Search Results (4)

Against the backdrop of rising multidrug-resistant Acinetobacter baumannii (MDR AB) threats, this study explores the in vitro antibacterial activity and mechanism of Senecio scandens (a Miao ethnic medicinal herb) crude extract. Using 10 clinical MDR AB strains, we reassessed antibiotic sensitivity and then applied microbroth dilution to determine MIC/MBC, time-kill curves for bactericidal kinetics, and SEM/TEM for structural changes. Proteomics identified downregulated proteins, cross-referenced with VFDB/CARD to target membrane-related proteins (msbA, lptD), while molecular docking validated the strong binding of linarin/hyperoside to these targets. qPCR confirmed lptD/msbA mRNA downregulation (p < 0.05) by linarin/hyperoside (MIC = 312.5 μmol/L). The extract showed concentration-dependent bactericidal effects (MIC = 640 μg/mL), disrupting cell wall/membrane integrity. This study first reveals that linarin and hyperoside inhibit MDR AB by downregulating lptD/msbA, compromising outer membrane integrity, offering novel therapeutic candidates. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Jacaranone derived from Senecio scandens, a traditional Chinese medicine used for centuries, has been documented to exhibit anti-inflammatory and antiproliferative properties in various tumor cell lines. However, the mechanism of action and relationship between inflammation and apoptosis induced by jacaranone remain inadequately elucidated. In this study, the targets of jacaranone and cancer were identified from various databases, while potential targets and pathways were predicted through the analysis of the protein–protein interactions (PPI) network and pathway enrichment. Through a comprehensive network pharmacology analysis and corroborating experimental findings, we revealed that jacaranone induces tumor cell death by fine-tuning the tumor necrosis factor receptor 1 (TNFR1) downstream signaling pathway. TNFR1 serves as a key node that assembles into complexes I and II, regulating pathways including the nuclear factor (NF)-κB signaling pathway and the cell apoptosis pathway, which play crucial roles in cellular life activities. Jacaranone successfully guides survival signaling pathways to apoptotic mechanisms by inhibiting the assembly of complex I and promoting the formation of complex II. In particular, the main action mechanism of jacaranone lies in inducing the degradation of the inhibitor of apoptosis protein (cIAP)-2. cIAP-2 serves as an E3 ubiquitin ligase that ubiquitinates receptor-interacting serine/threonine-protein kinase 1 (RIPK1), thereby hindering the formation of complex I and effectively reducing the phosphorylation of Inhibitor of κB kinase (IKK) β. When the deubiquitylation process of RIPK1 is triggered, it may promote the formation of complex II, which ultimately leads to cell apoptosis. This fully demonstrates the key role of jacaranone in regulating TNFR1 complexes, especially through the degradation of cIAP-2. Taken together, jacaranone hinders the assembly of TNFR1 complex I and promotes the formation of complex II to induce apoptosis of cancer cells. Our findings unveil a novel mechanism underlying jacaranone, while also presenting a fresh approach for the development of new pharmaceuticals. Full article

Background: Hepatocellular carcinoma (HCC), a prevalent form of primary liver malignancy, arises from liver-specific hepatocytes. Senecio scandens Buch.-Ham(Climbing senecio) is a bitter-tasting plant of the Compositae family with anti-tumor properties. This study aims to identify the molecular targets and pathways through which Climbing senecio regulates HCC. Methods: Active ingredients of Climbing senecio were collected from four online databases and mapped to relevant target databases to obtain predicted targets. After recognizing the key pathways through which Climbing senecio acts in HCC. Gene expression data from GSE54238 Underwent differential expression and weighted gene correlation network analyses to identify HCC-related genes. The “Climbing senecio-Hepatocellular Carcinoma Targets” network was constructed using Cytoscape 3.10.1 software, followed by topology analysis to identify core genes. The expression and distribution of key targets were evaluated, and the differential expression of each key target between normal and diseased samples was calculated. Moreover, single-cell data from the Gene Expression Omnibus (GSE202642) were used to assess the distribution of Climbing senecio’s bioactive targets within major HCC clusters. An intersection analysis of these clusters with pharmacological targets and HCC-related genes identified Climbing senecio’s primary targets for this disease. Cell communication, receiver operating characteristic (ROC)analysis, survival analysis, immune filtration analysis, and molecular docking studies were conducted for detailed characterization. Results: Eleven components of Climbing senecio were identified, along with 520 relevant targets, 300 differentially expressed genes, and 3765 co-expression module genes associated with HCC. AKR1B1, CA2, FOS, CXCL2, SRC, ABCC1, and PLIN1 were identified within the intersection of HCC-related genes and Climbing senecio targets. TGFβ, IL-1, VEGF, and CXCL were identified as significant factors in the onset and progression of HCC. These findings underscore the anti-HCC potential and mode of action of Climbing senecio, providing insights into multi-targeted treatment approaches for HCC. Conclusions: This study revealed that Climbing senecio may target multiple pathways and genes in the process of regulating HCC and exert potential drug effects through a multi-target mechanism, which provides a new idea for the treatment of HCC. However, the research is predicated on network database analysis and bioinformatics, offering insights into HCC therapeutic potential while emphasizing the need for further validation. Full article