By combining network pharmacology and in vitro experiments, this study sought to understand both the impact and molecular mechanisms of Xuebijing Injection in treating sepsis-induced acute respiratory distress syndrome (ARDS). The TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) was used to screen and anticipate the targets of the active components in Xuebijing Injection. Using GeneCards, DisGeNet, OMIM, and TTD databases, the research team identified sepsis-associated ARDS targets. The main active components of Xuebijing Injection, along with sepsis-associated ARDS targets, were mapped using the Weishengxin platform. A Venn diagram was subsequently built to identify any overlapping targets. The 'drug-active components-common targets-disease' network architecture was established using the Cytoscape 39.1 platform. neurodegeneration biomarkers The protein-protein interaction (PPI) network, originating from common targets incorporated into the STRING database, was imported into Cytoscape 39.1 for visualization. DAVID 68 was utilized to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the shared targets, subsequently visualized using the Weishe-ngxin platform. The KEGG network was created by importing the top 20 KEGG signaling pathways into Cytoscape version 39.1. predictive genetic testing Finally, molecular docking, in conjunction with in vitro cell experiments, was utilized to confirm the predictions. Of the components and targets analyzed, a total of 115 active components and 217 targets were found in Xuebijing Injection. Meanwhile, 360 targets were associated with sepsis-associated ARDS. Remarkably, 63 of these targets were present in both Xuebijing Injection and the disease. Targets of the investigation included interleukin-1 beta (IL-1), IL-6, albumin (ALB), serine/threonine-protein kinase (AKT1), and vascular endothelial growth factor A (VEGFA). The GO term annotation encompasses a total of 453 terms, specifically 361 under biological processes, 33 under cellular components, and 59 under molecular functions. Lipopolysaccharide's cellular impact, along with apoptotic inhibition, lipopolysaccharide signaling pathways, RNA polymerase promoter transcription enhancement, hypoxic reaction, and inflammatory response, were the central themes. The KEGG enrichment analysis uncovered 85 distinct pathways. Upon the exclusion of diseases and general pathways, a subsequent analysis focused on hypoxia-inducible factor-1 (HIF-1), tumor necrosis factor (TNF), nuclear factor-kappa B (NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways. Molecular docking studies confirmed that the significant active components of Xuebijing Injection demonstrated effective binding with their key therapeutic targets. In vitro experiments using Xuebijing Injection showed a decrease in the activity of HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, preventing cell apoptosis and reactive oxygen species production, and decreasing the expression of TNF-α, IL-1β, and IL-6 in cells. In essence, Xuebijing Injection's efficacy in treating sepsis-associated ARDS derives from its capacity to control apoptosis, manage inflammation, and mitigate oxidative stress through modulation of HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways.
To rapidly determine the composition of Liangxue Tuizi Mixture, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and the UNIFI system were employed. Data on the targets of the active components and Henoch-Schönlein purpura (HSP) were sourced from SwissTargetPrediction, Online Mendelian Inheritance in Man (OMIM), and GeneCards. Two networks were created: a 'component-target-disease' network and a protein-protein interaction (PPI) network. By way of Omishare's analysis, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on the targets. Molecular docking confirmed the interactions between the possible active ingredients and the central targets. Moreover, rats were randomly assigned to a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups, respectively. A 'component-target-differential metabolite' network was constructed from the results of non-targeted metabolomics screening of serum for differential metabolites, followed by the analysis of possible metabolic pathways. Liangxue Tuizi Mixture contained a total of 45 identified components, which were predicted to potentially target 145 HSP treatment pathways. The analysis revealed resistance to epidermal growth factor receptor tyrosine kinase inhibitors, the phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) pathway, and the engagement of T cell receptors as being among the most enriched signaling pathways. Key target proteins demonstrated strong binding affinity with active components of Liangxue Tuizi Mixture, as evidenced by molecular docking simulations. Analysis of serum samples identified 13 differential metabolites, and 27 of these had matching targets in active compounds. The progression of HSP correlated with a disruption of metabolic processes in both glycerophospholipids and sphingolipids. Liangxue Tuizi Mixture's components, as indicated by the results, primarily address HSP through the modulation of inflammation and immunity, thus establishing a scientific rationale for its clinical application.
