Results:Administration of the Yigan Xiaozheng formula led to noticeable improvements in clinical symptoms of liver cirrhosis in rats,marked by enhanced body weight,lessened liver pathology,and higher survival rates.Network pharmacological analysis unveiled intricate interactions between active ingredients of the formula and cirrhosis-related targets.Protein-protein interaction(PPI)networks pinpointed crucial proteins and regulatory modules.Enrichment analysis underscored a significant involvement of the JAK2/STAT3 signaling pathway.On a molecular scale,the formula was observed to reduce the expression of BCL-2 associated X protein(Bax)and cytochrome C(Cyt-C),diminish the Bax/B-cell lymphoma 2(Bcl-2)ratio,and impede JAK2/STAT3 pathway activation,thereby curtailing liver fibrosis and cellular apoptosis.Conclusion:The study demonstrates the Yigan Xiaozheng formula’s capacity to ameliorate liver cirrhosis in a DEN-induced model,primarily through its active ingredients’interactions with cirrhosis targets and modulation of the JAK2/STAT3 pathway.These findings endorse the potential of this traditional Chinese medicinal formula as a viable treatment option for liver cirrhosis.展开更多
Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)sig...Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.展开更多
The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as crucial.The Yanggan Jiangmei Formula(YGJMF)has shown promise in amel...The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as crucial.The Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely unexplored.This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings.To simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were utilized.The severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels.The results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid accumulation.Additionally,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum.Furthermore,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models.The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.展开更多
Objective:To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula(HTQS for-mula),for the health management and treatment of non-alcoholic fatty liver disease(NAFLD).Methods:A rat model of NAFLD was ...Objective:To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula(HTQS for-mula),for the health management and treatment of non-alcoholic fatty liver disease(NAFLD).Methods:A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula.In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology.The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot.Finally,16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids(SCFAs)and bile acids to determine the impact of the HTQS formula on gut microbiota.Results:The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol(TC),triglycerides,blood glucose,and insulin resistance(IR)without causing liver or kidney injury.We detected 28 components using UPLC‒MS/MS and identified 439 shared targets be-tween NAFLD and the HTQS formula.Primarily,we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis.We validated that the HTQS formula inhibited liver stea-tosis and inflammation by increasing the phosphorylation levels of PI3K,AKT,P27,GSK3b in the PI3K/Akt signaling pathway.16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group,which was positively correlated with IR and taurodeoxycholic acid.In addition,Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids,which could be essential to the therapeutic effect of the HTQS formula against NAFLD.Conclusions:The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury.Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.展开更多
Objective:Ovarian cancer(OC)is the most lethal gynecological malignancy.Frequent peritoneal dissemination is the main cause of low survival rate.Guizhi-Fuling formula(GZFL)is a classical traditional Chinese herbal for...Objective:Ovarian cancer(OC)is the most lethal gynecological malignancy.Frequent peritoneal dissemination is the main cause of low survival rate.Guizhi-Fuling formula(GZFL)is a classical traditional Chinese herbal formula,and has been clinically used for treating ovarian cancer with good outcome.However,its therapeutic mechanism for treating OC has not been clearly elucidated.Methods:Network pharmacology analysis was used to predict potential molecular mechanisms of GZFL in treating OC.In vitro and in vivo analysis,including STAT3 KO/WT cells proliferation assay,scratch assay and antitumor efficacy study were performed to assess the biological activity of GZFL on targeting STAT3 in OC cells.Results:We generated a“GZFL target-OC-STAT3”gene interaction network,and predicted that GZFL is tightly associated with IL6/JAK/STAT3 signal pathway and cancer metastasis.Our preliminary data showed that GZFL inhibited OC cell proliferation in a STAT3 dependent manner.It suppressed cell migration and downregulated p-STAT3 expression.In a tumor bearing mouse model,GZFL displayed a safety profile.Conclusion:GZFL inhibits OC progression by targeting STAT3 signaling network.Our newly proposed pharmacological mechanisms of Guizhi-Fuling formula will provide a new insight for its clinical use in treating OC.展开更多
