The core target genes of ASI acting against PF were identified using network pharmacology, culminating in the creation of PPI and C-PT networks with Cytoscape Version 37.2. Molecular docking analysis and experimental verification are planned for the signaling pathway, prominently highlighted by a high correlation degree in the GO and KEGG enrichment analysis of differential proteins and core target genes, linked to ASI's inhibition of PMCs MMT.
Proteomic profiling using TMT technology revealed 5727 proteins, of which 70 were found to be downregulated and 178 were upregulated. The levels of STAT1, STAT2, and STAT3 in the mesentery were notably diminished in mice with peritoneal fibrosis in comparison to controls, suggesting a participation of the STAT family in the initiation of peritoneal fibrosis. Following the network pharmacology analysis, 98 ASI-PF-connected targets were established. JAK2, among the top 10 pivotal target genes, stands as a potential therapeutic focus. JAK/STAT signaling may be a pivotal pathway in PF's action, influenced by ASI. Studies of molecular docking revealed a promising potential for ASI to favorably engage with target genes of the JAK/STAT signaling pathway, such as JAK2 and STAT3. The findings from the experiment demonstrated that ASI effectively mitigated Chlorhexidine Gluconate (CG)-induced peritoneal tissue damage and enhanced the phosphorylation of JAK2 and STAT3. In TGF-1 treated HMrSV5 cells, E-cadherin expression was drastically lowered, while there was a considerable upregulation of Vimentin, p-JAK2, α-smooth muscle actin, and p-STAT3 expression. SCH66336 The TGF-1-driven HMrSV5 cell MMT was obstructed by ASI, which decreased JAK2/STAT3 activation and increased p-STAT3 nuclear movement, a response that paralleled the inhibition by the JAK2/STAT3 pathway inhibitor AG490.
Regulating the JAK2/STAT3 signaling pathway, ASI can inhibit PMCs, MMT, and alleviate PF.
The JAK2/STAT3 signaling pathway is targeted by ASI to inhibit PMCs and MMT and alleviate PF.
Benign prostatic hyperplasia (BPH) development is substantially influenced by inflammation. A traditional Chinese medicine, Danzhi qing'e (DZQE) decoction, has a significant history of use in addressing issues related to estrogen and androgen. However, the effect of this on BPH connected to inflammation is still not completely understood.
To explore the impact of DZQE on suppressing inflammation-associated benign prostatic hyperplasia, and to uncover the underlying mechanisms.
Employing experimental autoimmune prostatitis (EAP) to induce benign prostatic hyperplasia (BPH), a dosage of 27g/kg of DZQE was subsequently administered orally for four consecutive weeks. The recorded data included prostate size, weight, and prostate index (PI). Hematoxylin and eosin (H&E) staining was carried out for the purpose of pathological analysis. The immunohistochemical (IHC) method was used for the evaluation of macrophage infiltration. Real-time PCR and ELISA assays were employed to quantify the levels of inflammatory cytokines. A Western blot was employed to assess ERK1/2 phosphorylation. RNA sequencing analyses were used to examine the contrasting mRNA expression patterns in benign prostatic hyperplasia (BPH) cells induced by estrogen/testosterone (E2/T) versus those induced by EAP. In vitro, human prostate epithelial BPH-1 cells were primed with a conditioned medium from THP-1-derived M2 macrophages. These cells were then sequentially exposed to Tanshinone IIA, Bakuchiol, the ERK1/2 inhibitor PD98059 or the ERK1/2 agonist C6-Ceramide. SCH66336 Subsequently, Western blotting in conjunction with the CCK8 assay was instrumental in determining ERK1/2 phosphorylation and cell proliferation.
DZQE demonstrated a significant inhibitory effect on prostate enlargement and a decrease in the PI value in experimental animals (EAP rats). The pathological examination indicated that DZQE successfully decreased prostate acinar epithelial cell proliferation by reducing CD68 levels.
and CD206
Prostate macrophage infiltration. EAP rats' prostate and serum cytokine levels of TNF-, IL-1, IL-17, MCP-1, TGF-, and IgG were substantially decreased by DZQE. mRNA sequencing data also highlighted increased expressions of inflammation-related genes specifically in EAP-induced benign prostatic hyperplasia, a phenomenon not observed in E2/T-induced benign prostatic hyperplasia. E2/T- and EAP-induced benign prostatic hyperplasia (BPH) displayed expression of genes that are connected to ERK1/2. Benign prostatic hyperplasia (BPH) induced by EAP is closely linked to the ERK1/2 signaling pathway, which demonstrated activation in the EAP group and deactivation in the DZQE group. In vitro studies demonstrated that the active components of DZQE Tan IIA and Ba suppressed M2CM-induced BPH-1 cell proliferation, exhibiting a similar effect to the ERK1/2 inhibitor PD98059. Simultaneously, Tan IIA and Ba prevented M2CM-triggered ERK1/2 activation in BPH-1 cells. Following the re-activation of ERK1/2 by its activator C6-Ceramide, the inhibitory effects of Tan IIA and Ba on the proliferation of BPH-1 cells were negated.
