{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T20:10:17Z","timestamp":1778530217874,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan University of Medicine","award":["2015TP1020-2025-01"],"award-info":[{"award-number":["2015TP1020-2025-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Objective: This study aimed to investigate whether pomolic acid (PA), a predicted bioactive metabolite of the Dong botanical drug Madeng\u2019ai (MDA), suppresses inflammatory cytokine expression by inhibiting nuclear factor-\u03baB (NF-\u03baB) pathway activation in a tumor necrosis factor-\u03b1 (TNF-\u03b1)-induced human rheumatoid arthritis fibroblast-like synoviocyte (RA-HFLS) model. Methods: PA content in MDA from different regions and harvest years was quantified via High-Performance Liquid Chromatography (HPLC). Network analysis was employed as a hypothesis-generating tool to predict potential targets and pathways, followed by molecular docking to validate the binding affinity of PA to core targets of the NF-\u03baB pathway, and ADMET prediction to evaluate its pharmacokinetic properties and safety profile. The RA-HFLS inflammatory model was induced by TNF-\u03b1. Cell viability and inflammatory cytokine secretion were assessed using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). NF-\u03baB signaling pathway activation and downstream gene expression were examined by Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. Results: HPLC analysis revealed that MDA samples from Guizhou harvested in 2019 contained the highest PA content (0.1117 mg\/g). Network analysis predicted the NF-\u03baB signaling pathway as a candidate mechanism underlying PA\u2019s potential anti-inflammatory effects. Molecular docking showed that PA stably bound to IKK\u03b2, p65, and I\u03baB\u03b1, while ADMET prediction indicated favorable intestinal absorption, low drug\u2013drug interaction risk, and good genetic safety, albeit with potential hepatotoxicity and reproductive toxicity risks. In the TNF-\u03b1-induced RA-HFLS model, PA dose-dependently inhibited abnormal cell proliferation and significantly reduced the secretion of pro-inflammatory cytokines TNF-\u03b1 and interleukin-6 (IL-6). Mechanistic studies indicated that PA suppressed the activation of the NF-\u03baB signaling pathway, thereby downregulating the mRNA expression of inflammatory genes such as IL-6, TNF-\u03b1, and interleukin-1\u03b2 (IL-1\u03b2). Conclusions: PA, a bioactive metabolite of the Dong botanical drug MDA, may inhibit NF-\u03baB signaling pathway activation, thereby downregulating TNF-\u03b1-induced inflammatory cytokine expression in RA-HFLS, demonstrating its in vitro anti-inflammatory potential.<\/jats:p>","DOI":"10.3390\/molecules31101560","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:35:43Z","timestamp":1778528143000},"page":"1560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pomolic Acid from the Dong Botanical Drug Madeng\u2019ai Suppresses TNF-\u03b1-Induced Inflammatory Response in RA-HFLS by Inhibiting NF-\u03baB Signaling Pathway Activation"],"prefix":"10.3390","volume":"31","author":[{"given":"Sisi","family":"Huang","sequence":"first","affiliation":[{"name":"College of Life Sciences, Jishou University, Jishou 416000, China"},{"name":"Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8849-0280","authenticated-orcid":false,"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Jishou University, Jishou 416000, China"},{"name":"Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3075-3102","authenticated-orcid":false,"given":"Xiaoliang","family":"Xing","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/annrheumdis-2019-216694","article-title":"Is the epidemiology of rheumatoid arthritis changing? 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