Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)combination and toxicity reduction of Chuan-wu combined with Gancao(Glycyrrhizae Radix et Rh...Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)combination and toxicity reduction of Chuan-wu combined with Gancao(Glycyrrhizae Radix et Rhizoma)in Wutou Decoction(乌头汤,WTD),and to elucidate the compatibility principle.Methods The active compounds and potential effective targets of the selected combinations were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID).The toxicity of Chuanwu(Aconiti Radix)was investigated by selecting all five toxic compounds from the literature and the TCMSP database,and obtaining their targets through SwissTargetPrediction.Targets related to rheumatoid arthritis(RA)were searched using Dis-GeNET,GenCards,and Online Mendelian Inheritance in Man(OMIM).Mutual targets between the drug pairs and RA were selected as potential RA therapy targets.The medicinally active compound-target network was constructed using Cytoscape 3.9.0.Gene ontology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrich-ment were performed using the Database for Annotation,Visualization,and Integrated Dis-covery(DAVID)platform.Results We obtained 191 active compound targets for Gancao(Glycyrrhizae Radix et Rhizoma),171 for Huangqi(Astragali Radix),and 103 for Chuanwu(Radix Aconiti)(hypo-aconitine’s target was obtained through literature and SwissTargetPrediction).A total of 5872 genes were obtained for RA.A drug-active compound-target network involving 13 effect-en-hancing and nine toxicity reduction targets was constructed.PGR was the main effect en-hancement target,and KCNH2 was the main toxicity reduction target.The effect-enhancing targets were related to 23 GO terms(such as positive regulation of transcription from RNA polymerase II promoter,steroid hormone-mediated signaling pathway,plasma membrane,and protein binding)(P<0.01),and 13 KEGG pathways related to synergism[such as estro-gen signaling pathway,cholinergic synapse,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway].The toxicity reduction targets were related to 28 GO terms(mainly involes G-protein coupled receptor signaling pathway,plasma membrane,and drug binding)(P<0.01),and five KEGG pathways related to toxicity reduction(cholinergic syn-apse,calcium signaling pathway,regulation of actin cytoskeleton,neuroactive ligand-recept-or interaction,and serotonergic synapse).Conclusion The combination of Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)plays an important effect-enhancing role in WTD and involves the estrogen and PI3K/Akt sig-naling pathways,with PGR as the core.The Chuanwu(Aconiti Radix)and Gancao(Gly-cyrrhizae Radix et Rhizoma)combination decreases toxicity in WTD and is associated with the cholinergic synapse and calcium signaling pathways,with KCNH2 as the core.展开更多
BuGuZhi (Psoraleae Fructus) is the dry mature peel of the leguminous plant. After ripening in autumn, the fruit is collected and dried to get its fruit, which has the effect of warming kidney and helping Yang, t...BuGuZhi (Psoraleae Fructus) is the dry mature peel of the leguminous plant. After ripening in autumn, the fruit is collected and dried to get its fruit, which has the effect of warming kidney and helping Yang, the effect of absorbing asthma, warming the kidney and relieving diarrhea, and treating vitiligo and alopecia. Because the clinical curative effect is exact, so it has been widely used in the treatment of clinical diseases. However, the recent reports and clinical cases reported that BuGuZhi has some toxic effects. According to domestic and foreign references, toxic effects are mainly divided into hepatotoxicity, nephrotoxicity, phototoxicity, reproductive toxicity, and rare cases of retinal vagueness reported by clinical reports. the toxicity of BuGuZhi is summarized. The article analyzed the way of synergism and reduction of BuGuZhi, which was based on data mainly coming from the compatibility of drugs, pattern identification, constitution identification and drug processing. All o-f analyses and summaries are in order to make the clinical medication safer and more scientific.展开更多
基金Macao Science and Technology Development Fund(0003/2019/AKP and 0010/2020/A1)Guangdong Basic and Applied Basic Research Foundation(2020B1515130005)+1 种基金Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research,Guangzhou University of Chinese Medicine(2020B1212030006)supported by a grant from the“Macao Young Scholars Program”(AM2020017).
文摘Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)combination and toxicity reduction of Chuan-wu combined with Gancao(Glycyrrhizae Radix et Rhizoma)in Wutou Decoction(乌头汤,WTD),and to elucidate the compatibility principle.Methods The active compounds and potential effective targets of the selected combinations were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID).The toxicity of Chuanwu(Aconiti Radix)was investigated by selecting all five toxic compounds from the literature and the TCMSP database,and obtaining their targets through SwissTargetPrediction.Targets related to rheumatoid arthritis(RA)were searched using Dis-GeNET,GenCards,and Online Mendelian Inheritance in Man(OMIM).Mutual targets between the drug pairs and RA were selected as potential RA therapy targets.The medicinally active compound-target network was constructed using Cytoscape 3.9.0.Gene ontology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrich-ment were performed using the Database for Annotation,Visualization,and Integrated Dis-covery(DAVID)platform.Results We obtained 191 active compound targets for Gancao(Glycyrrhizae Radix et Rhizoma),171 for Huangqi(Astragali Radix),and 103 for Chuanwu(Radix Aconiti)(hypo-aconitine’s target was obtained through literature and SwissTargetPrediction).A total of 5872 genes were obtained for RA.A drug-active compound-target network involving 13 effect-en-hancing and nine toxicity reduction targets was constructed.PGR was the main effect en-hancement target,and KCNH2 was the main toxicity reduction target.The effect-enhancing targets were related to 23 GO terms(such as positive regulation of transcription from RNA polymerase II promoter,steroid hormone-mediated signaling pathway,plasma membrane,and protein binding)(P<0.01),and 13 KEGG pathways related to synergism[such as estro-gen signaling pathway,cholinergic synapse,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway].The toxicity reduction targets were related to 28 GO terms(mainly involes G-protein coupled receptor signaling pathway,plasma membrane,and drug binding)(P<0.01),and five KEGG pathways related to toxicity reduction(cholinergic syn-apse,calcium signaling pathway,regulation of actin cytoskeleton,neuroactive ligand-recept-or interaction,and serotonergic synapse).Conclusion The combination of Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)plays an important effect-enhancing role in WTD and involves the estrogen and PI3K/Akt sig-naling pathways,with PGR as the core.The Chuanwu(Aconiti Radix)and Gancao(Gly-cyrrhizae Radix et Rhizoma)combination decreases toxicity in WTD and is associated with the cholinergic synapse and calcium signaling pathways,with KCNH2 as the core.
文摘BuGuZhi (Psoraleae Fructus) is the dry mature peel of the leguminous plant. After ripening in autumn, the fruit is collected and dried to get its fruit, which has the effect of warming kidney and helping Yang, the effect of absorbing asthma, warming the kidney and relieving diarrhea, and treating vitiligo and alopecia. Because the clinical curative effect is exact, so it has been widely used in the treatment of clinical diseases. However, the recent reports and clinical cases reported that BuGuZhi has some toxic effects. According to domestic and foreign references, toxic effects are mainly divided into hepatotoxicity, nephrotoxicity, phototoxicity, reproductive toxicity, and rare cases of retinal vagueness reported by clinical reports. the toxicity of BuGuZhi is summarized. The article analyzed the way of synergism and reduction of BuGuZhi, which was based on data mainly coming from the compatibility of drugs, pattern identification, constitution identification and drug processing. All o-f analyses and summaries are in order to make the clinical medication safer and more scientific.