From the databases TCMSP, TCMID, PubChem, PharmMapper, GeneCards, and OMIM, collect disease-related targets and compounds, and identify genes shared between them. An analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was carried out using R. By injecting lipopolysaccharide (LPS) intracerebroventricularly, the POCD mouse model was established, and subsequent morphological changes in hippocampal tissue were assessed using hematoxylin-eosin (HE) staining, Western blot analysis, immunofluorescence, and TUNEL assays, providing confirmation of the network pharmacological enrichment analysis findings.
Regarding potential POCD improvements, EWB pinpointed 110 targets. GO enriched 117 items, and KEGG highlighted 113 pathways. Among these pathways, the SIRT1/p53 signaling pathway is connected to the emergence of POCD. In EWB, quercetin, kaempferol, vestitol, -sitosterol, and 7-methoxy-2-methyl isoflavone exhibit stable conformations with low binding energy to core target proteins IL-6, CASP3, VEGFA, EGFR, and ESR1. Results from animal studies showed the EWB group to have significantly augmented hippocampal apoptosis and reduced Acetyl-p53 protein expression compared to the POCD model group, with the difference being statistically significant (P<0.005).
EWB's multifaceted effects, exhibiting multi-component, multi-target, and multi-pathway synergy, lead to enhanced POCD. Bomedemstat mouse Research has demonstrated that EWB's influence on gene expression within the SIRT1/p53 pathway can improve the frequency of POCD, suggesting a new potential treatment approach and rationale for targeting this condition.
EWB's ability to enhance POCD stems from its multifaceted approach, encompassing multi-component, multi-target, and multi-pathway synergistic effects. Replicated studies have demonstrated that EWB can increase the incidence of POCD by controlling the expression of genes associated with the SIRT1/p53 signaling pathway, providing a new target and rationale for the treatment of POCD.
Remedies for advanced castration-resistant prostate cancer (CRPC), presently utilizing enzalutamide and abiraterone acetate for targeting the androgen receptor (AR) transcription pathway, unfortunately, usually lead to a limited time frame of effectiveness before developing resistance. Bomedemstat mouse Apart from other prostate cancers, neuroendocrine prostate cancer (NEPC) is a lethal form, showcasing AR pathway independence and currently lacking a standard treatment. The traditional Chinese medicine formula, Qingdai Decoction (QDT), displays a variety of pharmacological properties and has been extensively used in treating a range of conditions, including prostatitis, a potential precursor to prostate cancer.
Through this study, we seek to elucidate the anti-tumor role of QDT and the underlying mechanisms in prostate cancer.
For research, CRPC prostate cancer cell models and xenograft mouse models were successfully developed and implemented. To understand how TCMs affected cancer growth and spread, researchers used the CCK-8, wound-healing, and PC3-xenograft mouse model. The toxicity of QDT within the major organs was scrutinized through the application of H&E staining. A network pharmacology approach was adopted to study the intricate compound-target network. Multiple cohorts of prostate cancer patients were used to examine the relationship between QDT targets and patient prognosis. Related proteins and their corresponding mRNAs were identified using western blotting and quantitative real-time PCR. CRISPR-Cas13 technology was instrumental in achieving the gene knockdown.
By integrating functional screening with network pharmacology analysis, CRISPR-Cas13-mediated RNA targeting, and molecular validation in various prostate cancer models and clinical data sets, we determined that Qingdai Decoction (QDT), a traditional Chinese medicine, can restrain cancer development in advanced prostate cancer models, both in laboratory and animal studies, through an androgen receptor-independent mechanism affecting NOS3, TGFB1, and NCOA2.
Beyond identifying QDT as a novel treatment for terminal prostate cancer, the study also formulated a comprehensive integrative research model for examining the mechanisms and roles of traditional Chinese medicines in treating a broader spectrum of diseases.
Beyond identifying QDT as a novel therapeutic agent for lethal-stage prostate cancer, this study also provided a comprehensive framework for integrative research into the roles and mechanisms of Traditional Chinese Medicines for other disease conditions.
Ischemic stroke (IS) is characterized by a high incidence of illness and a high rate of fatalities. Bomedemstat mouse Research conducted previously by our team showcased the diverse pharmacological actions of the bioactive ingredients in Cistanche tubulosa (Schenk) Wight (CT), a traditional medicinal and edible plant, on diseases affecting the nervous system. Yet, the effect of CT scans upon the blood-brain barrier (BBB) in the wake of ischemic strokes (IS) is still not definitively established.
This research project was designed to ascertain CT's curative potential on IS and explore the underlying mechanisms.
