Objective:To study the mechanism of Yuanhuzhitong decoction for the treatment of osteoarthritis from the perspective of network pharmacology.Methods:The active ingredients of Yuanhuzhitong decoction were screened out ...Objective:To study the mechanism of Yuanhuzhitong decoction for the treatment of osteoarthritis from the perspective of network pharmacology.Methods:The active ingredients of Yuanhuzhitong decoction were screened out from the TCMSP database,and then the targets of the active ingredients were extracted.The drug-ingredient-target network was constructed using Cytoscape software.The genes of osteoarthritis were obtained by OMIM,GeneCards and DisGeNET databases.Drug targets and disease targets were mapped together,and the relationship of the key target protein-protein interaction(PPI)was obtained through the online STRING database.Key targets were analyzed by Clue GO plug-in for GO functional enrichment and KEGG signaling pathway enrichment.Results:A total of 71 active ingredients and 99 unique targets of alkaloids,coumarins,volatile oils,steroids,etc were obtained through the threshold of OB 30%and DL 0.18.45 common targets were obtained through Venn diagram,among which the core targets were IL6,VEGFA,CASP3,CCND1,ESR1,etc.GO enrichment analysis revealed that the biological processes of Yuanhuzhitong decoction for OA were mainly concentrated in cell migration,differentiation,nucleotide metabolism and synthesis,regulation of pri-miRNA transcription by RNA polymerase II,and apoptosis.KEGG analysis showed that Yuanhuzhitong decoction may act on HIF-1 signal pathway,TNF signal pathway,NF-κB signal pathway and other pathways.The results showed that the main active ingredients in Yuanhuzhitong decoction could play an important role for the treatment of osteoarthritis through"multi-component,multi-target and multi-pathway".Conclusion:This study analyzed the main active ingredients,key targets,signaling pathways and mechanism of Yuanhuzhitong decoction from the perspective of network pharmacology,laying a foundation for further exploration of its mechanism.展开更多
Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy,while the mechanism was not very clear.Here,the authors ...Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy,while the mechanism was not very clear.Here,the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3,the liver transporters OATP1 B1 and OATP1 B3,and the intestine transporter OATP2 B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation(YHP)comprising Corydalis yanhusuo(CYH)and Angelica dahurica(AD),which could relieve pain by restraining the central system.The results show that tetrahydropalmatine(TDE),the major component of CYH,could be transported by OAT3 into kidney,OATP1 B1 and OATP1 B3 into liver,while imperatorin(IPT)and isoimperatorin(ISP),the two key components of AD,and AD extract showed strong inhibition to OAT1 and OAT3.What’s more,AD extract also exerted strongly inhibition to human transporters OATP1 B1 and OATP1 B3.It was also detected that IPT,ISP,and AD extract significantly downregulated the expression of Oatplal,Oafp1 a4,and Oatp1 b2 of liver in mice.The in vivo results show that the concentration of TDE in liver and kidney significantly decreased,while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT,ISP,and AD extract.These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney.That is to say,TDE with bitter taste could"flood up"into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD.This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3,OATP1 B1,and OATP1 B3,but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD.This study may offer a valuable clue to illustrate the mechanism of compatibility theory.展开更多
基金Capacity building project of Chinese and western medicine clinical collaboration on major difficult disease in 2019-Stepwise therapies of integrated Chinese and western medicine for knee osteoarthritis.
文摘Objective:To study the mechanism of Yuanhuzhitong decoction for the treatment of osteoarthritis from the perspective of network pharmacology.Methods:The active ingredients of Yuanhuzhitong decoction were screened out from the TCMSP database,and then the targets of the active ingredients were extracted.The drug-ingredient-target network was constructed using Cytoscape software.The genes of osteoarthritis were obtained by OMIM,GeneCards and DisGeNET databases.Drug targets and disease targets were mapped together,and the relationship of the key target protein-protein interaction(PPI)was obtained through the online STRING database.Key targets were analyzed by Clue GO plug-in for GO functional enrichment and KEGG signaling pathway enrichment.Results:A total of 71 active ingredients and 99 unique targets of alkaloids,coumarins,volatile oils,steroids,etc were obtained through the threshold of OB 30%and DL 0.18.45 common targets were obtained through Venn diagram,among which the core targets were IL6,VEGFA,CASP3,CCND1,ESR1,etc.GO enrichment analysis revealed that the biological processes of Yuanhuzhitong decoction for OA were mainly concentrated in cell migration,differentiation,nucleotide metabolism and synthesis,regulation of pri-miRNA transcription by RNA polymerase II,and apoptosis.KEGG analysis showed that Yuanhuzhitong decoction may act on HIF-1 signal pathway,TNF signal pathway,NF-κB signal pathway and other pathways.The results showed that the main active ingredients in Yuanhuzhitong decoction could play an important role for the treatment of osteoarthritis through"multi-component,multi-target and multi-pathway".Conclusion:This study analyzed the main active ingredients,key targets,signaling pathways and mechanism of Yuanhuzhitong decoction from the perspective of network pharmacology,laying a foundation for further exploration of its mechanism.
基金supported by the National Natural Science Foundation of China(grant Nos.81430096 and 81503154)Tianjin Science and Technology Support Key Projects(grant No.17YFZCSY01170,China)Research Unit for Drug Metabolism,Chinese Academy of Medical Sciences(grant No.2019RU009,China)
文摘Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy,while the mechanism was not very clear.Here,the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3,the liver transporters OATP1 B1 and OATP1 B3,and the intestine transporter OATP2 B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation(YHP)comprising Corydalis yanhusuo(CYH)and Angelica dahurica(AD),which could relieve pain by restraining the central system.The results show that tetrahydropalmatine(TDE),the major component of CYH,could be transported by OAT3 into kidney,OATP1 B1 and OATP1 B3 into liver,while imperatorin(IPT)and isoimperatorin(ISP),the two key components of AD,and AD extract showed strong inhibition to OAT1 and OAT3.What’s more,AD extract also exerted strongly inhibition to human transporters OATP1 B1 and OATP1 B3.It was also detected that IPT,ISP,and AD extract significantly downregulated the expression of Oatplal,Oafp1 a4,and Oatp1 b2 of liver in mice.The in vivo results show that the concentration of TDE in liver and kidney significantly decreased,while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT,ISP,and AD extract.These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney.That is to say,TDE with bitter taste could"flood up"into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD.This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3,OATP1 B1,and OATP1 B3,but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD.This study may offer a valuable clue to illustrate the mechanism of compatibility theory.