As concepts closely related to microwave absorption properties,impedance matching and phase matching were rarely combined with material parameters to regulate properties and explore related mechanisms.In this work,red...As concepts closely related to microwave absorption properties,impedance matching and phase matching were rarely combined with material parameters to regulate properties and explore related mechanisms.In this work,reduction–diffusion method was innovatively applied to synthesize rare earth alloy Y_(2)Fe_(17).In order to regulate the electromagnetic parameters of absorbers,the Y_(2)Fe_(17)N_(3-δ)particles were coated with silica(Y_(2)Fe_(17)N_(3-δ)@SiO_(2))and absorbers with different volume fractions were prepared.The relationship between impedance matching,matching thickness,and the strongest reflection loss peak(RLmin)was presented obviously.Compared to the microwave absorption properties of Y_(2)Fe_(17)N_(3-δ)/PU absorber,Y_(2)Fe_(17)N_(3-δ)@SiO_(2)/PU absorbers are more conducive to the realization of microwave absorption material standards which are thin thickness,light weight,strong absorbing intensity,and broad bandwidth.Based on microwave frequency bands,the microwave absorption properties of the absorbers were analyzed and the related parameters were listed.As an important parameter related to perfect matching,reflection factor(√ε_(r)/μ_(r))was discussed combined with microwave amplitude attenuation.According to the origin and mathematical model of bandwidth,the formula of EAB(RL<-10 dB)was derived and simplified.The calculated bandwidths agreed well with experimental results.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 explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT...Objective:To explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT3 signaling pathway.Methods:Fifty SD rats were randomly divided into five groups,blank group,model group,choling tablets(0.5 g/kg),and low and high concentration groups(2.4 g/kg and 4.8 g/kg)of Dahuang Lingxian Formula,ten rats in each group.Except for the blank group,the rats in each group were injected with 1.25 mg/kg LPS at the common bile duct at one time to construct an animal model of intrahepatic bile duct infection.After gavage on day 8,liver tissues were taken from rats at the hepatic hilum,and the histopathological changes of the hepatic hilum and biliary tree were observed by HE staining.The expression levels of serum glutamic alanine transaminase(ALT),glutamic oxalacetic transaminase(AST),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by biochemical method.The expression levels of interleukin 6(IL-6),Janus protein tyrosine kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3)in rat serum were measured by enzyme-linked immunosorbent assay(ELISA).Protein immunoblotting(WB)and real-time fluorescence quantitative PCR(RT-qPCR)were used to detect the expression levels of IL-6,JAK2,STAT3 protein and mRNA in biliary tree tissues.Results:①Compared with the blank group,the structures such as interlobular bile ducts in the hepatic sinusoids and portal duct area of the model rats were destroyed,and inflammatory cells infiltrated around them.The expression of ALT,AST,MDA,IL-6,JAK2 and STAT3 in the serum increased significantly,the expression level of SOD decreased,and the expression levels of IL-6,JAK2 and STAT3 proteins and mRNA increased.②Compared with the model group,the degree of liver pathological damage in rats in the Chiling Ning tablet group and the low and high concentration groups of Dahuang Lingxian Formula were improved,which could significantly reduce the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and up-regulate SOD in serum,and down-regulate the expression of IL-6,JAK2,STAT3 protein and mRNA,with the best effect in the high concentration group of Dahuang Lingxian Formula.③Compared with the choling tablet group,the rats in the low and high concentration groups of Dahuang Lingxian Formula tended to normalize the degree of liver pathological damage,without obvious inflammatory cell infiltration,and the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and the expression levels of IL-6,JAK2,STAT3 protein and mRNA in serum were reduced,and the expression levels of SOD were increased,with the best effect of Dahuang Lingxian Formula The treatment effect was best in the high concentration group.Conclusion:The mechanism may be related to the down-regulation of IL-6/JAK/STAT3 signaling pathway activation,and the best therapeutic effect was achieved by the high concentration group of Dahuang Lingxian Formula.展开更多
[Objectives]To observe the effects of Cigu Xiaozhi Formula on miR-378a-3p expression and Hh signaling pathway in TGF-β1 induced and activated LX2 cells.[Methods]Cells were divided into control group,induction group,d...[Objectives]To observe the effects of Cigu Xiaozhi Formula on miR-378a-3p expression and Hh signaling pathway in TGF-β1 induced and activated LX2 cells.[Methods]Cells were divided into control group,induction group,drug-containing serum group,miR-378a-3p inhibitor group,and miR inhibitor NC group.CCK-8 method was used to detect the cell viability of each group,and flow cytometry was used to detect the apoptosis rate of each group.RT-qPCR was used to detect the expression of miR-378a-3p in each group s cells,and RT-qPCR and Western blot were used to detect mRNA and protein expression of Shh,Gli1,Gli2,Col-I,andα-SMA in each group s cells.[Results]Compared with the control group,the cell viability and expression of Shh,Gli1,Gli2,Col-I,andα-SMA mRNA and protein in induction group increased(P<0.01),while the expression of miR-378a-3p decreased(P<0.01).Compared with the induction group,the cell viability and expression of Shh,Gli1,Gli2,Col-I,α-SMA mRNA andα-SMA and Gli2 protein decreased in drug-containing serum group(P<0.05),while cell apoptosis rate and miR-378a-3p expression increased(P<0.01).In miR-378a-3p inhibitor group,cell viability and the expression of Shh,Gli1,Gli2,Col-I,α-SMA mRNA and Gli1,Gli2,α-SMA protein increased(P<0.05,P<0.01),while the apoptosis rate and miR-378a-3p expression decreased(P<0.05,P<0.01).[Conclusions]Cigu Xiaozhi Formula containing serum can upregulate miR-378a-3p expression and downregulate the expression of Gli2 andα-SMA in TGF-β1 induced LX2 cells,thereby inhibiting the activation of LX2 cells and exerting the effects of anti liver fibrosis.展开更多
