OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloi...OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB.RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/L.TFDB(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats.CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.展开更多
Background:Resina Draconis is a traditional Chinese medicine mainly used to treat pain.However,the pharmacological mechanisms and chemical composition of Resina Draconis are not clear yet.Methods:In this study,based o...Background:Resina Draconis is a traditional Chinese medicine mainly used to treat pain.However,the pharmacological mechanisms and chemical composition of Resina Draconis are not clear yet.Methods:In this study,based on the 21 main active components of Resina Draconis previously analyzed by our group,the potential action targets of the active components were predicted and screened out by using the databases such as Swiss Target Prediction and Pharmapper.The genes corresponding to the related targets were retrieved by UniProt and GeneCards,and then the"component-target"network model was established using Cytoscape 3.9.1 software.The protein-protein interaction network was constructed by using STRING database for analysis.The STRING database was used for enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genome pathways to explore the underlying action mechanisms.Result:A total of 21 main analgesic active components of Resina Draconis and 77 intersecting targets of Resina Draconis and pain were screened out.PPI network analysis indicated that such targets as albumin(ALB),tumor necrosis factor(TNF),RAC-alpha serine/threonine-protein kinase 1(AKT1)and epidermal growth factor receptor(EGFR)might be the core targets of analgesia.Through gene ontology enrichment analysis,a total of 169 gene ontology entries were obtained(P<0.01),including 111 biological processes,31 molecular functions and 27 cellular components.Through enrichment analysis of KEGG pathways,a total of 112(P<0.01)signaling pathways were screened.Conclusion:Dracaenogenins A,Resveratrol and 7,4′-dihydroxyflavone in Resina Draconis may be the main material basis for analgesia,which can interact with multiple targets such as AlB,AKT1,TNF,and EGFR,and exerts analgesic effect through signaling pathways such as mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-Akt signaling pathway,and Rap1 signaling pathway.展开更多
基金High Level Talents Project of Affiliated Hospital of Youjiang Medical University for Nationalities:Study of Soft-Du'an Capsule's Mechanism and Efficacy of Regulating TRPV1 Pashways in Relieving Oral and Maxillofacial Trigeminal Neuralgia (No. YYFYR20213002)Innovative Group Project of Natural Science Foundation of Hubei Province:Study on the Mechanisms of Pain Signal Transduction and Drug Analgesia (No. 2020CFA025)。
文摘OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB.RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/L.TFDB(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats.CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.
基金supported by National Natural Science Foundation of China(No.82074137)Guangdong Basic and Applied Basic Research Foundation(No.2020A1515011515)Guangdong Undergraduate Innovation and Entrepreneurship Training Program(No.S202210573050).
文摘Background:Resina Draconis is a traditional Chinese medicine mainly used to treat pain.However,the pharmacological mechanisms and chemical composition of Resina Draconis are not clear yet.Methods:In this study,based on the 21 main active components of Resina Draconis previously analyzed by our group,the potential action targets of the active components were predicted and screened out by using the databases such as Swiss Target Prediction and Pharmapper.The genes corresponding to the related targets were retrieved by UniProt and GeneCards,and then the"component-target"network model was established using Cytoscape 3.9.1 software.The protein-protein interaction network was constructed by using STRING database for analysis.The STRING database was used for enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genome pathways to explore the underlying action mechanisms.Result:A total of 21 main analgesic active components of Resina Draconis and 77 intersecting targets of Resina Draconis and pain were screened out.PPI network analysis indicated that such targets as albumin(ALB),tumor necrosis factor(TNF),RAC-alpha serine/threonine-protein kinase 1(AKT1)and epidermal growth factor receptor(EGFR)might be the core targets of analgesia.Through gene ontology enrichment analysis,a total of 169 gene ontology entries were obtained(P<0.01),including 111 biological processes,31 molecular functions and 27 cellular components.Through enrichment analysis of KEGG pathways,a total of 112(P<0.01)signaling pathways were screened.Conclusion:Dracaenogenins A,Resveratrol and 7,4′-dihydroxyflavone in Resina Draconis may be the main material basis for analgesia,which can interact with multiple targets such as AlB,AKT1,TNF,and EGFR,and exerts analgesic effect through signaling pathways such as mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-Akt signaling pathway,and Rap1 signaling pathway.
