From TCMSP, TCMID, PubChem, PharmMapper, GeneCards, and OMIM databases, acquire compounds and disease-related targets, and filter to find shared genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) function analysis was performed using R software. 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.
The study of POCD enhancement identified 110 possible targets using EWB methods, 117 items enhanced by GO analysis, and 113 pathways enriched by KEGG analysis. The SIRT1/p53 signaling pathway was found to be linked to cases of POCD. Within EWB, quercetin, kaempferol, vestitol, -sitosterol, and 7-methoxy-2-methyl isoflavone exhibit stable conformational arrangements with low binding energy for core target proteins IL-6, CASP3, VEGFA, EGFR, and ESR1. Rodent studies revealed that, in comparison to the POCD model cohort, the EWB group exhibited a substantial enhancement in hippocampal apoptosis and a marked downregulation of Acetyl-p53 protein expression (P<0.005).
Synergistic effects of multi-component, multi-target, and multi-pathway EWB treatments contribute to improved POCD outcomes. Amlexanox 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.
The multi-faceted nature of EWB, encompassing multiple components, targets, and pathways, results in synergistic effects that improve POCD. Extensive research has shown that EWB can increase the occurrence of POCD by modifying the expression of genes related to the SIRT1/p53 signaling pathway, which establishes a novel therapeutic strategy and groundwork for addressing 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. Amlexanox 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.
This research delves into the anti-tumor potential of QDT and its operational mechanisms in the context of prostate cancer.
CRPC prostate cancer models, including cell lines and xenograft mice, were established for research study. The CCK-8 assay, wound-healing tests, and PC3-xenografted mouse models were used to evaluate the impact of Traditional Chinese Medicines (TCMs) on cancer growth and metastasis. The study of QDT toxicity across a range of major organs was facilitated by the application of H&E staining. The compound-target network underwent a network pharmacology analysis. The prognostic implications of QDT targets in prostate cancer were investigated using data from multiple patient cohorts. Real-time PCR and western blot techniques were used to quantify the expression of related proteins and their mRNA counterparts. Gene expression was lowered via the CRISPR-Cas13 method.
Utilizing functional screening, network pharmacology, CRISPR-Cas13-mediated RNA targeting, and molecular biology validation in diverse prostate cancer models and clinical cohorts, we discovered that Qingdai Decoction (QDT), a traditional Chinese medicine, suppressed tumor growth in advanced prostate cancer models in vitro and in vivo, via an androgen receptor-independent pathway focused on NOS3, TGFB1, and NCOA2.
This study, in addition to recognizing QDT as a novel therapeutic option for end-stage prostate cancer, also devised a comprehensive integrative research paradigm to investigate the roles and mechanisms of traditional Chinese medicines for other diseases.
This study's discovery of QDT as a novel drug for lethal-stage prostate cancer treatment was complemented by the development of a substantial integrative research framework for examining the mechanisms and roles of Traditional Chinese Medicines in other diseases.
Patients with ischemic stroke (IS) experience both high morbidity and high mortality. Amlexanox Our prior investigations into the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) revealed that its bioactive constituents exhibit a diverse array of pharmacological actions against neurological disorders. Despite this, the consequences of computed tomography (CT) on the blood-brain barrier (BBB) post-ischemic stroke (IS) are presently unknown.
This study sought to determine the curative influence of CT on IS and investigate the mechanisms behind it.
The rat model demonstrated injury as a result of middle cerebral artery occlusion (MCAO). For seven days, animals received gavage administrations of CT at escalating dosages, 50, 100, and 200 mg/kg/day. By leveraging network pharmacology, the pathways and potential targets of CT's effect on IS were predicted; subsequent studies then corroborated their significance.
The MCAO group's results highlighted a worsening of neurological dysfunction and a breakdown in the blood-brain barrier. Furthermore, CT enhanced BBB integrity and neurological function, while shielding against cerebral ischemia damage. Network pharmacology identified a possible link between IS and neuroinflammation, with microglia playing a key role. Further investigations demonstrated that the effect of MCAO on ischemic stroke (IS) was mediated by the induction of inflammatory factors and the infiltration of microglia. CT's impact on neuroinflammation was elucidated through its role in modulating microglial M1-M2 polarization.
A noteworthy observation from these findings is CT's possible ability to regulate neuroinflammation spurred by microglia in response to MCAO-induced ischemic stroke. The findings, based on theoretical and experimental analysis, highlight the effectiveness of CT therapy and innovative strategies for the prevention and treatment of cerebral ischemic injuries.
Our observations implied that CT could potentially modulate microglia-induced neuroinflammation, consequently reducing the ischemic lesion size prompted by MCAO. CT therapy's efficacy and novel prevention/treatment concepts for cerebral ischemia are supported by both theoretical and experimental results.
Psoraleae Fructus, a recognized component of Traditional Chinese Medicine, has a long history of use in warming and tonifying the kidneys to address health concerns such as osteoporosis and diarrhea. In contrast, the threat of damage to numerous organs restricts the deployment of this approach.
This study aimed to determine the composition of ethanol extract from salt-processed Psoraleae Fructus (EEPF), systematically evaluate its acute oral toxicity, and investigate the underlying mechanisms of its acute hepatotoxic effects.
In this study, the UHPLC-HRMS analytical procedure was employed for the characterization of components. EEPF was orally administered to Kunming mice in a series of acute oral toxicity tests, with dosages escalating from 385 g/kg to 7800 g/kg. An evaluation of EEPF-induced acute hepatotoxicity and its associated mechanisms involved analysis of body weight, organ indices, biochemical assays, morphological characteristics, histopathological examination, oxidative stress levels, TUNEL assay results, and the mRNA and protein expression profiles of the NLRP3/ASC/Caspase-1/GSDMD signaling pathway.
The research indicated the presence of 107 compounds, such as psoralen and isopsoralen, in EEPF. The LD, as determined by the acute oral toxicity test, was evident.
EEPf measurements in Kunming mice were determined as 1595 grams per kilogram. The surviving mice, at the end of the observation period, demonstrated a body weight comparable to the control group, with no discernible difference. No substantial variations were detected in the organ indexes of the heart, liver, spleen, lung, and kidney. Despite other potential effects, the morphological and histopathological changes within the organs of high-dose mice pointed to liver and kidney as the key sites of EEPF toxicity. The observed damage included hepatocyte degeneration with lipid inclusions and protein casts in kidney tissue. Elevated liver and kidney function parameters, including AST, ALT, LDH, BUN, and Crea, provided significant confirmation. Oxidative stress markers, particularly MDA in the liver and kidney, experienced a substantial rise, in contrast to a significant decrease in SOD, CAT, GSH-Px (liver-specific), and GSH. Importantly, EEPF significantly increased the number of TUNEL-positive cells and the mRNA and protein levels of NLRP3, Caspase-1, ASC, and GSDMD in the liver, along with an increased protein expression of IL-1 and IL-18. The cell viability test demonstrably revealed that the specific caspase-1 inhibitor could reverse Hep-G2 cell death triggered by EEPF.
In summation, this investigation scrutinized the 107 components of EEPF. The findings of the acute oral toxicity test indicated the lethal dose.
Among Kunming mice, the EEPF level reached 1595 grams per kilogram, potentially leading to significant toxic effects primarily in the liver and kidneys. Liver injury was a consequence of oxidative stress and pyroptotic damage, triggered by the NLRP3/ASC/Caspase-1/GSDMD signaling cascade.
The 107 compounds of EEPF were the focus of this comprehensive analysis. 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.