tnfr1 inhibitor r 7050  (MedChemExpress)

Journal: iScience

Article Title: Zhigancao decoction alleviates Parkinson’s disease via inhibiting TNF/NF-κB and Ras/ERK-mediated neuroinflammation and apoptosis

doi: 10.1016/j.isci.2025.114489

Figure Lengend Snippet: ZGCD treatment may alleviate MPTP-induced injury of SN DA neurons by inhibiting the TNF/NF-kB and Ras/ERK pathways (A) WB was used to detect the representative expressions of TNFR1, P65, and p-P65 in SN. (B and C) Statistics of the relative expression level of TNFR1 and p-P65/P65 in SN ( n = 4). (D) WB was used to detect the representative expressions of Ras, ERK, and p -ERK in SN. (E and F) Statistics of the relative expression level of Ras and p -ERK/ERK in SN ( n = 4). (G–K) Representative expression of Tnfr1, Nfkb, Grb2, Ras, and Erk detected by RT-qPCR ( n = 4). ### p < 0.001 vs. Con; n.s., not significant, ∗ p < 0.05, ∗∗ p < 0.01 and ∗∗∗ p < 0.001 vs. MPTP. Data are expressed as mean ± SD.

Article Snippet: To verify the potential connection between TNF/NF-κB and Ras/ERK, we observed the activation changes of the two pathways and the therapeutic effect of ZGCDS after treatment with the TNFR1 inhibitor R-7050 (MCE, China, HY-110203) in vitro .

Techniques: Expressing, Quantitative RT-PCR

Journal: iScience

Article Title: Zhigancao decoction alleviates Parkinson’s disease via inhibiting TNF/NF-κB and Ras/ERK-mediated neuroinflammation and apoptosis

doi: 10.1016/j.isci.2025.114489

Figure Lengend Snippet: ZGCDS exerts neuroprotective effects by inhibiting the activation of TNF/NF-κB and Ras/ERK signaling pathways in SH-SY5Y cells (A) WB was used to detect the representative expressions of TNFR1, P65, and p-P65 in SH-SY5Y cells. (B) Statistics of the relative expression level of TNFR1 in SH-SY5Y cells ( n = 3). (C) Statistics of the relative expression level of p-P65/P65 in SH-SY5Y cells ( n = 3). (D–G) IF was used to analyze the expressions of TNFR1 and p-P65 in SH-SY5Y cells ( n = 3). Scale bars, 200 μm. (H–J) WB analysis of Ras and ERK expression and phosphorylation in SH-SY5Y cells ( n = 6). (K–P) IF was used to analyze the expressions of Grb2, Ras, and p -ERK in SH-SY5Y cells ( n = 3). Scale bars, 100 μm. (Q–S) WB analysis of TNFR1 and P65 expression and phosphorylation in SH-SY5Y cells ( n = 4). (T–W) WB analysis of Grb2, Ras, and ERK expression and phosphorylation in SH-SY5Y cells ( n = 4). ### p < 0.001 vs. Con; n.s., not significant, ∗ p < 0.05, ∗∗ p < 0.01 and ∗∗∗ p < 0.001 vs. MPTP. Data are expressed as mean ± SD.

Article Snippet: To verify the potential connection between TNF/NF-κB and Ras/ERK, we observed the activation changes of the two pathways and the therapeutic effect of ZGCDS after treatment with the TNFR1 inhibitor R-7050 (MCE, China, HY-110203) in vitro .

Techniques: Activation Assay, Protein-Protein interactions, Expressing, Phospho-proteomics

