Tribuloside: Mechanisms and Efficacy in Treating Acute Lung Injury Revealed by Network Pharmacology and Experimental Validation.

Background: Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo. Objective: This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation. Methods: We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the "drug or disease-target" network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside's therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1ß in the lungs through many pathways and targets. Conclusion: This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation.

Research on acute lung injury inflammatory network.

Acute lung injury (ALI) is a systemic inflammatory response syndrome in the lungs, with a high incidence and fatality rate of 30 - 40%. Despite the abundance of research on the pathogenesis of lung injury and the great progress that has been achieved, the various number of cells, cytokines and inflammatory response pathways involved in the pathogenesis of ALI and their complex relationships - which together constitute the cell network and inflammatory factor network of ALI inflammatory response - demand more attention. This study reviews the formation of this network in the pathogenesis of ALI.

Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin-induced pulmonary fibrosis in mice.

The purpose of this study was to explore the protective effect and potential mechanism of berberine on bleomycin (BLM)-induced fibrosis after lung injury in conjunction with network pharmacology. Berberine and pulmonary fibrosis prediction targets were collected for Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and so forth. A single intranasal dose of BLM (2.5 mg/kg) was administered to establish a model of fibrosis after lung injury, and berberine (50 mg/kg) was administered intraperitoneally daily for treatment. Network pharmacology results suggested that the mitogen-activated protein kinase (MAPK) signalling pathway may be a potential mechanism of berberine in delaying pulmonary fibrosis. The results of animal experiments showed that compared with the BLM group, after 14 days of berberine treatment, lung inflammatory cell aggregation was reduced and the expression levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-6 were down-regulated in mice (p < 0.05); after 42 days of berberine treatment, the expression levels of transforming growth factor (TGF)-ß1, platelet-derived growth factor-AB (PDGF-AB), hydroxyproline (HYP) and α-smooth muscle actin (α-SMA) were significantly down-regulated (p < 0.05), and the expression levels of total p38 MAPKα and p38 MAPKα (pT180/Y182) were down-regulated also (p < 0.05), inhibited collagen production and deposition, and increased the survival rate of mice to 70%. In conclusion, berberine attenuated inflammation mice, inhibited collagen production and showed some anti-pulmonary fibrosis potential in the MAPK signalling pathway.

The study of metabolism and metabolomics in a mouse model of silica pulmonary fibrosis based on UHPLC-QE-MS.

The small diameter crystalline silica is inhaled into the lung and cannot be cleared. As a result, the patient suffers from silicosis, a lung disease for which there is no effective treatment except lung transplantation. The aim of this study is to reveal the histological, cytological and metabolic characteristics of mice with pulmonary fibrosis induced by different doses of silica, and to provide an ideal animal model for drug development and disease research of pulmonary fibrosis. The experimental mice were divided into five groups. The mice were sacrificed 42 d later by nasal inhalation of normal saline and suspension containing silica 1 mg, 2 mg, 4 mg and 8 mg. Lung specimens and bronchoalveolar lavage fluid (BALF) were collected for histological and cytological examination. Carotid blood was collected and centrifuged to obtain serum for UHPLC-QE-MS non-target metabolomics detection. Compared with the normal control group, except 1 mg silica group, the other dosage groups showed different degree of disease characteristics. Metabolomics analysis showed that arginine and proline metabolism, pentose phosphate pathway, histidine metabolism, cysteine and methionine metabolism, ascorbic acid and aldoglucose metabolism were important metabolic pathways. This study reveals the histological, cytological and metabolic features of four-dose-gradient silica-induced pulmonary fibrosis mouse models.

The function of non-coding RNAs in idiopathic pulmonary fibrosis.

Non-coding ribonucleic acids (ncRNAs) are a diverse group of RNA molecules that are mostly not translated into proteins after transcription, including long non-coding RNAs (lncRNAs) with longer than 200 nucleotides non-coding transcripts and microRNAs (miRNAs) which are only 18-22 nucleotides. As families of evolutionarily conserved ncRNAs, lncRNAs activate and repress genes via a variety of mechanisms at both transcriptional and translational levels, whereas miRNAs regulate protein-coding gene expression mainly through mRNA silencing. ncRNAs are widely involved in biological functions, such as proliferation, differentiation, migration, angiogenesis, and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. The etiology of IPF is still unclear. Increasing evidence shows the close correlations between the development of IPF and aberrant expressions of ncRNAs than thought previously. In this study, we provide an overview of ncRNAs participated in pathobiology of IPF, seeking the early diagnosis biomarker and aiming for potential therapeutic applications for IPF.

MicroRNA-150 deficiency accelerates intimal hyperplasia by acting as a novel regulator of macrophage polarization.

BACKGROUND: The infiltration and activation of macrophages play key roles in arterial restenosis, providing a promising strategy for the treatment of restenosis caused by intimal hyperplasia. Although miR-150 has been implicated in cardiovascular diseases, the individual effect of miR-150 on intimal hyperplasia remains unclear. METHODS AND RESULTS: We observed that the expression of miR-150 was robustly reduced in proinflammatory M1 macrophages and reversely induced in resolving M2 macrophages. An in vitro experiment demonstrated that miR-150 deficiency promoted extensive upregulation of the expression of M1 markers but attenuated the expression of M2 macrophage markers. MiR-150 enhanced the proliferation and migration of vascular smooth muscle cells (VSMCs) when co-cultured with conditioned medium from polarized macrophages upon LPS or IL-4 stimulation. Mechanistically, the bioinformatics analysis and luciferase assay results showed that miR-150 directly targeted STAT1 and STAT1 was required for the effect of miR-150 knockout on macrophage polarization. More importantly, we showed that knockout of miR-150 accelerated neointima formation, accompanied by the activation of M1 macrophages and the inactivation of M2 macrophages. Furthermore, miR-150 deficiency in marrow-derived cell accelerated neointima formation. CONCLUSION: Our research demonstrated that miR-150 deficiency promoted intimal hyperplasia with high ratios of M1 to M2 macrophages and subsequently increased VSMCs proliferation and migration, which were partially mediated by directly targeting to STAT1. Collectively, these results suggested that miR-150 may act as a novel therapeutic target for arterial restenosis.

A Comparison Study of Ag Composites Prepared by Spark Plasma Sintering and Hot Pressing with Silver-Coated CNTs as the Reinforcements.

In this study, carbon nanotube-reinforced silver composites (CNT/Ag) were prepared by the powder metallurgy process via spark plasma sintering (SPS) and hot pressing sintering (HP) with composite powders through an improved electroless plating method assisted by ultrasonic spray atomization. The dispersion of CNTs was effectively improved by ultrasonic spray atomization, and uniform silver layers were deposited on the surface of CNTs by electroless deposition. The property testing results showed significant improvements of the electrical conductivity, hardness, and tensile strength in the samples prepared by SPS, as compared to their HP sintered counterparts. When the volume fraction of CNTs reached 2.5%, the tensile strength reached a maximum value of 221 MPa, which was more than twice that of the pure silver samples. The structural analysis indicated different degrees of CNT agglomeration and matrix mean grain sizes in the composites prepared by SPS and HP, which are responsible for the differences in properties.