Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Triptolide promotes the clearance of intracellular SA and MRSA. (A) Schematic diagram of the procedure for screening TCM monomers that modulate intracellular SA clearance. (B) Representative results illustrating the effects of 15 TCM monomers that promoted intracellular SA clearance and 2 that inhibited it. DMSO and methicillin were used as the negative and positive controls, respectively. Intracellular survival analysis of SA (C) and MRSA (D) in iBMDMs treated with different concentrations of the designated TCM monomers. Data are shown as mean ± SEM [n = 3 in (B–D) ]. ***0.0001 ≤ P < 0.001; **** P < 0.0001 [one-way ANOVA with Dunnett’s post hoc test for (B–D) ].

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques:

Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Triptolide triggers activation of the apoptotic signaling pathway. Gene Ontology (GO) enrichment analysis of differentially expressed genes (A) and proteins (B) in SA-infected iBMDMs treated with triptolide versus DMSO. Volcano maps depicting differentially expressed genes (C) and proteins (D) in SA-infected iBMDMs treated with triptolide versus DMSO. (E) Representative results of fluorescence-activated cell sorting (FACS)-based analysis for percentages of apoptotic cells. Quantification of apoptosis in SA (F) - and MRSA (G) -infected cells treated with DMSO, triptolide, or methicillin. Immunoblotting analysis of cleaved caspase-3 in SA (H) - and MRSA (I) -infected cells treated with DMSO, triptolide, or methicillin. Q-VD-OPh was used as the caspase inhibitor. Data are shown as mean ± SEM [n = 4 in (F,G) ]. **** P < 0.0001 [two-way ANOVA with Tukey’s post-hoc test for (F,G) ].

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques: Activation Assay, Infection, Fluorescence, FACS, Western Blot

Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Triptolide induces apoptosis through targeting XIAP. (A) Measurement of triptolide binding affinity to Bcl2, STAT1, and XIAP by octet. (B) Molecular docking analysis between triptolide and XIAP. The BIR2 and BIR3 domains of XIAP are shown in orange. RMSD (C) and Rg (D) curves depicting the interaction between triptolide and XIAP. RMSD, root mean square deviation; Rg, radius of gyration. (E) Blocking assay to assess the effect of triptolide or SM-164 on XIAP-caspase-3/9 interaction. Quantification of apoptosis in SA (F) - and MRSA (G) -infected cells treated with DMSO, triptolide, SM-164, triptolide in combination with SM-164, or methicillin. Data are shown as mean ± SEM [n = 3 in (F,G) ]. **0.001 ≤ P < 0.01; ***0.0001 ≤ P < 0.001; **** P < 0.0001 [one-way ANOVA with Dunnett’s post hoc test for (F,G) ].

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques: Binding Assay, Blocking Assay, Infection

Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Triptolide reduces SA and MRSA survival and attenuates host inflammatory pathology in vivo (A) Diagram of the experimental design in mice. Bacterial loads of SA (B) and MRSA (C) in the lungs of C57BL/6N mice treated with PBS, triptolide, or methicillin. (D) Representative images and quantitation for inflammatory areas in the lungs of C57BL/6N mice treated as in (B,C) . Scale bar, 100 μm. (E) Immunofluorescence and quantitation for cleaved caspase-3 (red) in the lung macrophages (green) of C57BL/6N mice treated as in (B,C) . Scale bar, 20 μm. Data are shown as mean ± SEM [n = 4 in (B–E) ]. *0.01 ≤ P < 0.5; **0.001 ≤ P < 0.01; ***0.0001 ≤ P < 0.001; **** P < 0.0001 [one-way ANOVA with Tukey’s post-hoc test for (B–E) ].

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques: In Vivo, Quantitation Assay, Immunofluorescence

Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Transcriptomics and proteomics analysis revealing that triptolide induces apoptosis in lung macrophages from mice infected with SA or MRSA. (A) GO enrichment analysis of differentially expressed genes in SA-infected mice treated with PBS, triptolide, or methicillin. (B) GO enrichment analysis of differentially expressed genes in MRSA-infected mice treated with PBS, triptolide, or methicillin. (C) GO enrichment analysis of differentially expressed proteins in mice treated as in (A) . (D) GO enrichment analysis of differentially expressed proteins in mice treated as in (B) .

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques: Transcriptomics, Infection

Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Metagenomics analysis revealing that triptolide maintains microbiota homeostasis in mice infected with SA or MRSA. (A) Alpha (α) diversity among SA-infected mice treated with PBS, triptolide, or methicillin. (B) Alpha (α) diversity among MRSA-infected mice treated with PBS, triptolide, or methicillin. (C) Differential analysis of gut microbial composition among SA-infected mice treated as in (A) . (D) Differential analysis of gut microbial composition among MRSA-infected mice treated as in (B) .

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques: Metagenomics, Infection

Journal: Frontiers in Pharmacology

Article Title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while maintaining gut microbiota homeostasis

doi: 10.3389/fphar.2026.1834558

Figure Lengend Snippet: Metabolomics analysis revealing that triptolide enhances immunomodulatory metabolites against infections. (A) Partial least-squares discriminant analysis (PLS-DA) score plots of metabolites from SA-infected mice treated with PBS, triptolide, or methicillin. (B) PLS-DA score plots of metabolites from MRSA-infected mice treated with PBS, triptolide, or methicillin. (C) Heatmap of differential metabolites among SA-infected mice treated as in (A) . (D) Heatmap of differential metabolites among MRSA-infected mice treated as in (B) .

Article Snippet: For transcriptomics analysis, total RNA was extracted from iBMDMs infected with SA and treated with DMSO or triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, or methicillin according to the TRIzol® manual (Life Technologies, 15596-026).

Techniques: Infection