Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approve...Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.展开更多
<strong>Objective:</strong> To investigate the potential mechanism of Drynariae Rhizoma-Epimedii Folium in the treatment of osteoarthritis (OA) based on network pharmacology. <strong>Methods:</str...<strong>Objective:</strong> To investigate the potential mechanism of Drynariae Rhizoma-Epimedii Folium in the treatment of osteoarthritis (OA) based on network pharmacology. <strong>Methods:</strong> The potential active constituents and targets of Drynariae Rhizoma-Epimedii Folium were screened through the traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP). Genecards database is used to find relevant targets of OA. The targets of “Drynariae Rhizoma-Epimedii Folium” were mapped to the targets of OA, and used Cytoscape software to build a “drug-ingredient-target-di- sease” regulatory network and protein protein interaction (PPI) network. R software was used to analyze the Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment of traditional Chinese medicine-disease targets. <strong>Results:</strong> Thirty-four effective ingredients and 130 traditional Chinese medicine-disease targets were screened out for the treatment of OA. The GO functions of traditional Chinese medicine-disease targets mainly included cytokine activity, cytokine receptor binding, nuclear receptor activity, transcription factor activity, proximal promoter DNA-binding transcription activator activity, DNA-binding transcription activator activity, phosphatase binding and so on. KEGG pathways involved in traditional Chinese medicine-disease targets mainly included TLR4 signaling pathway, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K/AKT signaling pathway, apoptotic signaling pathway and so on. <strong>Conclusion:</strong> Network pharmacology may predict the multiple targets and multiple signaling pathways in Drynariae Rhizoma-Epimedii Folium treatment for OA, providing new ideas for future research.展开更多
Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induc...Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.展开更多
OBJECTIVE:To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo(Herba Epimedii Brevicornus) and its extract in treating chronic obstructive pu...OBJECTIVE:To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo(Herba Epimedii Brevicornus) and its extract in treating chronic obstructive pulmonary disease(COPD).METHODS:First,Meta-analysis was carried out.The Chinese and English literature of Yinyanghuo(Herba Epimedii Brevicornus) in treating COPD was searched using the systematic strategy of combining subject words with free words.The included studies were evaluated by the SYRCLE risk bias assessment tool,after which the review manager software was used to combine the effect quantities for statistical analysis.Then,based on bioinformatics technology,the active ingredients and their targets of Yinyanghuo(Herba Epimedii Brevicornus) were screened,and the intersection genes were obtained by mapping and comparing with the targets of COPD.The "medicinal materials-compounds-targets model" was constructed,and the key pathways were annotated.Finally,the core target was docked with important compounds.RESULTS:A total of 8 studies were included in the Metaanalysis.The results showed that the Yinyanghuo(Herba Epimedii Brevicornus) group could significantly downregulate pro-inflammatory factors such as tumor necrosis factor-α(TNF-α) and interleukin(IL)-8 and increase the expression of anti-inflammatory factors and antioxidant factors such as IL-10 and phospho-protein kinase B(pAKT) in the COPD model(all P < 0.05).A total of 23 active components and 102 corresponding target genes of Yinyanghuo(Herba Epimedii Brevicornus) were obtained by bioinformatics technology,among which 17 compounds and 63 targets were closely related to COPD.The results of enrichment analysis mainly included TNF signaling pathway,phosphoinositide 3-kinase(PI3K)/Akt signaling pathway,cancer signaling pathway,and other inflammatory reactions,oxidative stress,and tumorrelated pathways.The molecular docking results showed that the binding energy fractions of the top five components of 24-epicampesterol with 10 core targets such as IL-6 were all less than ﹣5.0 kcal/mol,suggesting good binding ability.CONCLUSIONS:Meta-analysis and bioinformatics results indicated that the therapeutic effect of Yinyanghuo(Herba Epimedii Brevicornus) and its components on COPD might be related to antagonizing inflammation and oxidative stress.The above findings provide a preliminary basis for the development of Yinyanghuo(Herba Epimedii Brevicornus) as a natural drug for preventing and treating COPD.展开更多
Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zh...Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.展开更多
Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely u...Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly understood.Increasing evidence has indicated that most cases of IDILI are immune mediated.Here,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation.ICSⅡexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome activation.Importantly,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.展开更多
OBJECTIVE:To evaluate the effects of a combination of Yinyanghuo(Herba Epimedii Brevicornus)(HEB)and Cheqianzi(Semen Plantaginis)(SP)on erectile dysfunction caused by essential hypertension in spontaneously hypertensi...OBJECTIVE:To evaluate the effects of a combination of Yinyanghuo(Herba Epimedii Brevicornus)(HEB)and Cheqianzi(Semen Plantaginis)(SP)on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats(SHRs),and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor(ACE2/Ang[1-7]/Mas receptor)axis in this process.METHODS:A total of 24 SHRs were randomly assigned to three groups:SHR-control,low-dose(12.5 g/kg)and high-dose(25 g/kg)HEB+SP(HEBSP).Eight Wistar-Kyoto rats were used as normal controls.HEBSP was administered by oral gavage for 28 d.Erectile function was measured once a week using the Heaton test.After 4 weeks of treatment,the corpus cavernosum was harvested from each rat to measure nitric oxide(NO),nitric oxide synthase(e NOS)and Ang(1-7)levels,as well as ACE2,Mas receptor and neuronal nitric oxide synthase(n NOS)protein expression.RESULTS:After 4 weeks of treatment,HEBSP significantly increased erectile function in the treated group compared with SHR-control group(P<0.01).Additionally,HEBSP treatment significantly increased cavernosal levels of Ang(1-7),e NOS and NO.Moreover,HEBSP significantly elevated the expression levels of ACE2,Mas receptor and n NOS.These beneficial effects were elevated in the high-dose HEBSP group.CONCLUSION:HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang(1-7)/Mas receptor axis,e NOS and n NOS pathways.展开更多
OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism...OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism in a rat model of PCOS.METHODS:A network pharmacology approach involving a characteristic drug assessment,active compound and target prediction,PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS:Six networks were constructed,an active compound-target network for the ECD(C-T network),a drug-target network(D-T network),a related genes network,a targets interaction network,a key genes interaction network,and a gene-pathway network.A total of 41 compounds and 261 targets were identified for the ECD,232 PCOS-related genes,31 cogenes,and 14 pathways.These pathways may be involved in the efficacy of ECD on PCOS.The proteins most involved in the signal pathways for all targets were AKT1,IL6,INSR,ESR,and GSK3B.The AKT1 target was selected for experimental verification.Based on the Western blot and real-time PCR results,the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS:Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81873196)Sino-German Center for Research Promotion(Project No.:GZ1505)Chinese Scholarship Council,and Science and Technology Planning Projects of Jiaxing City(Project No.:2022AY10014).
文摘Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.
文摘<strong>Objective:</strong> To investigate the potential mechanism of Drynariae Rhizoma-Epimedii Folium in the treatment of osteoarthritis (OA) based on network pharmacology. <strong>Methods:</strong> The potential active constituents and targets of Drynariae Rhizoma-Epimedii Folium were screened through the traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP). Genecards database is used to find relevant targets of OA. The targets of “Drynariae Rhizoma-Epimedii Folium” were mapped to the targets of OA, and used Cytoscape software to build a “drug-ingredient-target-di- sease” regulatory network and protein protein interaction (PPI) network. R software was used to analyze the Gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment of traditional Chinese medicine-disease targets. <strong>Results:</strong> Thirty-four effective ingredients and 130 traditional Chinese medicine-disease targets were screened out for the treatment of OA. The GO functions of traditional Chinese medicine-disease targets mainly included cytokine activity, cytokine receptor binding, nuclear receptor activity, transcription factor activity, proximal promoter DNA-binding transcription activator activity, DNA-binding transcription activator activity, phosphatase binding and so on. KEGG pathways involved in traditional Chinese medicine-disease targets mainly included TLR4 signaling pathway, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K/AKT signaling pathway, apoptotic signaling pathway and so on. <strong>Conclusion:</strong> Network pharmacology may predict the multiple targets and multiple signaling pathways in Drynariae Rhizoma-Epimedii Folium treatment for OA, providing new ideas for future research.
文摘Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.