基金Supported by Laboratory Open Fund Project of Inner Mongolia Medical University in 2024(2024ZN20)Key Laboratory of Mongolian Medicine Open Fund Project of Inner Mongolia Autonomous Region(GX20240003)+2 种基金Inner Mongolia Medicine Collaborative Innovation Center Achievement Transformation and Cultivation Project(MYYXTPY202402)Project of Construction of Key Laboratory of Mongolian Medicine in Universities of Inner Mongolia Autonomous Region(RZ2400000451)Project of Construction of Key Laboratory of Mongolian Medicine Research Platform in Inner Mongolia Autonomous Region(DC2400000724).
文摘This paper reviews the related formulas of Sugemule,introduces the advances in research of clinical application of these formulas in treating Heyi type insomnia,cardiac diseases,and renal diseases.Besides,it summarizes pharmacological research advances regarding these formulas,including their anti-insomnia effects,cardioprotective properties,and ovarian function preservation capabilities.This study is expected to provide a reference and insight for in-depth and systematic research on classical Mongolian medicinal formulas.
基金supported by National Natural Science Foundation of China Grant Program(No.81603555).
文摘Background:This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats,particularly induced by diethylnitrosamine(DEN).The study focused on analyzing liver structure,cell apoptosis,and the modulation of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway,employing a combination of network pharmacology and experimental approaches.Methods:A DEN-induced rat model of liver cirrhosis was established to assess the formula’s effectiveness.Parameters such as overall health,liver morphology,and survival were monitored.Network pharmacology was employed to decipher the active compounds and key targets of the formula in addressing liver cirrhosis.Predictions made via network pharmacology were substantiated through experimental validation in the animal model.Results:Administration of the Yigan Xiaozheng formula led to noticeable improvements in clinical symptoms of liver cirrhosis in rats,marked by enhanced body weight,lessened liver pathology,and higher survival rates.Network pharmacological analysis unveiled intricate interactions between active ingredients of the formula and cirrhosis-related targets.Protein-protein interaction(PPI)networks pinpointed crucial proteins and regulatory modules.Enrichment analysis underscored a significant involvement of the JAK2/STAT3 signaling pathway.On a molecular scale,the formula was observed to reduce the expression of BCL-2 associated X protein(Bax)and cytochrome C(Cyt-C),diminish the Bax/B-cell lymphoma 2(Bcl-2)ratio,and impede JAK2/STAT3 pathway activation,thereby curtailing liver fibrosis and cellular apoptosis.Conclusion:The study demonstrates the Yigan Xiaozheng formula’s capacity to ameliorate liver cirrhosis in a DEN-induced model,primarily through its active ingredients’interactions with cirrhosis targets and modulation of the JAK2/STAT3 pathway.These findings endorse the potential of this traditional Chinese medicinal formula as a viable treatment option for liver cirrhosis.
基金National Natural Science Foundation of China(U21A20411)Innovative Research Group Program of Hunan Provincial Natural Science Foundation (2024JJ1007)Hunan Provincial Natural Science Foundation(2023JJ30473)。
文摘Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
基金supported by the National Natural Science Foundation of China(No.8200151236)the Postgraduate Research Practice Innovation Program of Jiangsu Province(No.KYCX22_1903)the Outstanding Clinical Talents of Traditional Chinese Medicine in Jiangsu Province(No.18,Jiangsu Science and Education of Traditional Chinese Medicine[2017]).
文摘The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as crucial.The Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely unexplored.This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings.To simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were utilized.The severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels.The results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid accumulation.Additionally,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum.Furthermore,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models.The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.
基金supported by the General Program of National Natural Science Foundation of China(82374308)National Key Research and Development Program(NKRDP)(2022YFC2010104)Henan Province Special Projects of Traditional Chinese Medicine Science Research(2024ZY2067),and National Talent Precision Cultivation Plan of the Beijing University of Chinese Medicine.
