Effective-compounds of Jinshui Huanxian formula ameliorates fibroblast activation in pulmonary fibrosis by inhibiting the activation of mTOR signaling

Li, Jiansheng; Li, Kangchen; Tian, Yan-Ge; Zhao, Peng; Liu, Xuefang; Li, Minyan; Bai, Yunping

doi:10.1016/j.phymed.2022.154604

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…A pulmonary fibrosis cell model was established through HFL fibroblast cells induced by TGF-β1 (5 ng/mL) to activate fibroblasts, while the control group was not treated. The changes in HFL cells induced by TGF-β1 are similar to the pathological changes in human pulmonary fibrotic disease, suggesting that a TGF-β1-induced fibroblast activation model has been successfully established, which has also been used as a model for interstitial pneumonia in other studies [ 34 , 35 ]. After 6 h of induction, two groups of cells were harvested for quantitative polymerase chain reaction (qPCR) experiments.…”

Section: Methodsmentioning

confidence: 99%

Integrated bioinformatics analysis for the identification of idiopathic pulmonary fibrosis–related genes and potential therapeutic drugs

Zhang,

Guan,

Tian

et al. 2023

BMC Pulm Med

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Objective The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. We sought to identify IPF-related genes that may participate in the pathogenesis and predict potential targeted traditional Chinese medicines (TCMs). Methods Using IPF gene-expression data, Wilcoxon rank-sum tests were performed to identify differentially expressed genes (DEGs). Protein–protein interaction (PPI) networks, hub genes, and competitive endogenous RNA (ceRNA) networks were constructed or identified by Cytoscape. Quantitative polymerase chain reaction (qPCR) experiments in TGF-β1-induced human fetal lung (HFL) fibroblast cells and a pulmonary fibrosis mouse model verified gene reliability. The SymMap database predicted potential TCMs targeting IPF. The reliability of TCMs was verified in TGF-β1-induced MRC-5 cells. Materials Multiple gene-expression profile data of normal lung and IPF tissues were downloaded from the Gene Expression Omnibus database. HFL fibroblast cells and MRC-5 cells were purchased from Wuhan Procell Life Science and Technology Co., Ltd. (Wuhan, China). C57BL/12 mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Results In datasets GSE134692 and GSE15197, DEGs were identified using Wilcoxon rank-sum tests (both p < 0.05). Among them, 1885 DEGs were commonly identified, and 87% (1640 genes) had identical dysregulation directions (binomial test, p < 1.00E-16). A PPI network with 1623 nodes and 8159 edges was constructed, and 18 hub genes were identified using the Analyze Network plugin in Cytoscape. Of 18 genes, CAV1, PECAM1, BMP4, VEGFA, FYN, SPP1, and COL1A1 were further validated in the GeneCards database and independent dataset GSE24206. ceRNA networks of VEGFA, SPP1, and COL1A1 were constructed. The genes were verified by qPCR in samples of TGF-β1-induced HFL fibroblast cells and pulmonary fibrosis mice. Finally, Sea Buckthorn and Gnaphalium Affine were predicted as potential TCMs for IPF. The TCMs were verified by qPCR in TGF-β1-induced MRC-5 cells. Conclusion This analysis strategy may be useful for elucidating novel mechanisms underlying IPF at the transcriptome level. The identified hub genes may play key roles in IPF pathogenesis and therapy.

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Section: Methodsmentioning

confidence: 99%

Integrated bioinformatics analysis for the identification of idiopathic pulmonary fibrosis–related genes and potential therapeutic drugs

Zhang,

Guan,

Tian

et al. 2023

BMC Pulm Med

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“…There has been no major clinical breakthrough in treatments in Western medicine, in which it is currently treated mainly by anti-inflammatory, immunosuppressives, and lung transplantation, but the disadvantages are limited efficacy, high cost, and obvious side effects [ 7 ]. JHGs have shown clear efficacy in the treatment of pulmonary fibrosis [ 8 ]. They consists of 10 Chinese medicines, including Epimedium brevicornu Maxim, Panax ginseng C.A.Mey., Ophiopogon japonicus (Thunb.)…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…JHGs have shown clear efficacy in the treatment of pulmonary fibrosis [8]. They consists of 10 Chinese medicines, including Epimedium brevicornu Maxim, Panax ginseng C.A.Mey., Ophiopogon japonicus (Thunb.)…”