基金Supported by National Natural Science Foundation of China:Construction of"Three Dimensional Model of Shenqi deficiency syndrome COPD-Bushenyigi Formulae-biomarker spectrum"of Traditional Chinese Medicine (No. 81760901)Tianshan Innovation Team Plan of Xinjiang:Traditional Chinese Medicine Research Team on Prevention and Treatment of Chronic Obstructive Pulmonary Disease (No. 2017D14013)。
文摘OBJECTIVE:To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo(Herba Epimedii Brevicornus) and its extract in treating chronic obstructive pulmonary disease(COPD).METHODS:First,Meta-analysis was carried out.The Chinese and English literature of Yinyanghuo(Herba Epimedii Brevicornus) in treating COPD was searched using the systematic strategy of combining subject words with free words.The included studies were evaluated by the SYRCLE risk bias assessment tool,after which the review manager software was used to combine the effect quantities for statistical analysis.Then,based on bioinformatics technology,the active ingredients and their targets of Yinyanghuo(Herba Epimedii Brevicornus) were screened,and the intersection genes were obtained by mapping and comparing with the targets of COPD.The "medicinal materials-compounds-targets model" was constructed,and the key pathways were annotated.Finally,the core target was docked with important compounds.RESULTS:A total of 8 studies were included in the Metaanalysis.The results showed that the Yinyanghuo(Herba Epimedii Brevicornus) group could significantly downregulate pro-inflammatory factors such as tumor necrosis factor-α(TNF-α) and interleukin(IL)-8 and increase the expression of anti-inflammatory factors and antioxidant factors such as IL-10 and phospho-protein kinase B(pAKT) in the COPD model(all P < 0.05).A total of 23 active components and 102 corresponding target genes of Yinyanghuo(Herba Epimedii Brevicornus) were obtained by bioinformatics technology,among which 17 compounds and 63 targets were closely related to COPD.The results of enrichment analysis mainly included TNF signaling pathway,phosphoinositide 3-kinase(PI3K)/Akt signaling pathway,cancer signaling pathway,and other inflammatory reactions,oxidative stress,and tumorrelated pathways.The molecular docking results showed that the binding energy fractions of the top five components of 24-epicampesterol with 10 core targets such as IL-6 were all less than ﹣5.0 kcal/mol,suggesting good binding ability.CONCLUSIONS:Meta-analysis and bioinformatics results indicated that the therapeutic effect of Yinyanghuo(Herba Epimedii Brevicornus) and its components on COPD might be related to antagonizing inflammation and oxidative stress.The above findings provide a preliminary basis for the development of Yinyanghuo(Herba Epimedii Brevicornus) as a natural drug for preventing and treating COPD.
基金supported by the National Natural Science Foundation of China(Nos.81874368 and 81630100)the Beijing Nova Program(No.Z181100006218001)+2 种基金the National Key Technology R&D Program(No.2015ZX 09501-004-001-008)the National Key R&D Program of China(No.2018YFC1707000)the National TCM Industry Science and Technology Program(No.201507004-4-2).
文摘Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.
基金supported by National Natural Science Foundation of China(81874368,81630100,and 81903891)Beijing Nova Program(Z181100006218001,China)+1 种基金National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(2017ZX09301022 and 2018ZX09101002-001-002,China)the Innovation Groups of the National Natural Science Foundation of China(81721002)
文摘Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs.Epimedii Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly understood.Increasing evidence has indicated that most cases of IDILI are immune mediated.Here,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome activation.ICSⅡexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome activation.Importantly,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.
文摘OBJECTIVE:To evaluate the effects of a combination of Yinyanghuo(Herba Epimedii Brevicornus)(HEB)and Cheqianzi(Semen Plantaginis)(SP)on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats(SHRs),and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor(ACE2/Ang[1-7]/Mas receptor)axis in this process.METHODS:A total of 24 SHRs were randomly assigned to three groups:SHR-control,low-dose(12.5 g/kg)and high-dose(25 g/kg)HEB+SP(HEBSP).Eight Wistar-Kyoto rats were used as normal controls.HEBSP was administered by oral gavage for 28 d.Erectile function was measured once a week using the Heaton test.After 4 weeks of treatment,the corpus cavernosum was harvested from each rat to measure nitric oxide(NO),nitric oxide synthase(e NOS)and Ang(1-7)levels,as well as ACE2,Mas receptor and neuronal nitric oxide synthase(n NOS)protein expression.RESULTS:After 4 weeks of treatment,HEBSP significantly increased erectile function in the treated group compared with SHR-control group(P<0.01).Additionally,HEBSP treatment significantly increased cavernosal levels of Ang(1-7),e NOS and NO.Moreover,HEBSP significantly elevated the expression levels of ACE2,Mas receptor and n NOS.These beneficial effects were elevated in the high-dose HEBSP group.CONCLUSION:HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang(1-7)/Mas receptor axis,e NOS and n NOS pathways.
基金Supported by the Natural Science Foundation of Liaoning Province:Functional Identification and Molecular Regulation of mi R-26b-5p Associated with Premature Ovarian Failure(No.20170540373)Jinzhou Foundation for Science and Technology:Study on the Rule and Mechanism of Prescriptions for Premature Ovarian Failure Based on Network Pharmacology,China(No.16B1G35)。
文摘OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism in a rat model of PCOS.METHODS:A network pharmacology approach involving a characteristic drug assessment,active compound and target prediction,PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS:Six networks were constructed,an active compound-target network for the ECD(C-T network),a drug-target network(D-T network),a related genes network,a targets interaction network,a key genes interaction network,and a gene-pathway network.A total of 41 compounds and 261 targets were identified for the ECD,232 PCOS-related genes,31 cogenes,and 14 pathways.These pathways may be involved in the efficacy of ECD on PCOS.The proteins most involved in the signal pathways for all targets were AKT1,IL6,INSR,ESR,and GSK3B.The AKT1 target was selected for experimental verification.Based on the Western blot and real-time PCR results,the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS:Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.