Over the past few years, a growing number of reports detail adverse effects stemming from traditional Chinese medicine, particularly those traditionally categorized as 'harmless' TCMs, like Dictamni Cortex. Scholars are concerned about this development. This study on four-week-old mice investigates the metabolomic basis for sex-dependent differences in liver injury induced by dictamnine treatment. The results explicitly showed that dictamnine led to a considerable rise in serum biochemical indicators of liver function and organ coefficients (P<0.05), with female mice displaying hepatic alveolar steatosis as a prominent feature. selleck chemicals Although other alterations were absent, no histopathological changes materialized in the male mice. Subsequently, untargeted metabolomics and multivariate statistical analyses distinguished 48 differential metabolites, including tryptophan, corticosterone, and indole, which are linked to disparities in liver injury between male and female subjects. The ROC curve demonstrated 14 metabolites having a significant correlation with the variation. Ultimately, pathway enrichment analysis suggested that disruptions in metabolic pathways, including tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis (specifically encompassing linoleic acid and arachidonic acid metabolism), could underlie the observed divergence. The sex-dependent response to dictamnine-mediated liver damage is pronounced, likely attributable to variations in tryptophan metabolism, steroid hormone production, and ferroptosis.
Utilizing the O-GlcNAc transferase (OGT)-PTEN-induced putative kinase 1 (PINK1) pathway, the study investigated the mechanism by which 34-dihydroxybenzaldehyde (DBD) affects mitochondrial quality control. The rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The SD rats were randomly divided into four cohorts: a sham group, an MCAO/R model group, and two DBD treatment groups (5 mg/kg and 10 mg/kg, respectively). Seven days after intra-gastric administration, rats (excluding the sham group) experienced MCAO/R induction using a surgical suture method. Evaluations of both neurological function and the percentage of the cerebral infarct area were performed 24 hours after the reperfusion procedure. The pathological damage suffered by cerebral neurons was characterized using both hematoxylin and eosin (H&E) staining and Nissl staining. Immunofluorescence staining was used to ascertain the co-localization of light chain-3 (LC3), sequestosome-1 (SQSTM1/P62), and Beclin1, after the mitochondria's ultrastructure had been observed via electron microscopy. Mitochondrial autophagy, triggered by the OGT-PINK1 pathway, is reported as a crucial mechanism for maintaining mitochondrial quality. Western blot analysis served to detect the expression of OGT, mitophagy-related proteins PINK1 and Parkin, as well as mitochondrial dynamic proteins Drp1 and Opa1. The MCAO/R group exhibited neurological deficits, a substantial cerebral infarct area (P<0.001), and structural damage to neurons, along with a reduction in Nissl bodies, mitochondrial swelling, loss of cristae, a decrease in LC3 and Beclin1-positive cells, an increase in P62-positive cells (P<0.001), inhibited OGT, PINK1, and Parkin expression, enhanced Drp1 expression, and diminished Opa1 expression when compared to the sham group (P<0.001). Despite prior deficiencies, DBD demonstrably enhanced behavioral performance and mitochondrial health in MCAO/R rats, as indicated by improved neuronal and mitochondrial morphology, and an increase in Nissl bodies. Deeper analysis revealed that DBD treatment led to an increase in cells showcasing LC3 and Beclin1, coupled with a decrease in cells expressing P62 (P<0.001). Moreover, DBD stimulated the expression of OGT, PINK1, Parkin, and Opa1, and curbed the expression of Drp1, thus promoting mitophagy (P<0.005, P<0.001). In the end, DBD's action on the mitochondrial network is to catalyze PINK1/Parkin-mediated brain mitophagy by means of the OGT-PINK1 pathway, ensuring a healthy state. Promoting nerve cell survival and improving cerebral ischemia/reperfusion injury may be achieved through a mitochondrial therapeutic mechanism.
UHPLC-IM-Q-TOF-MS data facilitated the development of a strategy encompassing collision cross section (CCS) prediction and quantitative structure-retention relationship (QSRR) modelling, applied to determine quinoline and isoquinoline alkaloids in Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex.