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To elucidate the active ingredients and potential mechanism of Solanum lyratum in the treatment of rheumatoid arthritis (RA), we employed a comprehensive strategy that combined network pharmacology and molecular docking. First, we systematically retrieved relevant compounds from S. lyratum documented in the literature. We obtained RA-related targets by querying GeneCards, DisGeNET, and the OMIM database. Subsequently, we constructed drug-compound-target and protein-protein interaction (PPI) networks to predict the promising protein targets of S. lyratum and identify the primary interactions between these protein targets and compounds. To validate our predicted candidate targets, we employed docking techniques. Finally, we conducted an in vitro intervention and validation using the ethyl acetate extract of S. lyratum on human RA synovial fibroblasts (MH7A). Our analysis identified a total of 41 potential active compounds and 126 intersecting pharmacological targets. GO enrichment analysis revealed that positive regulation of gene expression, response to hypoxia, and apoptotic processes were closely associated with S. lyratum treatment in RA. KEGG pathway analysis suggested that the TNF signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and Toll-Like receptor signaling pathway might play a pivotal role in S. lyratum intervention in RA. Consequently, key targets could include AKT1, TP53, VEGF, CASP3, TNF, and IL6. Molecular docking analysis indicated that diosgenin, strychnine, solamargine, solamarine, solasodine, and ursolic acid exhibited strong binding affinities with STAT3, JUN, MAPK1, TNF, TP53, IL6, MAPK8, IL1B, MMP1, and MMP3. These active compounds in S. lyratum had the potential to regulate multiple signaling pathways and target molecules, thereby exerting preventive and therapeutic effects in RA. In our in vitro experiment, we observed that the ethyl acetate extract of S. lyratum inhibited the proliferation of MH7A cells and reduced the release of cytokines. These experimental results aligned with the predictions generated through the network pharmacology approach. This study not only provided a theoretical foundation for the use of S. lyratum in the treatment of RA but also offered valuable insights for further investigations into the action mechanisms of Chinese herbal extract compounds. [ABSTRACT FROM AUTHOR]

A total of 21 compounds were isolated from the seeds of Capparis masaikai and identified as oxazolidine-2-thione (1), succinimide (2), catechol (3), octathiocane (4), monoethanolamine (5), 3-hydroxypropanenitrile (6), L-arabinose (7), 1,2,3-propanetriol (8), drummondol (9), spionoside B (10), adenosine (11), corchoionoside C (12), coniferin (13), syringin (14), cis-syringin (15), dihydrosyringin (16), indole-3-carboxylic acid (17), β-D-glucopyranosyl indole-3-carboxylic acid (18), 6-hydroxyindole-3-carboxylic acid β-D-glucopyranosyl ester (19), linoleis monoglyceride (20), and triolein (21). Their structures were identified based on physicochemical property and spectroscopic analysis, including MS, NMR, and single-crystal X-ray crystallographic data. Compounds 2–10 and 12–21 were isolated from C. masaikai for the first time. [ABSTRACT FROM AUTHOR]

SLIT2 is a secreted polypeptide that guides migration of cells expressing Roundabout 1 and 2 (ROBO1 and ROBO2) receptors. Herein, we investigated SLIT2/ROBO signaling effects in gliomas. In patients with glioblastoma (GBM), SLIT2 expression increased with malignant progression and correlated with poor survival and immunosuppression. Knockdown of SLIT2 in mouse glioma cells and patient-derived GBM xenografts reduced tumor growth and rendered tumors sensitive to immunotherapy. Tumor cell SLIT2 knockdown inhibited macrophage invasion and promoted a cytotoxic gene expression profile, which improved tumor vessel function and enhanced efficacy of chemotherapy and immunotherapy. Mechanistically, SLIT2 promoted microglia/macrophage chemotaxis and tumor-supportive polarization via ROBO1- and ROBO2-mediated PI3K-γ activation. Macrophage Robo1 and Robo2 deletion and systemic SLIT2 trap delivery mimicked SLIT2 knockdown effects on tumor growth and the tumor microenvironment (TME), revealing SLIT2 signaling through macrophage ROBOs as a potentially novel regulator of the GBM microenvironment and immunotherapeutic target for brain tumors. [ABSTRACT FROM AUTHOR]

