Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*