Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide.Influenza A virus(IAV)has been found to activate multiple programmed cell death pathways,including ferroptosis.F...Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide.Influenza A virus(IAV)has been found to activate multiple programmed cell death pathways,including ferroptosis.Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation,leading to cell death.However,little is known about how influenza viruses induce ferroptosis in the host cells.In this study,based on network pharmacology,we predicted the mechanism of action of Maxing Shigan decoction(MXSGD)in IAV-induced ferroptosis,and found that this process was related to biological processes,cellular components,molecular function and multiple signaling pathways,where the hypoxia inducible factor-1(HIF-1)signaling pathway plays a significant role.Subsequently,we constructed the mouse lung epithelial(MLE-12)cell model by IAV-infected in vitro cell experiments,and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage,increased reactive oxygen species(ROS)release,increased total iron and iron ion contents,decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4(GPX4),increased expression of acyl-CoA synthetase long chain family member 4(ACSL4),and enhanced activation of hypoxia inducible factor-1α(HIF-1α),induced nitric oxide synthase(iNOS)and vascular endothelial growth factor(VEGF)in the HIF-1 signaling pathway.Treatment with MXSGD effectively reduced intracellular viral load,while reducing ROS,total iron and ferrous ion contents,repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway.Finally,based on animal experiments,it was found that MXSGD effectively alleviated pulmonary congestion,edema and inflammation in IAV-infected mice,and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.展开更多
Background:The COVID-19 has a huge negative impact on people’s health.Traditional Chinese Medicine(TCM)has a good effect on viral pneumonia.It is of great practical significance to study its pharmacology.Methods:The ...Background:The COVID-19 has a huge negative impact on people’s health.Traditional Chinese Medicine(TCM)has a good effect on viral pneumonia.It is of great practical significance to study its pharmacology.Methods:The ingredients and targets of each herb in Maxing Shigan Decoction which obtained from Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,and the related targets of COVID-19 were screened by GeneCards database based on the network pharmacology.Venn was used to analyze the intersection target between active ingredients and diseases.Cytoscape software was used to construct an active ingredient-disease target network.The protein-protein interaction network was constructed by STRING database and Cytohubba was used to screen out the key targets.Gene Ontology(GO)functional enrichment analysis and KEGG pathway analysis were performed by DAVID database.Results:In this study,a total of 134 active ingredients and 229 related targets,198 targets of COVID-19 and 48 common targets of drug-disease were chosen.Enrichment items and pathways were obtained through GO and KEGG pathway analysis.The predicted active ingredients were quercetin,kaempferol,luteolin,naringenin,glycyrol,and the key targets involved IL6,MAPK3,MAPK8,CASP3,IL10,etc.The results showed that the active ingredients of Maxing Shigan Decoction acted on multiple targets which played roles in the treatment of COVID-19 by regulating inflammation,immune system and other pathways.Conclusions:The main contribution of this paper is to use data to mine the principles of the treatment of COVID-19 from the pharmacology of these prescriptions,and the results can be provided theoretical reference for medical workers.展开更多
Objective To establish an objective method for evaluating the intrinsic characteristics between cold and hot nature of Chinese materia medica (CMM) through the different effects of Mahuang decoction (MHD) and Maxing S...Objective To establish an objective method for evaluating the intrinsic characteristics between cold and hot nature of Chinese materia medica (CMM) through the different effects of Mahuang decoction (MHD) and Maxing Shigan decoction (MSD) on animal temperature tropism. Methods The equipment with cold/hot pads was used to investigate the variety of the temperature tropism between two groups of mice treated by MHD and MSD, respectively. Meanwhile, the activities of adenosine triphosphatase (ATPase), superoxide dismutase, succinate dehydrogenase, and malondialdehyde were measured. Results After treated by MHD, the macroscopic behavioral index of remaining rate on warm pad (40 ℃ ) of mice decreased significantly (P < 0.05), suggesting the enhancement of cold tropism, meanwhile, the internal indices of ATPase activity and oxygen consuming volume increased significantly (P < 0.05), suggesting the enhancement of energy metabolism. On the other hand, the above-mentioned indices in MSD group changed on the inverse way. Conclusion The relative drug nature of MHD and MSD revealed in this study is consistent with the theoretical prognostication or definition. It indicates that the internal cold and hot nature of CMM could be reflected in ethological way on the changes of animal temperature tropism which might be internally regulated by body energy metabolism.展开更多