Section: Introductionmentioning

confidence: 99%

“…The clinical treatment evaluated the efficacy and long-term effects of JHGs in the treatment of PF from several indexes, with the effects of improving lung function, inhibiting inflammation, reducing lung tissue damage, and improving the degree of pulmonary fibrosis [9,10]. The efficacy and safety research of CM including JHG treatment for IPF to ensure the adverse reactions of JHGs were few and well-tolerated [8,11]. Furthermore, pharmacological studies found that JHGs had significant therapeutic and long-term effects on pulmonary fibrosis in rats by repairing the balance of Nrf 2 -NOX 4 and decreasing the oxidative response [12].…”

Section: Introductionmentioning

confidence: 99%

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A Pharmacokinetic Study of Sixteen Major Bioactive Components of Jinshui-Huanxian Granules in Pulmonary Fibrosis Model and Control Rats Using Orbitrap Fusion Mass Spectrometry

Zhang,

Wan,

Sun

et al. 2023

Molecules

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Jinshui-Huanxian granules (JHGs), a Chinese herbal compound prescription, have shown a therapeutic effect in reducing lung tissue damage, improving the degree of pulmonary fibrosis, replenishing lungs and kidneys, relieving cough and asthma, reducing phlegm, and activating blood circulation. However, these active compounds’ pharmacokinetics and metabolic processes were unclear. This study aimed to compare the pharmacokinetics, reveal the metabolic dynamic changes, and obtain the basic pharmacokinetic parameters of 16 main bioactive compounds after intragastric administration of JHGs in control and pulmonary fibrosis (PF) model rats by using Orbitrap Fusion MS. After administration of JHGs, the rat plasma was collected at different times. Pretreating the plasma sample with methanol and internal standard (IS) solution carbamazepine (CBZ), and it was then applied to a C18 column by setting gradient elution with a mobile phase consisting of methanol 0.1% formic acid aqueous solution. Detection was performed on an electrospray ionization source (ESI), and the scanning mode was SIM. Pharmacokinetic parameters were analyzed according to the different analytes’ concentrations in plasma. The matrix effect was within the range of 79.01–110.90%, the extraction recovery rate was 80.37–102.72%, the intra-day and inter-day precision relative standard deviation (RSD) was less than 7.76%, and the stability was good, which met the requirements of biological sample testing. The method was validated (r ≥ 0.9955) and applied to compare the pharmacokinetic profiles of the control group and PF model group after intragastric administration of the JHGs. The 16 analytes exhibited different pharmacokinetic behaviors in vivo. In the pathological state of the PF model, most of the components were more favorable for metabolism and absorption, and it was more meaningful to study the pharmacokinetics. Above all, this study provided an essential reference for exploring the mechanism of action of JHGs and guided clinical medication as well.

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Qingkailing granule alleviates pulmonary fibrosis by inhibiting PI3K/AKT and SRC/STAT3 signaling pathways

Li,

Xin,

Zhou

et al. 2024

Bioorganic Chemistry

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Effective-compounds of Jinshui Huanxian formula ameliorates fibroblast activation in pulmonary fibrosis by inhibiting the activation of mTOR signaling

Cited by 8 publications

References 38 publications

Integrated bioinformatics analysis for the identification of idiopathic pulmonary fibrosis–related genes and potential therapeutic drugs

Integrated bioinformatics analysis for the identification of idiopathic pulmonary fibrosis–related genes and potential therapeutic drugs

A Pharmacokinetic Study of Sixteen Major Bioactive Components of Jinshui-Huanxian Granules in Pulmonary Fibrosis Model and Control Rats Using Orbitrap Fusion Mass Spectrometry

Qingkailing granule alleviates pulmonary fibrosis by inhibiting PI3K/AKT and SRC/STAT3 signaling pathways

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