Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
The WSC proteins produced by Penicillium expansum play a crucial role in causing blue mold on pears.To analyze the role of the WSC1 gene in the pathogenic process of this fungal pathogen,we conducted transcriptomic an...The WSC proteins produced by Penicillium expansum play a crucial role in causing blue mold on pears.To analyze the role of the WSC1 gene in the pathogenic process of this fungal pathogen,we conducted transcriptomic analysis of a WSC1 knockout(ΔWSC1)strain.The knockout of WSC1 significantly altered the gene expression profile in P.expansum,particularly for genes involved in cell wall integrity,signaling,stress response,and toxin production.The differential expression of these genes might make theΔWSC1 strain more vulnerable to environmental stress,while reducing the toxin production capacity,ultimately leading to a decrease in the pathogenicity.The transcriptomic analysis revealed that the expression of genes related to stress response signals,defense mechanisms and oxidative stress management changed when pear fruits were infected with theΔWSC1 strain.These changes may trigger a cascade of responses in pear fruits.In addition,compared with those infected with the wild-type strain,pear fruits infected with theΔWSC1 strain exhibited up-regulated expression of genes related to defense and oxidative stress.This study clarifies how the WSC1 gene influences P.expansum’s ability to infect pear fruits and how pear fruits respond to the infection.展开更多
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
文摘Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
文摘The WSC proteins produced by Penicillium expansum play a crucial role in causing blue mold on pears.To analyze the role of the WSC1 gene in the pathogenic process of this fungal pathogen,we conducted transcriptomic analysis of a WSC1 knockout(ΔWSC1)strain.The knockout of WSC1 significantly altered the gene expression profile in P.expansum,particularly for genes involved in cell wall integrity,signaling,stress response,and toxin production.The differential expression of these genes might make theΔWSC1 strain more vulnerable to environmental stress,while reducing the toxin production capacity,ultimately leading to a decrease in the pathogenicity.The transcriptomic analysis revealed that the expression of genes related to stress response signals,defense mechanisms and oxidative stress management changed when pear fruits were infected with theΔWSC1 strain.These changes may trigger a cascade of responses in pear fruits.In addition,compared with those infected with the wild-type strain,pear fruits infected with theΔWSC1 strain exhibited up-regulated expression of genes related to defense and oxidative stress.This study clarifies how the WSC1 gene influences P.expansum’s ability to infect pear fruits and how pear fruits respond to the infection.