A new 18-norschiartane bisnortriterpenoid, 12-angeloyl wuweizidilactone I (1) and nine known compounds, wuweizidilactone I (2), wuweizidilactone G (3), deoxychizandrin (4), sasanquin (5), orcinol-O-β-D-glucopyranoside (6), okanin-4-methyl ether-3'-O-β-Dglucopyranoside (7), evemic acid (8), juglansol A (9) and 2-acetoxybenzyl benzoate (10), were isolated from the fruits of Schisandra Chinensis. Their structures were established by a combination of spectroscopic data analysis in addition to comparison with literature data. Compound 1 was new, and compounds 6–10 were isolated from Schisandrae Chinensis for the first time. [ABSTRACT FROM AUTHOR]

To unravel the active components and potential mechanisms of Astilbe chinensis in treating rheumatoid arthritis (RA), we employed a comprehensive strategy that combined network pharmacology and biological activity verification. Firstly, we identified the relevant compounds in A. chinensis from the literature, and RA-related targets were gathered through DisGeNET, GeneCards, and OMIM databases. Subsequently, compound-target and protein-protein interaction networks were constructed to predict the key compounds and promising protein targets of A. chinensis. Finally, these predictions were validated through in vitro anti-inflammatory activity experiments. A total of 29 potential active compounds and 117 intersecting pharmacological targets were identified. Among them, key active compounds included 3β,6β-dihydroxy olean-12-en-27-oic acid (astilbic acid), 3β-acetoxyolean-12-en-27-oic acid (3-acetyl oleanolic acid), 3β-hydroxyurs-12-en-27-oic acid, 4-O-galloylbergenin, and (+)/(-)-catechin. Key targets were identified as AKT1, MMP9, EGFR, CASP3, and HSP90AA1. GO enrichment analysis indicated that signal transduction, proteolysis, and negative regulation of the apoptotic process were closely associated with A. chinensis treatment in RA. KEGG pathway analysis indicated that pathways in cancer, osteoclast differentiation, and endocrine resistance might be crucial for A. chinensis intervention in RA. This finding suggested that multiple components in A. chinensis could regulate various signaling pathways and targets, playing preventive and therapeutic roles in RA. In vitro experiments demonstrated that A. chinensis extracts inhibited the secretion of inflammatory factors (NO, TNF-α, and IL-6) and significantly suppressed the expression of inducible nitric oxide synthase (iNOS), IL-6, and TNF-α mRNA in LPS-induced RAW 264.7 cells. Collectively, our findings not only established the theoretical basis for the efficacy of A. chinensis in treating RA but also provided a direction for subsequent research. [ABSTRACT FROM AUTHOR]

Renal tubular cell apoptosis and tubular dysfunction is an important process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney damage associated with glucotoxicity. Curcumin has been demonstrated to possess potent anti-apoptotic properties. However, the roles of curcumin in renal epithelial cells are yet to be defined. The present study investigated advanced glycation or glycoxidation end-product (AGE)-induced toxicity in renal tubular epithelial cells via several complementary assays, including cell viability, cell apoptosis and cell autophagy in the NRK-52E rat kidney tubular epithelial cell line. The extent of apoptosis was significantly increased in the NRK-52E cells following treatment with AGEs. The results also indicated that curcumin reversed this effect by promoting autophagy through the phosphoinositide 3-kinase/AKT serine/threonine kinase signaling pathway. These conclusions suggested that curcumin exerts a renoprotective effect in the presence of AGEs, at least in part by activating autophagy in NRK-52E cells. Collectively, these findings indicate that curcumin not only exerts renoprotective effects, however may also act as a novel therapeutic strategy for the treatment of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) are slowly dividing astrocytes that are intimately associated with capillary endothelial cells in the subventricular zone (SVZ) of the brain. Functionally, members of the vascular endothelial growth factor (VEGF) family can stimulate neurogenesis as well as angiogenesis, but it has been unclear whether they act directly via VEGF receptors (VEGFRs) expressed by neural cells, or indirectly via the release of growth factors from angiogenic capillaries. Here, we show that VEGFR-3, a receptor required for lymphangiogenesis, is expressed by NSCs and is directly required for neurogenesis. Vegfr3:YFP reporter mice show VEGFR-3 expression in multipotent NSCs, which are capable of self-renewal and are activated by the VEGFR-3 ligand VEGF-C in vitro. Overexpression of VEGF-C stimulates VEGFR-3-expressing NSCs and neurogenesis in the SVZ without affecting angiogenesis. Conversely, conditional deletion of Vegfr3 in neural cells, inducible deletion in subventricular astrocytes, and blocking of VEGFR-3 signaling with antibodies reduce SVZ neurogenesis. Therefore, VEGF-C/VEGFR-3 signaling acts directly on NSCs and regulates adult neurogenesis, opening potential approaches for treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]