Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related t...Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.展开更多
Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat ...Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat model of acute pneumonia was developed by treating rats with lipopolysaccharide(LPS)through a non-exposed tracheal drip.The pharmacological effects of HQSGD were evaluated via histopathological analysis of rat lung tissues,histological scoring of lung injury,assessment of lung index,serum inflammatory factors,oxidative stress levels,western blotting,and qRT-PCR.The active compounds of HQSGD were detected utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).NP and transcriptomic analysis were integrated to determine signaling pathways implicated in the pharmacological activity of HQSGD.The expression levels of mRNA and protein for factors implicated in these pathways were evaluated in rat lung tissues via qRT-PCR and western blotting,respectively.Results:HQSGD alleviated acute pneumonia in rats by reducing the lung index and the levels of TNF-α,IL-1β,CRP,and MDA while increasing the levels of SOD.The UPLC-MS/MS and NP techniques facilitated the identification of 28 bioactive constituents present in HQSGD.The principal 20 KEGG pathways were identified by intersecting the targets of HQSGD with pneumonia-related targets.These pathways were screened by comparing the transcriptomic data of the blank and model cohorts and those of the model and drug administration cohorts.GO and KEGG analyses indicated that the PI3K/AKT/NF-κB pathway was a potentially effective target of HQSGD.Conclusion:This investigation revealed the overall multi-component,multi-target,and multi-pathway interactions of HQSGD in the treatment of acute pneumonia.展开更多
基金supported by the National Natural Science Foundation of China(grant No.81973592)the Shaanxi Provincial Administration of Traditional Chinese Medicine Project(grant No.2021-GJ-JC004).
文摘Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.
基金the"Qin Medicine"Quality Evaluation and Resource Development Discipline Innovation Team Project of Shaanxi University of Traditional Chinese Medicine(2019-QN01)Shaanxi University of Traditional Chinese Medicine School of Pharmacy/Shaanxi Engineering Research Centre for the Application and Development of Qinling Herbal Medicine,"Qin Medicine"Research and Development Key Laboratory(2019-QYPT-002)+2 种基金Shaanxi Provincial Administration of Traditional Chinese Medicine Province,Research and Development Key Laboratory(2019-QYPT-002)Shaanxi Provincial Administration of Traditional Chinese Medicine Province Chinese medicine province-wide earmarked special project:"Qin medicine planting and breeding guide research"(2021-QYZL-02)Shaanxi Provincial Science and Technology Department project:Chinese medicine Scutellaria baicalensis germplasm selection,seedling breeding and planting key technology research(2016KTTSSF01-01-01)and other projects.
文摘Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat model of acute pneumonia was developed by treating rats with lipopolysaccharide(LPS)through a non-exposed tracheal drip.The pharmacological effects of HQSGD were evaluated via histopathological analysis of rat lung tissues,histological scoring of lung injury,assessment of lung index,serum inflammatory factors,oxidative stress levels,western blotting,and qRT-PCR.The active compounds of HQSGD were detected utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).NP and transcriptomic analysis were integrated to determine signaling pathways implicated in the pharmacological activity of HQSGD.The expression levels of mRNA and protein for factors implicated in these pathways were evaluated in rat lung tissues via qRT-PCR and western blotting,respectively.Results:HQSGD alleviated acute pneumonia in rats by reducing the lung index and the levels of TNF-α,IL-1β,CRP,and MDA while increasing the levels of SOD.The UPLC-MS/MS and NP techniques facilitated the identification of 28 bioactive constituents present in HQSGD.The principal 20 KEGG pathways were identified by intersecting the targets of HQSGD with pneumonia-related targets.These pathways were screened by comparing the transcriptomic data of the blank and model cohorts and those of the model and drug administration cohorts.GO and KEGG analyses indicated that the PI3K/AKT/NF-κB pathway was a potentially effective target of HQSGD.Conclusion:This investigation revealed the overall multi-component,multi-target,and multi-pathway interactions of HQSGD in the treatment of acute pneumonia.