文摘Objective:To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula(HTQS for-mula),for the health management and treatment of non-alcoholic fatty liver disease(NAFLD).Methods:A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula.In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology.The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot.Finally,16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids(SCFAs)and bile acids to determine the impact of the HTQS formula on gut microbiota.Results:The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol(TC),triglycerides,blood glucose,and insulin resistance(IR)without causing liver or kidney injury.We detected 28 components using UPLC‒MS/MS and identified 439 shared targets be-tween NAFLD and the HTQS formula.Primarily,we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis.We validated that the HTQS formula inhibited liver stea-tosis and inflammation by increasing the phosphorylation levels of PI3K,AKT,P27,GSK3b in the PI3K/Akt signaling pathway.16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group,which was positively correlated with IR and taurodeoxycholic acid.In addition,Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids,which could be essential to the therapeutic effect of the HTQS formula against NAFLD.Conclusions:The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury.Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.
文摘Objective:Ovarian cancer(OC)is the most lethal gynecological malignancy.Frequent peritoneal dissemination is the main cause of low survival rate.Guizhi-Fuling formula(GZFL)is a classical traditional Chinese herbal formula,and has been clinically used for treating ovarian cancer with good outcome.However,its therapeutic mechanism for treating OC has not been clearly elucidated.Methods:Network pharmacology analysis was used to predict potential molecular mechanisms of GZFL in treating OC.In vitro and in vivo analysis,including STAT3 KO/WT cells proliferation assay,scratch assay and antitumor efficacy study were performed to assess the biological activity of GZFL on targeting STAT3 in OC cells.Results:We generated a“GZFL target-OC-STAT3”gene interaction network,and predicted that GZFL is tightly associated with IL6/JAK/STAT3 signal pathway and cancer metastasis.Our preliminary data showed that GZFL inhibited OC cell proliferation in a STAT3 dependent manner.It suppressed cell migration and downregulated p-STAT3 expression.In a tumor bearing mouse model,GZFL displayed a safety profile.Conclusion:GZFL inhibits OC progression by targeting STAT3 signaling network.Our newly proposed pharmacological mechanisms of Guizhi-Fuling formula will provide a new insight for its clinical use in treating OC.
基金Project supported by the National Key Research and Development Program of China(Grant No.2021YFB3501300)the National Natural Science Foundation of China(Grant No.51731001)the Fund from the State Key Laboratory of Baiyunobo Rare Earth Resource Researches and Comprehensive Utilization’s Key Research and Development Projects。
文摘As concepts closely related to microwave absorption properties,impedance matching and phase matching were rarely combined with material parameters to regulate properties and explore related mechanisms.In this work,reduction–diffusion method was innovatively applied to synthesize rare earth alloy Y_(2)Fe_(17).In order to regulate the electromagnetic parameters of absorbers,the Y_(2)Fe_(17)N_(3-δ)particles were coated with silica(Y_(2)Fe_(17)N_(3-δ)@SiO_(2))and absorbers with different volume fractions were prepared.The relationship between impedance matching,matching thickness,and the strongest reflection loss peak(RLmin)was presented obviously.Compared to the microwave absorption properties of Y_(2)Fe_(17)N_(3-δ)/PU absorber,Y_(2)Fe_(17)N_(3-δ)@SiO_(2)/PU absorbers are more conducive to the realization of microwave absorption material standards which are thin thickness,light weight,strong absorbing intensity,and broad bandwidth.Based on microwave frequency bands,the microwave absorption properties of the absorbers were analyzed and the related parameters were listed.As an important parameter related to perfect matching,reflection factor(√ε_(r)/μ_(r))was discussed combined with microwave amplitude attenuation.According to the origin and mathematical model of bandwidth,the formula of EAB(RL<-10 dB)was derived and simplified.The calculated bandwidths agreed well with experimental results.