[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were random...[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were randomly and evenly divided into high-dose group(1.2 mL/100 g,120 g/kg),middle-dose group(96.0 g/kg),low-dose group(72.0 g/kg)and blank control group.The rats in the treatment groups were administered with corresponding doses of Maxing Erchen Zhike granules,and those in the blank control group were given with equal-amount normal saline.The administration lasted for 30 consecutive days.During the experiment,the rats'feed intake,activity,feces and other conditions and toxicity reactions were observed every day.After 24 h of the last administration,12 rats(half male and half female)were randomly selected from each group.Each of the rats was anesthetized with 10%chloral hydrate solution(0.3 mL/100 g)through intraperitoneal injection and subjected to abdominal aorta blood collection(two tubes)for hematological examination and blood biochemical examination(serum).Then,the main organs of the rats were weighed,and pathological examinations were performed.After that,the main organs were weighed and pathological examination was performed.The remaining rats in each group were discontinued and observed for 14 d.On the 15th d,they were subjected to the same treatment,and the body weight,organ coefficients,hematological indices,blood biochemical indices and pathological indices were examined.[Results]After 30 d of administration,there was no abnormality in the appearance and behavior of the animals.There was no significant difference in the daily consumption of feed among the groups,and there was no special case of weight gain.Among the blood biochemical indices,the ALB and ALT levels of each administration group were significantly different from those of the blank control group(P<0.05).The results of histopathological examination show that there was one case of interstitial pneumonia in each of the high-dose group,midd展开更多
Background:On December 8,2019,Wuhan City,Hubei Province,a new type of coronavirus disease 2019(COVID-2019)was firstly discovered,and COVID-2019 spread rapidly in China.The number of confirmed cases in various province...Background:On December 8,2019,Wuhan City,Hubei Province,a new type of coronavirus disease 2019(COVID-2019)was firstly discovered,and COVID-2019 spread rapidly in China.The number of confirmed cases in various provinces and cities rose sharply in China.In clinical treatment,Chinese medicine treatment showed significant efficacy.Since the outbreak,the National Health Commission(NHS)of China has issued seven editions of the“Pneumonitis Diagnosis and Treatment Program for COVID-2019”,at the same time,most provincial health boards and the Chinese Medicine Administration had also released information on the prevention and control scheme of COVID-2019 by Chinese medicine.The purpose of this study is to explore the compatibility rules of the main drugs in the prescription and the potential mechanism on COVID-2019 pneumonia,in order to provide reference for clinical research and new drug development of COVID-2019.Methods:This article uses the TCM inheritance assistance system and network pharmacology BATMAN-TCM online analysis system to collect and summarize the national“Pneumonitis Diagnosis and Treatment Program for COVID-2019(trial version sixth)”and formulae for adult treatment from the TCM prevention program of 23 provinces and cities.Results:We found that the most formulae for the treatment of COVID-2019 were modified on the basis of Maxing Shigan decoction and the top 5 high-frequencyn drugs are Xingren(Armeniacae semen amarum),Mahuang(Ephedrae herba),Gancao(Glycyrrhizae radix et rhizoma),Shigao(Gypsum fibrosum),and Haungqin(Radix scutellariae).High frequency traditional Chinese medicines are mainly used for relieving the symptoms,clearing away heat,eliminating dampness,resolving phlegm,relieving cough and asthma,promoting water and dampness,and tonifying deficiency.Warm medicine and bitter medicine are the most frequently used drugs in four Qi attribute and five flavor attribute,respectively.Most of drugs are belong to lung,stomach and spleen channel.Mahuang(Ephedrae herba),Xingren(Armeniacae semen amarum)展开更多
COVID-19 is caused by novel coronavirus(2019-nCoV),which has the characteristics of strong infectivity,rapid onset and rapid spread.It is popular in China and other parts of the world,and there are no special drugs at...COVID-19 is caused by novel coronavirus(2019-nCoV),which has the characteristics of strong infectivity,rapid onset and rapid spread.It is popular in China and other parts of the world,and there are no special drugs at present.This disease belongs to the category of plague in traditional Chinese medicine.Combined with the theory of triple energizer transmission in Yang Lishan's"Identification of Warm Disease",the confirmed case in our hospital was analyzed,and it was found that pathogenic qi entered from nose and mouth,injected into middle energizer,and then distributed in upper and lower energizer.The pathogenic qi is mainly diffused in the middle and upper energizer.Modified Maxing Ganshi decoction has a good effect.展开更多
基金supported by the National Natural Science Foundation of China(No.81973670)the Natural Science Foundation of Hunan Province(No.2020J5418)Hunan Provincial Open Fund of the Key Laboratory of the Pathogen Biology of Integrated Traditional Chinese and Western Medicine(No.2022-KFJJ02).
