Objective To explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong(Chuanxiong Rhizoma)-Suhexiang(Styrax)-Bingpian(Borneolum)(hereinafter referred to as C-S-B volatile oil)i...Objective To explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong(Chuanxiong Rhizoma)-Suhexiang(Styrax)-Bingpian(Borneolum)(hereinafter referred to as C-S-B volatile oil)in treating angina pectoris based on network pharmacology and to detect its protective effects against rat myocardial damage.Methods Gas chromatography-mass spectrometry(GC-MS)was used to determine the constituents of volatile oils from Chuanxiong(Chuanxiong Rhizoma),Suhexiang(Styrax),and Bingpian(Borneolum),and the targets of the three main constituents were found predicted and screened using the PharmMapper server,and Gene Cards and Coo LGe N databases.The STRING database and Cytoscape software were used to draw the protein-protein interaction(PPI)network,RStudio software was used to analyze Gene Ontology(GO)and Kyoto Encyclopedia of Genome and Genome(KEGG)pathways,and Cytoscape software was used to construct the component-target-pathwaydisease network.The rat model of myocardial injury was established by intraperitoneal injection of a large dose of isoprenaline hydrochloride.After continuous intervention with C-S-B volatile oil for 14 d,the ejection fraction(EF)and short axis shortening rate(FS)of the left ventricle were detected.The indices of myocardial damage were detected after hematoxylin-eosin(HE)staining.Results Fifteen volatile oil components from the C-S-B formula were identified.There are 470 targets of these volatile oil components and 401 angina-related genes.There are 28 core targets,including CHRM4,ADRA1 A,FGFR1,CHRM2,CYP2 A6,CHRM5,CHRM1,CHRM3,HDAC2,and MPO,etc..The results of the KEGG analysis indicated that the C-S-B formula probably interferes with the following pathways:neuroactive ligand-receptor interactions,calcium signaling,cytochrome P450 metabolism of heteropoietin,among others.The results of animal experiments showed that the C-S-B formula essential oil could significantly improve the following myocardial indices in rats with myocardial injury:EF,FS,left ventricular end-systolic diameter(LVIDs),left ventricular end-diastolic diameter(LVIDd),and stroke volume(SV),and all the differences were statistically significant(P<0.01).Conclusion The mechanism of action of volatile oil components in the C-S-B formula in treating angina pectoris was analyzed using multi-component,multi-target and multi-pathway systems,which has laid a foundation for further revealing its mechanism of action.Animal experiments have shown that the volatile oil of the C-S-B formula can improve EF,FS,and other indices of myocardial damage in a rat model,thus relieving myocardial damage caused by heart hyperactivity,improving cardiac function,and protecting against myocardial damage.展开更多
OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of(+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millennia.However,the clinical efficacy...OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of(+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millennia.However,the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topical bingpian in humans,and elucidated the underling mechanisms in animal models of pain.METHODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital.Capsaicin,formalin,CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging,patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells.RESULTS(1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized,double-blind,placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice.(3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia.(4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.展开更多
基金funding support from the Major Science and Technology Research and Development Special Project of Jiangxi Science and Technology Department(No.20194ABC28009)National Key Research and Development Plan(No.2018YFC1706404)。
文摘Objective To explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong(Chuanxiong Rhizoma)-Suhexiang(Styrax)-Bingpian(Borneolum)(hereinafter referred to as C-S-B volatile oil)in treating angina pectoris based on network pharmacology and to detect its protective effects against rat myocardial damage.Methods Gas chromatography-mass spectrometry(GC-MS)was used to determine the constituents of volatile oils from Chuanxiong(Chuanxiong Rhizoma),Suhexiang(Styrax),and Bingpian(Borneolum),and the targets of the three main constituents were found predicted and screened using the PharmMapper server,and Gene Cards and Coo LGe N databases.The STRING database and Cytoscape software were used to draw the protein-protein interaction(PPI)network,RStudio software was used to analyze Gene Ontology(GO)and Kyoto Encyclopedia of Genome and Genome(KEGG)pathways,and Cytoscape software was used to construct the component-target-pathwaydisease network.The rat model of myocardial injury was established by intraperitoneal injection of a large dose of isoprenaline hydrochloride.After continuous intervention with C-S-B volatile oil for 14 d,the ejection fraction(EF)and short axis shortening rate(FS)of the left ventricle were detected.The indices of myocardial damage were detected after hematoxylin-eosin(HE)staining.Results Fifteen volatile oil components from the C-S-B formula were identified.There are 470 targets of these volatile oil components and 401 angina-related genes.There are 28 core targets,including CHRM4,ADRA1 A,FGFR1,CHRM2,CYP2 A6,CHRM5,CHRM1,CHRM3,HDAC2,and MPO,etc..The results of the KEGG analysis indicated that the C-S-B formula probably interferes with the following pathways:neuroactive ligand-receptor interactions,calcium signaling,cytochrome P450 metabolism of heteropoietin,among others.The results of animal experiments showed that the C-S-B formula essential oil could significantly improve the following myocardial indices in rats with myocardial injury:EF,FS,left ventricular end-systolic diameter(LVIDs),left ventricular end-diastolic diameter(LVIDd),and stroke volume(SV),and all the differences were statistically significant(P<0.01).Conclusion The mechanism of action of volatile oil components in the C-S-B formula in treating angina pectoris was analyzed using multi-component,multi-target and multi-pathway systems,which has laid a foundation for further revealing its mechanism of action.Animal experiments have shown that the volatile oil of the C-S-B formula can improve EF,FS,and other indices of myocardial damage in a rat model,thus relieving myocardial damage caused by heart hyperactivity,improving cardiac function,and protecting against myocardial damage.
基金supported by National Natural Science Foundation of ChinaYunnan Applied Basic Research Projects
文摘OBJECTIVE Bingpian is an almost pure chemical with a chemical composition of(+)-borneol and has been historically used as a topical analgesic in traditional Chinese medicine for millennia.However,the clinical efficacy of topical bingpian lacks stringent evidence-based clinical studies and the underlying molecular mechanisms are unclear.This study verified the analgesic efficacy of topical bingpian in humans,and elucidated the underling mechanisms in animal models of pain.METHODS The analgesic efficacy of topical bingpian was examined in a randomized,double-blind,placebo-controlled clinical study at the Shanghai Changzheng Hospital.Capsaicin,formalin,CFA or thermal caused pain/hyperalgesia were established in different mouse models,and bingpian-induced analgesia and the underlying mechanisms were studied in these models.The molecular targets of bingpian were examined by calcium imaging,patch-clamp recording and enzymatic activity assay in mouse sensory neurons or transfected HEK 293 cells.RESULTS(1)Topical application of bingpian leads to significantly greater pain relief than placebo does in a randomized,double-blind,placebo-controlled clinical study involving 122 patients with postoperative pain.(2)TRPM8 channel is the most sensitive molecular target of bingpian and mediates topical bingpian-induced analgesia in mice.(3)A downstream glutamatergic mechanism in the spinal cord contributes to topical bingpian-induced analgesia.(4)Bingpian shows mechanistic differences and advantages as a topical analgesic when compared with menthol.