Injury was identified in a rat model simulating middle cerebral artery occlusion (MCAO). A seven-day regimen of gavage administrations of CT, at 50, 100, and 200 mg/kg/day, was undertaken. Employing network pharmacology, researchers predicted the pathways and potential targets of CT against IS, which were later validated through subsequent investigations.
The observed neurological dysfunction and blood-brain barrier disruption in the MCAO group, as per the data, were significantly more severe. In addition, CT strengthened BBB integrity and neurological performance, and it safeguarded against cerebral ischemia damage. The involvement of microglia-mediated neuroinflammation in IS was revealed through network pharmacology analysis. Extensive post-hoc analyses confirmed that MCAO was causative of ischemic stroke (IS) by promoting the generation of inflammatory factors and the infiltration of microglial cells. Neuroinflammation was observed to be influenced by CT through the modulation of microglial M1-M2 polarization.
Microglia-mediated neuroinflammation, as a consequence of MCAO-induced ischemic stroke, may be mitigated by CT. Empirical and theoretical data corroborate the efficacy of CT therapy and groundbreaking ideas for the prevention and treatment of cerebral ischemic damage.
The study's results propose a relationship between CT and microglia-driven neuroinflammation, leading to a decrease in ischemic stroke size following MCAO. The efficacy of CT therapy, combined with novel ideas for cerebral ischemic injury prevention and management, is corroborated by theoretical and experimental findings.
Traditional Chinese Medicine frequently utilizes Psoraleae Fructus, a well-established remedy, to warm and fortify the kidneys, thereby providing relief from illnesses like osteoporosis and diarrhea. Nevertheless, the potential for widespread organ damage restricts its practical application.
To pinpoint the constituents of salt-processed Psoraleae Fructus ethanol extract (EEPF), this study sought to systematically investigate its acute oral toxicity and the underlying mechanisms of its acute hepatotoxicity.
UHPLC-HRMS analysis was undertaken in this investigation to identify the components. Kunming mice underwent an acute oral toxicity test, receiving oral gavage doses of EEPF from 385 g/kg up to 7800 g/kg. To understand the mechanisms of EEPF-induced acute hepatotoxicity, a comprehensive analysis was carried out that included body weight, organ index evaluation, biochemical profiles, morphological evaluation, histopathological examination, analysis of oxidative stress, TUNEL assessment, and the examination of mRNA and protein levels of the NLRP3/ASC/Caspase-1/GSDMD signaling pathway.
The EEPF sample yielded 107 compounds, amongst which psoralen and isopsoralen were prominently identified. The acute oral toxicity test revealed the lethal dose, LD.
The EEPF level, in Kunming mice, was quantified at 1595 grams per kilogram. No noteworthy difference in body weight was found between the control group and the surviving mice at the end of the observation period. No statistically significant differences were observed in the organ indexes of the heart, liver, spleen, lungs, and kidneys. Analysis of high-dose mice organs revealed morphological and histopathological changes implicating liver and kidney as the main toxic targets of EEPF. Degeneration of hepatocytes and the presence of lipid droplets and protein casts in kidney tissue were notable findings. The significant upswing in liver and kidney function markers, namely AST, ALT, LDH, BUN, and Crea, served as confirmation. The oxidative stress markers MDA in both the liver and kidney manifested a considerable increase, while SOD, CAT, GSH-Px (liver-restricted), and GSH revealed a marked decrease. Subsequently, EEPF exhibited a rise in TUNEL-positive cells alongside elevated mRNA and protein levels of NLRP3, Caspase-1, ASC, and GSDMD in the liver tissue, concurrent with augmented protein expression of both IL-1 and IL-18. A crucial finding in the cell viability test was that the particular caspase-1 inhibitor successfully reversed EEPF-induced cell death in Hep-G2 cells.
The 107 compounds of EEPF were systematically examined in this research study. The findings of the acute oral toxicity test indicated the lethal dose.
EEP's measured value in Kunming mice was 1595g/kg; the liver and kidneys are possibly the primary organs affected by EEPF's toxicity. Oxidative stress and pyroptotic damage, propagated through the NLRP3/ASC/Caspase-1/GSDMD pathway, inflicted liver injury.
In essence, this research probed the 107 chemical compounds present in EEPF. Acute oral toxicity testing of EEPF in Kunming mice demonstrated an LD50 of 1595 g/kg, with the liver and kidneys as the main organs exhibiting toxicological responses. The NLRP3/ASC/Caspase-1/GSDMD pathway, through oxidative stress and pyroptotic damage, contributed to liver injury.