Journal: iScience

Article Title: Zhigancao decoction alleviates Parkinson’s disease via inhibiting TNF/NF-κB and Ras/ERK-mediated neuroinflammation and apoptosis

doi: 10.1016/j.isci.2025.114489

Figure Lengend Snippet: Bioactive compounds (Apigenin, Bisdemethoxycurcumin) from ZGCD may exert anti-PD effects by targeting the TNF/NF-kB and Ras/ERK pathways (A and B) Total ion chromatograms (TICs) of Con in positive (A) and negative (B) ion modes. (C and D) Total ion chromatograms (TICs) of ZGCD-CS in positive (C) and negative (D) ion modes. (E) Venn diagram of serum pharmacochemical analysis. (F) Molecular docking analysis of Apigenin and Bisdemethoxycurcumin with key proteins in the pathway. (G–I) The levels of TNF-α, IL-1β, and IL-6 were detected by ELISA in SH-SY5Y cells ( n = 3). (J–L) WB analysis of TNFR1 and P65 expression and phosphorylation in SH-SY5Y cells ( n = 3). (M–P) WB analysis of Grb2, Ras, and ERK expression and phosphorylation in SH-SY5Y cells ( n = 3). ### p < 0.001 vs. Con; n.s., not significant, ∗ p < 0.05, ∗∗ p < 0.01 and ∗∗∗ p < 0.001 vs. MPTP. Data are expressed as mean ± SD.

Article Snippet: To verify the potential connection between TNF/NF-κB and Ras/ERK, we observed the activation changes of the two pathways and the therapeutic effect of ZGCDS after treatment with the TNFR1 inhibitor R-7050 (MCE, China, HY-110203) in vitro .

Techniques: Enzyme-linked Immunosorbent Assay, Expressing, Phospho-proteomics

Journal: Cell Communication and Signaling : CCS

Article Title: Extracellular vesicles derived from pro-inflammatory M1 macrophages induce an inflammatory and invasive phenotype in melanoma cells

doi: 10.1186/s12964-025-02571-8

Figure Lengend Snippet: M1 EV induced inflammation is activated via NF-ĸB signaling in melanoma cells. A GSEA shows enrichment of multiple inflammation-related pathways in M1 EV vs M0 EV treatment comparison in MV3 cells. NES: normalized enrichment score. Adjusted p -value < 0.05. B The effects of receptor inhibitors and antagonists of TLR4 (10 µM, TAK242, n = 3), TNFR (2 µM, R-7050, n = 2), CXCR1/2 (5 µM, Reparixin, n = 2) and CXCR3 (10 µM, NBI-74330, n = 2) on CXCL8 and IL1B expression on M1 EV -treated MV3 cells. C The effect of NF-ĸB pathway inhibitor (1.5 µM, IKK16, n = 3) on CXCL8 and IL1B expression on 24 h M1 EV -treated MV3 cells. D The effect of NF-ĸB pathway inhibitor (0.5 µM, IKK16, n = 3) on CXCL8 and IL1B expression on 24 h M1 EV -treated COLO800 cells. E Prediction of upstream transcription regulators from Lisa model and their transcriptional response in M1 EV -treated MV3 cells based on M1 EV vs M0 EV comparison from RNA-seq data. F Activation of NF-ĸB p65 on M0, M1 and M2 EV -treated MV3 cells (30 min, n = 3) measured by Western blot and quantified band intensities. Bands were normalized to β-actin. ( G ) Activation of pSTAT3 on M0, M1 and M2 EV -treated MV3 cells (30 min, n = 3) measured by Western blot and quantified band intensities. Bands were normalized to β-actin. The data represent mean ± SD. Statistical significances in B - D were tested with Mann–Whitney non-parametric test and in F - G with Kruskal–Wallis non-parametric test with Dunn’s multiple comparison. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: After pre-treatment, cells were incubated with NF-ĸB pathway inhibitor IKK16 (1.5 μM for MV3 cells and 0.5 μM for COLO800 cells, HY-13687/C8-1282, MedchemExpress), TLR4 inhibitor TAK242 (10 μM, HY-11109/CS-0408, MedchemExpress), TNFR antagonist R-7050 (2 μM, HY-110203, MedchemExpress), CXCR1/2 inhibitor Reparixin (5 μM, HY-15251, MedchemExpress) and CXCR3 antagonist NBI-74330 (10 μM, HY-15320 MedchemExpress) or with equal amounts of DMSO for 30 min, followed by replacement of the fresh media containing a combination of inhibitor or equal amount of DMSO and EV treatment (1 × 10 10 particles/well) for 24 h.

Techniques: Comparison, Expressing, RNA Sequencing, Activation Assay, Western Blot, MANN-WHITNEY