Study on the anti-inflammatory and skin regenerative mechanisms of Xanthium strumarium L. fruit via modulation of atopic signaling pathways

Xanthium strumarium (XSE) is rich in bioactive compounds and has been traditionally used for the treatment of inflammation, pruritus, and ulcerative skin conditions. However, despite its traditional use, the molecular mechanisms underlying its therapeutic effects in inflammatory skin diseases remain poorly understood. This study aimed to evaluate the therapeutic effects of XSE on atopic dermatitis (AD) and to elucidate its underlying molecular mechanisms [ 1 ] [ 2 ] [ 3 ]. An inflammatory environment was induced in HaCaT human keratinocyte cells using tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). XSE treatment effectively alleviated inflammatory responses in HaCaT cells by suppressing NF-κB activation, leading to reduced phosphorylation of p38 MAPK and IκBα. In addition, XSE inhibited activation of both p38 and STAT1 signaling pathways, resulting in downregulation of mRNA expression levels of the inflammatory chemokines TARC and MDC, which are key mediators in AD pathogenesis. mRNA levels were assessed using quantitative real-time PCR (qRT-PCR), and protein expression levels were evaluated by Western blot analysis. Furthermore, XSE promoted nuclear translocation of Nrf2 and activated the Nrf2 signaling pathway via upstream modulation of the PI3K/Akt pathway. This activation subsequently increased the expression of HO-1, an antioxidant enzyme with anti-inflammatory properties. XSE also restored the expression of filaggrin, a key structural protein involved in maintaining the skin barrier, which had been suppressed under inflammatory conditions. In conclusion, this study demonstrated that XSE ameliorates atopic dermatitis by suppressing the NF-κB, STAT1, and p38 MAPK signaling pathways while activating the Nrf2/PI3K/Akt axis. These findings highlight the key molecular mechanisms underlying XSE’s anti-inflammatory and skin barrier-regenerative effects, supporting its potential as a therapeutic agent for inflammatory skin diseases. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany