Gentamicin and Citronella-Derived Compounds as Dual Modulators of Inflammation-Associated Targets in Acne Vulgaris.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41226663", "kind": "science-record", "revision": 2, "content_hash": "sha256:a5d13f66f4f65bd120c9a98ca70ab864ad5ea88284422124b00cef6b784c3c98", "created_at": "2026-11-01T20:31:15Z", "updated_at": "2026-11-01T21:36:01Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Gentamicin and Citronella-Derived Compounds as Dual Modulators of Inflammation-Associated Targets in Acne Vulgaris.", "doi": "10.3390/ijms262110628", "pmid": "41226663", "authors": ["Adeola Tawakalitu Kola-Mustapha", "Muhabat Adeola Raji", "Samah H O Zarroug", "George Oche Ambrose"], "journal": "International journal of molecular sciences", "year": 2025, "abstract": "Acne Vulgaris is a chronic inflammatory skin disorder driven by a combination of microbial colonization, immune dysregulation, and disruption of the epidermal barrier. Although isotretinoin remains the most effective treatment, the molecular mechanisms underlying its anti-inflammatory effects are incompletely understood. This study integrates transcriptomic meta-analysis and computational drug screening to identify novel therapeutic targets and candidate compounds for acne management. Three publicly available GEO datasets (GSE6475, GSE10433, GSE11792) were analyzed to identify differentially expressed genes (DEGs) associated with isotretinoin response. Among these, Spectrin beta, non-erythrocytic 1 (SPTBN1) and Signal-induced proliferation-associated 1-like protein 1 (SIPA1L1) emerged as consistently regulated genes with known roles in cytoskeletal organization and immune signaling, respectively. To assess the druggability of these targets, molecular docking was conducted using gentamicin and natural compounds derived from Cymbopogon winterianus, including citronellol, citral, citronellal, and geraniol. Gentamicin demonstrated the strongest binding affinity to SIPA1L1 (-8.6 kcal/mol) and SPTBN1 (-5.9 kcal/mol), forming multiple hydrogen bonds and hydrophobic contacts. Subsequent 100 ns molecular dynamics (MD) simulations confirmed the stability of the gentamicin-protein complexes, as evidenced by favorable RMSD, RMSF, and energy profiles. Interaction energy decomposition revealed strong contributions from electrostatic and van der Waals forces. These findings highlight the potential of gentamicin, and possibly structurally related natural compounds, as modulators of host inflammatory pathways implicated in acne. The study further underscores the utility of integrating transcriptomics, molecular docking, and MD simulation for early-phase therapeutic discovery targeting inflammation and barrier dysfunction in dermatological diseases.", "claims": [{"id": "claim-method", "statement": "However, the random-effects model estimated a non-significant pooled effect size (logFC = −0.01; 95% CI: −0.55 to 0.54; p = 0.98), with high heterogeneity (I2 = 93.8%).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41226663", "locator": "sections[5] \"2.2.1. SPTBN1 (Spectrin Beta, Non-Erythrocytic 1)\" paragraph 2", "quote": "However, the random-effects model estimated a non-significant pooled effect size (logFC = −0.01; 95% CI: −0.55 to 0.54; p = 0.98), with high heterogeneity (I2 = 93.8%)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed in this study are publicly available in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/) under accession numbers GSE6475, GSE10433, and GSE11792.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41226663", "locator": "sections[32] \"Data Availability Statement\" paragraph 2", "quote": "The datasets analyzed in this study are publicly available in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/) under accession numbers GSE6475, GSE10433, and GSE11792."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The pooled meta-analysis revealed a positive but non-significant effect (logFC = 0.07; 95% CI: −0.30 to 0.44; p = 0.71; I2 = 89.7%), reflecting inter-study variability.", "kind": "quantitative", "target": {"value": 0.71, "unit": "p-value", "tolerance": null, "source": "The pooled meta-analysis revealed a positive but non-significant effect (logFC = 0.07; 95% CI: −0.30 to 0.44; p = 0.71; I2 = 89.7%), reflecting inter-study variability."}, "evidence": [{"asset": "source:pmid:41226663", "locator": "sections[6] \"2.2.2. SIPA1L1 (Signal-Induced Proliferation-Associated 1 Like 1)\" paragraph 2", "quote": "The pooled meta-analysis revealed a positive but non-significant effect (logFC = 0.07; 95% CI: −0.30 to 0.44; p = 0.71; I2 = 89.7%), reflecting inter-study variability."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The pooled meta-analysis revealed a positive but non-significant effect (logFC = 0.07; 95% CI: −0.30 to 0.44; p = 0.71; I2 = 89.7%), reflecting inter-study variability.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41226663"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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