Objective To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome(CARAS)with lung-spleen qi deficiency and wind-cold invading the lung syndrome using network pharm...Objective To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome(CARAS)with lung-spleen qi deficiency and wind-cold invading the lung syndrome using network pharmacology and molecular docking.MethodsThe active components and targets of the 13 herbs in Fuzheng Gankang Pill were retrieved from the TraditionalChinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and HERB.A“core herb-active component-target"network was constructed using Cytoscape to screen core components.CARAS disease targets were obtained from Genecards,NationalCenter for Biotechnology Information(NCBI),and Online Mendelian Inheritance in Man(OMIM).Targets related to the clinical phenotypes of CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome were retrieved from the Traditional ChineseMedicineSyndrome Ontology and Multidimensional Quantitative Association Calculation Platform.The intersection of CARAS disease targets and syndromerelated targets yielded CARAS disease-syndrome targets.The intersection of Fuzheng Gankang Pill component-related targets and CARAS disease-syndrome targets provided“disease-syndrome-formula”intersection targets.These targets were uploaded to the STRING database for protein-protein interaction(PPI)network analysis,with topological analysis identifying key targets.Metascape was used for Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Vina 1.1.2.Results The 13 core herbs of Fuzheng Gankang Pill contain a total of 200 active ingredients and 289 related targets.There are 2,412 disease targets for CARAS and 735 corresponding disease targets for the main and secondary symptoms of lung-spleen qi deficiency and wind-cold invading the lung.Through the Venn diagram,a total of 35 intersecting targets were obtained for Fuzheng Gankang Pill,CARAS,and the combination of lung-spleen qi deficiency and wind-cold invading the lung syndrome.Quercetin,Polygonatum sibiricum flavonoids,β-sitosterol,baicalein,kaempferol,etc.,are core components.PPI network analysis found that tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),interleukin(IL)-1β,IL-6,transforming growth factor beta 1(TGFβ1),BCL2,etc.,are the core targets for the compound to exert therapeutic effects.GO enrichment analysis showed that the 13 core drugs of Fuzheng Gankang Pill mainly participate in key biological processes such as positive regulation of protein modification,response to hormones,and negative regulation of cell population proliferation through protein kinases in areas such as membrane rafts,membrane microregions,plasma membrane protein complexes,and receptor com-plexes.KEGG enriched a total of 30 signaling pathways.Molecular docking shows that active ingredients such as quercetin and kaempferol bind stably toTNF(binding energy≤-9.0 kcal·mol^(-1))and PTGS2(≤-8.5kcal·mol^(-1)).Conclusion Fuzheng Gankang Pill may regulate biological processes such as cell apoptosis,tissue remodeling,inflammatory response,and immune response by acting on core targets such as TNF and PTGS2 through its core components quercetin,baicalein,β-sitosterol,baicalein,and kaempferol,thereby exerting therapeutic effects on CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome.展开更多
To examine the effect of Gankang Suppository on duck hepatitis B virus （DHBV）, the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infectin...To examine the effect of Gankang Suppository on duck hepatitis B virus （DHBV）, the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infecting 1-day-old Yingtaogu ducklings with DHBV-positive serum. The successful model was confirmed by PCR assay and 48 ducklings infected with DHBV were randomly divided into 3 groups： a Gankang Suppository treatment group, an acyclovir （ACV） group and a DHBV model group （control）, with each group having 16 animals. All the animals were given the medicines for 4 weeks in a row. The serum of the animals was taken 14 and 28 days after the medica- tion and 7 days after drug discontinuation. Real-time PCR was performed to detect the copy numbers of DHBV DNA in the serum. ALT and AST were dynamically monitored. The ducklings were sacrificed on the 7th day after the discontinuation of the treatment and livers were harvested and examined for inflammation and degeneration of liver cells by using HE staining. The results showed that on day 14, 28 after the treatment and day 7 after the withdrawal, the logarithmic values （log） of DHBV DNA copy numbers in ducklings of Gankang Suppository treatment group were significantly lower than that before the treatment （P=0.0092, P=0.0070, P=0.0080, respectively）. Compared with DHBV model control group, the ALT level was significantly decreased （P=0.0020, P=0.0019, respectively） on day 28 after the treatment and on day 7 after the withdrawal. The AST level was also reduced on day 14 after the treatment （P=0.0298）. Compared with the ACV control group, the level of ALT was lower on day 7 after the withdrawal （P=0.0016）. Histologically, the hepatocyte swelling, vacuolous degeneration and acidophilic degeneration in Gankang Suppository treatment group were alleviated 7 days after the withdrawal as compared with model control group （P=0.0282, P=0.0084, P=0.0195, respectively）. It is concluded that Gankang Suppository can effectively suppress DHBV replication, reduce the levels of serum ALT and AST and improve hepatic histology.展开更多