文摘Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide.Influenza A virus(IAV)has been found to activate multiple programmed cell death pathways,including ferroptosis.Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation,leading to cell death.However,little is known about how influenza viruses induce ferroptosis in the host cells.In this study,based on network pharmacology,we predicted the mechanism of action of Maxing Shigan decoction(MXSGD)in IAV-induced ferroptosis,and found that this process was related to biological processes,cellular components,molecular function and multiple signaling pathways,where the hypoxia inducible factor-1(HIF-1)signaling pathway plays a significant role.Subsequently,we constructed the mouse lung epithelial(MLE-12)cell model by IAV-infected in vitro cell experiments,and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage,increased reactive oxygen species(ROS)release,increased total iron and iron ion contents,decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4(GPX4),increased expression of acyl-CoA synthetase long chain family member 4(ACSL4),and enhanced activation of hypoxia inducible factor-1α(HIF-1α),induced nitric oxide synthase(iNOS)and vascular endothelial growth factor(VEGF)in the HIF-1 signaling pathway.Treatment with MXSGD effectively reduced intracellular viral load,while reducing ROS,total iron and ferrous ion contents,repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway.Finally,based on animal experiments,it was found that MXSGD effectively alleviated pulmonary congestion,edema and inflammation in IAV-infected mice,and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
基金the National Natural Science Foundation of China(Nos.62072157 and 61802116)the Natural Science Foundation of Henan province(202300410102)+1 种基金the Doctoral program of Henan Institute of Technology(KQ2002)the Science and Technology Research Key Project of Henan Province(No.192102210113).
文摘Background:The COVID-19 has a huge negative impact on people’s health.Traditional Chinese Medicine(TCM)has a good effect on viral pneumonia.It is of great practical significance to study its pharmacology.Methods:The ingredients and targets of each herb in Maxing Shigan Decoction which obtained from Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,and the related targets of COVID-19 were screened by GeneCards database based on the network pharmacology.Venn was used to analyze the intersection target between active ingredients and diseases.Cytoscape software was used to construct an active ingredient-disease target network.The protein-protein interaction network was constructed by STRING database and Cytohubba was used to screen out the key targets.Gene Ontology(GO)functional enrichment analysis and KEGG pathway analysis were performed by DAVID database.Results:In this study,a total of 134 active ingredients and 229 related targets,198 targets of COVID-19 and 48 common targets of drug-disease were chosen.Enrichment items and pathways were obtained through GO and KEGG pathway analysis.The predicted active ingredients were quercetin,kaempferol,luteolin,naringenin,glycyrol,and the key targets involved IL6,MAPK3,MAPK8,CASP3,IL10,etc.The results showed that the active ingredients of Maxing Shigan Decoction acted on multiple targets which played roles in the treatment of COVID-19 by regulating inflammation,immune system and other pathways.Conclusions:The main contribution of this paper is to use data to mine the principles of the treatment of COVID-19 from the pharmacology of these prescriptions,and the results can be provided theoretical reference for medical workers.
基金National Basic Research Program of China ("973" Program) (2007CB5126072006CB504703)National Science Fund for Distinguished Young Scholars (30625042)
文摘Objective To establish an objective method for evaluating the intrinsic characteristics between cold and hot nature of Chinese materia medica (CMM) through the different effects of Mahuang decoction (MHD) and Maxing Shigan decoction (MSD) on animal temperature tropism. Methods The equipment with cold/hot pads was used to investigate the variety of the temperature tropism between two groups of mice treated by MHD and MSD, respectively. Meanwhile, the activities of adenosine triphosphatase (ATPase), superoxide dismutase, succinate dehydrogenase, and malondialdehyde were measured. Results After treated by MHD, the macroscopic behavioral index of remaining rate on warm pad (40 ℃ ) of mice decreased significantly (P < 0.05), suggesting the enhancement of cold tropism, meanwhile, the internal indices of ATPase activity and oxygen consuming volume increased significantly (P < 0.05), suggesting the enhancement of energy metabolism. On the other hand, the above-mentioned indices in MSD group changed on the inverse way. Conclusion The relative drug nature of MHD and MSD revealed in this study is consistent with the theoretical prognostication or definition. It indicates that the internal cold and hot nature of CMM could be reflected in ethological way on the changes of animal temperature tropism which might be internally regulated by body energy metabolism.
基金Scientific Research Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine(2017ZJ006)Key Research and Development Project of Department of Science and Technology of Guangxi Zhuang Autonomous Region(AB19110003).
文摘[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were randomly and evenly divided into high-dose group(1.2 mL/100 g,120 g/kg),middle-dose group(96.0 g/kg),low-dose group(72.0 g/kg)and blank control group.The rats in the treatment groups were administered with corresponding doses of Maxing Erchen Zhike granules,and those in the blank control group were given with equal-amount normal saline.The administration lasted for 30 consecutive days.During the experiment,the rats'feed intake,activity,feces and other conditions and toxicity reactions were observed every day.After 24 h of the last administration,12 rats(half male and half female)were randomly selected from each group.Each of the rats was anesthetized with 10%chloral hydrate solution(0.3 mL/100 g)through intraperitoneal injection and subjected to abdominal aorta blood collection(two tubes)for hematological examination and blood biochemical examination(serum).Then,the main organs of the rats were weighed,and pathological examinations were performed.After that,the main organs were weighed and pathological examination was performed.The remaining rats in each group were discontinued and observed for 14 d.On the 15th d,they were subjected to the same treatment,and the body weight,organ coefficients,hematological indices,blood biochemical indices and pathological indices were examined.[Results]After 30 d of administration,there was no abnormality in the appearance and behavior of the animals.There was no significant difference in the daily consumption of feed among the groups,and there was no special case of weight gain.Among the blood biochemical indices,the ALB and ALT levels of each administration group were significantly different from those of the blank control group(P<0.05).The results of histopathological examination show that there was one case of interstitial pneumonia in each of the high-dose group,midd
文摘Background:On December 8,2019,Wuhan City,Hubei Province,a new type of coronavirus disease 2019(COVID-2019)was firstly discovered,and COVID-2019 spread rapidly in China.The number of confirmed cases in various provinces and cities rose sharply in China.In clinical treatment,Chinese medicine treatment showed significant efficacy.Since the outbreak,the National Health Commission(NHS)of China has issued seven editions of the“Pneumonitis Diagnosis and Treatment Program for COVID-2019”,at the same time,most provincial health boards and the Chinese Medicine Administration had also released information on the prevention and control scheme of COVID-2019 by Chinese medicine.The purpose of this study is to explore the compatibility rules of the main drugs in the prescription and the potential mechanism on COVID-2019 pneumonia,in order to provide reference for clinical research and new drug development of COVID-2019.Methods:This article uses the TCM inheritance assistance system and network pharmacology BATMAN-TCM online analysis system to collect and summarize the national“Pneumonitis Diagnosis and Treatment Program for COVID-2019(trial version sixth)”and formulae for adult treatment from the TCM prevention program of 23 provinces and cities.Results:We found that the most formulae for the treatment of COVID-2019 were modified on the basis of Maxing Shigan decoction and the top 5 high-frequencyn drugs are Xingren(Armeniacae semen amarum),Mahuang(Ephedrae herba),Gancao(Glycyrrhizae radix et rhizoma),Shigao(Gypsum fibrosum),and Haungqin(Radix scutellariae).High frequency traditional Chinese medicines are mainly used for relieving the symptoms,clearing away heat,eliminating dampness,resolving phlegm,relieving cough and asthma,promoting water and dampness,and tonifying deficiency.Warm medicine and bitter medicine are the most frequently used drugs in four Qi attribute and five flavor attribute,respectively.Most of drugs are belong to lung,stomach and spleen channel.Mahuang(Ephedrae herba),Xingren(Armeniacae semen amarum)
基金The Science and Technology Program of Guangdong,China(nos.SDZX2020024SDZX2020055).+6 种基金Project of Chinese Medicine Administration of Guangdong Province,China(nos.2020ZYYJ182020139220201388Guangdong Traditional Chinese Medicine[2019]No.1)Science and Technology Program of Yangjiang,China(nos.201839201950)。
文摘COVID-19 is caused by novel coronavirus(2019-nCoV),which has the characteristics of strong infectivity,rapid onset and rapid spread.It is popular in China and other parts of the world,and there are no special drugs at present.This disease belongs to the category of plague in traditional Chinese medicine.Combined with the theory of triple energizer transmission in Yang Lishan's"Identification of Warm Disease",the confirmed case in our hospital was analyzed,and it was found that pathogenic qi entered from nose and mouth,injected into middle energizer,and then distributed in upper and lower energizer.The pathogenic qi is mainly diffused in the middle and upper energizer.Modified Maxing Ganshi decoction has a good effect.