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Guangxi Natural Science Foundation(No.2020GXNSFAA238012)Research on Traditional Chinese Medicine Prevention and Treatment of Liver and Bile Related Diseases in the 2021"Qihuang Project"High Level Talent Team Cultivation Project(No.2021006)+1 种基金2020 Guangxi University of Traditional Chinese Medicine First Affiliated Hospital Hospital Hospital Level Doctoral Initiation Fund Project(No.2020BS004)2020 Guangxi University of Traditional Chinese Medicine Introduction Doctoral Research Initiation Fund Project(No.2020BS030)。
文摘Objective:To explore the mechanism of action of Dahuang Lingxian Formula in alleviating the inflammatory response of bile duct cells in LPS-induced intrahepatic bile duct inflammation model rats based on IL-6/JAK/STAT3 signaling pathway.Methods:Fifty SD rats were randomly divided into five groups,blank group,model group,choling tablets(0.5 g/kg),and low and high concentration groups(2.4 g/kg and 4.8 g/kg)of Dahuang Lingxian Formula,ten rats in each group.Except for the blank group,the rats in each group were injected with 1.25 mg/kg LPS at the common bile duct at one time to construct an animal model of intrahepatic bile duct infection.After gavage on day 8,liver tissues were taken from rats at the hepatic hilum,and the histopathological changes of the hepatic hilum and biliary tree were observed by HE staining.The expression levels of serum glutamic alanine transaminase(ALT),glutamic oxalacetic transaminase(AST),malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by biochemical method.The expression levels of interleukin 6(IL-6),Janus protein tyrosine kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3)in rat serum were measured by enzyme-linked immunosorbent assay(ELISA).Protein immunoblotting(WB)and real-time fluorescence quantitative PCR(RT-qPCR)were used to detect the expression levels of IL-6,JAK2,STAT3 protein and mRNA in biliary tree tissues.Results:①Compared with the blank group,the structures such as interlobular bile ducts in the hepatic sinusoids and portal duct area of the model rats were destroyed,and inflammatory cells infiltrated around them.The expression of ALT,AST,MDA,IL-6,JAK2 and STAT3 in the serum increased significantly,the expression level of SOD decreased,and the expression levels of IL-6,JAK2 and STAT3 proteins and mRNA increased.②Compared with the model group,the degree of liver pathological damage in rats in the Chiling Ning tablet group and the low and high concentration groups of Dahuang Lingxian Formula were improved,which could significantly reduce the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and up-regulate SOD in serum,and down-regulate the expression of IL-6,JAK2,STAT3 protein and mRNA,with the best effect in the high concentration group of Dahuang Lingxian Formula.③Compared with the choling tablet group,the rats in the low and high concentration groups of Dahuang Lingxian Formula tended to normalize the degree of liver pathological damage,without obvious inflammatory cell infiltration,and the expression levels of ALT,AST,MDA,IL-6,JAK2,STAT3 and the expression levels of IL-6,JAK2,STAT3 protein and mRNA in serum were reduced,and the expression levels of SOD were increased,with the best effect of Dahuang Lingxian Formula The treatment effect was best in the high concentration group.Conclusion:The mechanism may be related to the down-regulation of IL-6/JAK/STAT3 signaling pathway activation,and the best therapeutic effect was achieved by the high concentration group of Dahuang Lingxian Formula.
基金Supported by Regional Fund Project of National Natural Science Foundation of China(81860821)Gansu Province Higher Education Innovation Ability Enhancement Project in 2019(2019B-104)Innovation and Entrepreneurship Fund for Graduate Students of Gansu University of Chinese Medicine(2022CX64).
文摘[Objectives]To observe the effects of Cigu Xiaozhi Formula on miR-378a-3p expression and Hh signaling pathway in TGF-β1 induced and activated LX2 cells.[Methods]Cells were divided into control group,induction group,drug-containing serum group,miR-378a-3p inhibitor group,and miR inhibitor NC group.CCK-8 method was used to detect the cell viability of each group,and flow cytometry was used to detect the apoptosis rate of each group.RT-qPCR was used to detect the expression of miR-378a-3p in each group s cells,and RT-qPCR and Western blot were used to detect mRNA and protein expression of Shh,Gli1,Gli2,Col-I,andα-SMA in each group s cells.[Results]Compared with the control group,the cell viability and expression of Shh,Gli1,Gli2,Col-I,andα-SMA mRNA and protein in induction group increased(P<0.01),while the expression of miR-378a-3p decreased(P<0.01).Compared with the induction group,the cell viability and expression of Shh,Gli1,Gli2,Col-I,α-SMA mRNA andα-SMA and Gli2 protein decreased in drug-containing serum group(P<0.05),while cell apoptosis rate and miR-378a-3p expression increased(P<0.01).In miR-378a-3p inhibitor group,cell viability and the expression of Shh,Gli1,Gli2,Col-I,α-SMA mRNA and Gli1,Gli2,α-SMA protein increased(P<0.05,P<0.01),while the apoptosis rate and miR-378a-3p expression decreased(P<0.05,P<0.01).[Conclusions]Cigu Xiaozhi Formula containing serum can upregulate miR-378a-3p expression and downregulate the expression of Gli2 andα-SMA in TGF-β1 induced LX2 cells,thereby inhibiting the activation of LX2 cells and exerting the effects of anti liver fibrosis.