基金supported by Special Project of Traditional Chinese Medicine Scientific Research in Henan Province(2023ZY1024,2022ZY1144)Special COVID-19 Research Project of Traditional Chinese Medicine in Henan Province(2022ZYFY08)+1 种基金Traditional Chinese Medicine Culture and Management Research Project in Henan Province(TCM2023005)Basic Scientific Research Business Fund Project of Henan Integrative Medicine Hospital(2304025,2304015)。
文摘Objective To elucidate the mechanism of Fuzheng Gankang Pill in treating combined allergic rhinitis and asthma syndrome(CARAS)with lung-spleen qi deficiency and wind-cold invading the lung syndrome using network pharmacology and molecular docking.MethodsThe active components and targets of the 13 herbs in Fuzheng Gankang Pill were retrieved from the TraditionalChinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and HERB.A“core herb-active component-target"network was constructed using Cytoscape to screen core components.CARAS disease targets were obtained from Genecards,NationalCenter for Biotechnology Information(NCBI),and Online Mendelian Inheritance in Man(OMIM).Targets related to the clinical phenotypes of CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome were retrieved from the Traditional ChineseMedicineSyndrome Ontology and Multidimensional Quantitative Association Calculation Platform.The intersection of CARAS disease targets and syndromerelated targets yielded CARAS disease-syndrome targets.The intersection of Fuzheng Gankang Pill component-related targets and CARAS disease-syndrome targets provided“disease-syndrome-formula”intersection targets.These targets were uploaded to the STRING database for protein-protein interaction(PPI)network analysis,with topological analysis identifying key targets.Metascape was used for Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Vina 1.1.2.Results The 13 core herbs of Fuzheng Gankang Pill contain a total of 200 active ingredients and 289 related targets.There are 2,412 disease targets for CARAS and 735 corresponding disease targets for the main and secondary symptoms of lung-spleen qi deficiency and wind-cold invading the lung.Through the Venn diagram,a total of 35 intersecting targets were obtained for Fuzheng Gankang Pill,CARAS,and the combination of lung-spleen qi deficiency and wind-cold invading the lung syndrome.Quercetin,Polygonatum sibiricum flavonoids,β-sitosterol,baicalein,kaempferol,etc.,are core components.PPI network analysis found that tumor necrosis factor(TNF),prostaglandin-endoperoxide synthase 2(PTGS2),interleukin(IL)-1β,IL-6,transforming growth factor beta 1(TGFβ1),BCL2,etc.,are the core targets for the compound to exert therapeutic effects.GO enrichment analysis showed that the 13 core drugs of Fuzheng Gankang Pill mainly participate in key biological processes such as positive regulation of protein modification,response to hormones,and negative regulation of cell population proliferation through protein kinases in areas such as membrane rafts,membrane microregions,plasma membrane protein complexes,and receptor com-plexes.KEGG enriched a total of 30 signaling pathways.Molecular docking shows that active ingredients such as quercetin and kaempferol bind stably toTNF(binding energy≤-9.0 kcal·mol^(-1))and PTGS2(≤-8.5kcal·mol^(-1)).Conclusion Fuzheng Gankang Pill may regulate biological processes such as cell apoptosis,tissue remodeling,inflammatory response,and immune response by acting on core targets such as TNF and PTGS2 through its core components quercetin,baicalein,β-sitosterol,baicalein,and kaempferol,thereby exerting therapeutic effects on CARAS with lung-spleen qi deficiency and wind-cold invading the lung syndrome.
基金the National Natural Science Foundation of China (No. 30471533)
文摘To examine the effect of Gankang Suppository on duck hepatitis B virus （DHBV）, the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infecting 1-day-old Yingtaogu ducklings with DHBV-positive serum. The successful model was confirmed by PCR assay and 48 ducklings infected with DHBV were randomly divided into 3 groups： a Gankang Suppository treatment group, an acyclovir （ACV） group and a DHBV model group （control）, with each group having 16 animals. All the animals were given the medicines for 4 weeks in a row. The serum of the animals was taken 14 and 28 days after the medica- tion and 7 days after drug discontinuation. Real-time PCR was performed to detect the copy numbers of DHBV DNA in the serum. ALT and AST were dynamically monitored. The ducklings were sacrificed on the 7th day after the discontinuation of the treatment and livers were harvested and examined for inflammation and degeneration of liver cells by using HE staining. The results showed that on day 14, 28 after the treatment and day 7 after the withdrawal, the logarithmic values （log） of DHBV DNA copy numbers in ducklings of Gankang Suppository treatment group were significantly lower than that before the treatment （P=0.0092, P=0.0070, P=0.0080, respectively）. Compared with DHBV model control group, the ALT level was significantly decreased （P=0.0020, P=0.0019, respectively） on day 28 after the treatment and on day 7 after the withdrawal. The AST level was also reduced on day 14 after the treatment （P=0.0298）. Compared with the ACV control group, the level of ALT was lower on day 7 after the withdrawal （P=0.0016）. Histologically, the hepatocyte swelling, vacuolous degeneration and acidophilic degeneration in Gankang Suppository treatment group were alleviated 7 days after the withdrawal as compared with model control group （P=0.0282, P=0.0084, P=0.0195, respectively）. It is concluded that Gankang Suppository can effectively suppress DHBV replication, reduce the levels of serum ALT and AST and improve hepatic histology.
