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
Commiphoroids G_(1)-G_(3),H and I(1-5),five new terpenoid dimers were isolated from Resina Commiphora.Their structures and absolute configurations were determined by using spectroscopic,computational and crystallograp...Commiphoroids G_(1)-G_(3),H and I(1-5),five new terpenoid dimers were isolated from Resina Commiphora.Their structures and absolute configurations were determined by using spectroscopic,computational and crystallographic methods.Biological evaluation of these terpenoid dimers against renal fibrosis reveals that 5 inhibits extracellular matrix components including fibronectin and colla-gen I in a concentration-dependent manner.展开更多
目的 基于网络药理学阐释血竭-青黛配伍治疗糖尿病皮肤创面的药效物质基础及作用机制。方法 通过检索中药系统药理学分析平台(traditional Chinese medicine systematic pharmacology platform, TCMSP)、有机小分子生物活性数据库(PubCh...目的 基于网络药理学阐释血竭-青黛配伍治疗糖尿病皮肤创面的药效物质基础及作用机制。方法 通过检索中药系统药理学分析平台(traditional Chinese medicine systematic pharmacology platform, TCMSP)、有机小分子生物活性数据库(PubChem),筛选血竭、青黛的活性成分及作用靶点。利用疾病基因数据库获得糖尿病皮肤创面相关靶点,分析血竭、青黛活性成分靶点与糖尿病皮肤创面疾病靶点的交集即为潜在作用靶点,并构建“血竭、青黛-活性成分-潜在作用靶点”网络。构建靶点间的蛋白相互作用(protein-protein interaction, PPI)网络,对潜在作用靶点基因进行基因本体(gene ontology, GO)富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析。结果 收集血竭-青黛药对的有效活性成分15个,包括双靛蓝素、尿蓝母等,发现血竭-青黛与糖尿病皮肤创面交集靶点共139个,血竭-青黛促进糖尿病皮肤创面愈合Cytoscape网络分析发现RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase, AKT1)、肿瘤坏死因子(tumor necrosis factor, TNF)等10个核心靶点,靶点主要富集在动脉粥样硬化信号通路、蛋白质糖基化产物与其受体(advanced glycation end products-receptor for advanced glycation end products, AGE-RAGE)信号通路等相关通路。结论 血竭-青黛药对可能通过血管再生、氧化还原、炎症反应、脂类与动脉粥样硬化信号通路、AGE-RAGE信号通路、化学致癌受体激活通路调节糖尿病皮肤创面愈合进程。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.
基金This study was supported financially by the National Science Fund for Distinguished Young Scholars(No.81525026)the National Key R&D Program of China(No.2017YFA0503900)+3 种基金the She nzhe n Fundame ntal Research Program(No.JCYJ20200109114003921)the SZU Top Ranking Project(No.86000000210)the Natural Science Research Project of Shenzhen University(2019122)the SZU Medical Young Scientist Program.
文摘Commiphoroids G_(1)-G_(3),H and I(1-5),five new terpenoid dimers were isolated from Resina Commiphora.Their structures and absolute configurations were determined by using spectroscopic,computational and crystallographic methods.Biological evaluation of these terpenoid dimers against renal fibrosis reveals that 5 inhibits extracellular matrix components including fibronectin and colla-gen I in a concentration-dependent manner.
文摘目的探讨龙血竭联合氟尿嘧啶注射液对不同转化生长因子-β(Transforming growth factor-β,TGF-β)单核苷酸多态性瘢痕疙瘩患者的疗效。方法纳入2019年7月—2022年1月医院收治的瘢痕疙瘩患者240例,根据TGF-β单核苷酸多态分为野生组(野生型TGF-β)、突变组(突变型TGF-β),并将突变组分为亚组:rs747857组(rs747857型TGF-β)、rs1800469组(rs1800469型TGF-β)、rs2241716组(rs2241716型TGF-β)。使用氟尿嘧啶注射液单药治疗或血竭联合氟尿嘧啶注射液治疗5组患者。5组患者治疗前和首次治疗后12个月通过温哥华瘢痕量表(Vancouver scar scale,VSS)、瘢痕评估量表(Patient and observer scar assessment scale,POSAS)和皮肤病生活质量指数(Dermatologic quality of life index,DLQI)量表进行评分。结果与野生组比较,突变组、rs747857组、rs1800469组、rs2241716组TGF-βmRNA的表达水平均上升(P<0.05)。与野生组相比,单药治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著上升(P<0.05);而与单药治疗相比,联合治疗下突变组、rs1800469组和rs2241716组患者在治疗后VSS总评分、POSAS总评分均显著下降(P<0.05)。与野生组相比,rs2241716组患者在治疗后的DLQI量表评分均显著上升(P<0.05);而与单药治疗相比,联合治疗下rs2241716组患者在治疗后的DLQI量表评分均显著下降(P<0.05)。与野生组相比,rs1800469组和rs2241716组患者在治疗后的有效率显著下降(P<0.05);而与单药治疗相比,联合治疗下rs1800469组和rs2241716组患者在治疗后的有效率显著上升(P<0.05)。与野生组相比,突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均延后(P<0.05);而与单药治疗相比,联合治疗下突变组、rs1800469组和rs2241716组患者的首次显效及达到首次显效时氟尿嘧啶次数均提前(P<0.05)。与单药治疗相比,联合治疗下野生组、突变组、rs747857组、rs1800469组、rs2241716组的总不良反应更少(P<0.05)。结论龙血竭联合氟尿嘧啶注射液对不同TGF-β单核苷酸多态性瘢痕疙瘩患者有较好的疗效,和较少的不良反应。
文摘采用网络药理学、分子对接和实验验证研究龙血竭促进糖尿病足创面愈合的作用机制。利用TCMSP数据库,筛选龙血竭的化学成分及作用靶标;以“diabetic foot ulcer”“diabetic wound”等为关键词在GeneCards和DisGeNET数据库中检索疾病靶点;取龙血竭成分靶点与疾病靶点交集,构建“成分-疾病-靶标”网络图;生信分析预测龙血竭促进创面愈合的作用机制;采用分子对接考察龙血竭成分与关键靶点的结合情况;采用小鼠巨噬细胞,研究龙血竭及其主要成分对晚期糖基化终产物受体(the receptor of advanced glycation end products,RAGE)蛋白表达的影响。结果表明:网络药理学筛选得到226个化合物疾病共同靶标;KEGG富集分析提示,龙血竭治疗糖尿病足创面的作用可能与AGE-RAGE信号通路密切相关。分子对接结果显示,龙血素A、龙血素B、龙血素C、龙血素D、白藜芦醇、7,4′-二羟基黄酮6个成分与RAGE之间均有较好的结合活性。龙血竭及其主要成分均能显著逆转晚期糖基化终末产物(AGEs)引起的小鼠巨噬细胞RAGE蛋白异常表达。综上,龙血竭促进糖尿病足创面愈合与其调控AGE-RAGE通路,抑制AGEs累积引起RAGE蛋白异常表达相关。