Through the orchestration of Tan IIA and Ba, DZQE subdued inflammation-associated BPH, specifically through regulation of the ERK1/2 signaling system.
Inflammation-associated BPH was suppressed by DZQE, which regulated ERK1/2 signaling pathways via Tan IIA and Ba.
Postmenopausal women exhibit a significantly higher rate, three times greater than men's, of dementias, including Alzheimer's disease. Plant-derived compounds, phytoestrogens, are recognized for their potential to mitigate menopausal symptoms, including cognitive decline. Phytoestrogen-rich Millettia griffoniana, as described by Baill, is employed in addressing both menopausal difficulties and dementia.
Determining the estrogenic and neuroprotective impact of Millettia griffoniana treatment on ovariectomized (OVX) rats.
The lethal dose 50 (LD50) of M. griffoniana ethanolic extract was determined through in vitro MTT assays conducted on human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells, evaluating its safety.
The estimation was carried out, adhering to the OECD 423 guidelines. To investigate estrogenicity, in vitro experiments utilized the well-established E-screen assay on MCF-7 cells, which was complemented by an in vivo study. Four groups of ovariectomized rats received 75, 150, or 300 mg/kg of M. griffoniana extract, or a standard dose of 1 mg/kg body weight estradiol for three days. Subsequent analysis concentrated on changes in uterine and vaginal morphology. For assessing the neuroprotective effect, Alzheimer's-type dementia was induced by administering scopolamine (15 mg/kg B.W., i.p.) four times a week over four days. For two weeks, daily administration of M. griffoniana extract and the standard drug piracetam was used to evaluate the extract's neuroprotective activity. The analysis concluded with assessment of learning, working memory, brain oxidative stress (SOD, CAT, MDA), acetylcholine esterase (AChE) activity and hippocampal histopathological changes.
The 24-hour incubation of mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract resulted in no observable toxic effects, and its lethal dose (LD) similarly showed no adverse effects.
A quantity greater than 2000mg/kg was found. The extract's estrogenic activity was observed in both laboratory and live animal tests; a substantial (p<0.001) increase in MCF-7 cell culture was evident, accompanied by elevated vaginal epithelial thickness and uterine weight, especially with the 150mg/kg BW dose, contrasted with untreated OVX rats. Through improvements in learning, working, and reference memory, the extract mitigated the scopolamine-induced memory impairment in rats. The hippocampus exhibited an upregulation of CAT and SOD expression, alongside a reduction in MDA levels and AChE activity. The extract, in addition, exhibited a reduction in neuronal cell death within the hippocampal structures, specifically in the CA1, CA3, and dentate gyrus. The M. griffoniana extract, analyzed by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS), showed the presence of numerous phytoestrogens.
The observed anti-amnesic activity of M. griffoniana's ethanolic extract could stem from its estrogenic, anticholinesterase, and antioxidant characteristics. SCH66336 These results, therefore, offer an explanation for the prevalent use of this plant in therapies targeting menopausal symptoms and dementia.
The anti-amnesic action of M. griffoniana ethanolic extract may result from its concurrent estrogenic, anticholinesterase, and antioxidant attributes. These findings accordingly shed light on the basis for this plant's frequent use in the management of menopausal complaints and dementia.
Potential adverse effects of traditional Chinese medicine injections include pseudo-allergic reactions (PARs). Nevertheless, within the realm of clinical practice, immediate allergic responses and physician-attributed reactions (PARs) to these injections are frequently not distinguished.
This investigation sought to categorize the responses to Shengmai injections (SMI) and explore the underlying potential mechanism.
Evaluation of vascular permeability was conducted in a mouse model. The p38 MAPK/cPLA2 pathway was identified through western blotting, while UPLC-MS/MS was used to analyze the metabolomic and arachidonic acid metabolite (AAM) profiles.
Exposure to intravenous SMI, at varying doses, triggered edema and exudative reactions, specifically in the ears and lungs, rapidly. PARs were the likely mediators of these non-IgE-dependent reactions. The metabolomic profile of SMI-treated mice indicated changes in endogenous substances, the arachidonic acid (AA) metabolic pathway demonstrating the strongest impact. SMI led to a considerable rise in lung AAM levels, specifically encompassing prostaglandins (PGs), leukotrienes (LTs), and hydroxy-eicosatetraenoic acids (HETEs).