2. Academic Validation
  3. Elephantopus scaber attenuates MC903-caused atopic dermatitis and decreases TNF-α/IFN-γ-induced chemokines by suppressing MKP-1-mediated AP-1 signaling in keratinocytes

Elephantopus scaber attenuates MC903-caused atopic dermatitis and decreases TNF-α/IFN-γ-induced chemokines by suppressing MKP-1-mediated AP-1 signaling in keratinocytes

  • J Ethnopharmacol. 2025 Aug 29:352:120267. doi: 10.1016/j.jep.2025.120267.
Chenchen Zang 1,  Min Cai 2,  Qian Chen 3,  Meng Yu 4,  Jingjing Yan 5,  Yilin Guo 6,  Muqing Wang 7,  Congyu Wu 8,  Yuan Gao 9,  Yun Qi 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 2016185836@qq.com.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 1978048693@qq.com.
  • 3 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 1176466080@qq.com.
  • 4 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: myu@implad.ac.cn.
  • 5 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 2281570894@qq.com.
  • 6 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 1095313476@qq.com.
  • 7 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 1322903406@qq.com.
  • 8 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: 2201034890@qq.com.
  • 9 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: ygao@implad.ac.cn.
  • 10 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. Electronic address: yqi@implad.ac.cn.
PMID: 40633861 DOI: 10.1016/j.jep.2025.120267
Abstract

Ethnopharmacological relevance: Atopic dermatitis (AD) is an inflammatory skin disease. Elephantopus scaber L. (E.scaber) is a traditional Chinese medicine for treating inflammatory skin diseases. However, the effects and mechanisms of E.scaber on AD remain unclear.

Aim of the study: To evaluate the effects and underlying mechanisms of the ethanol extract of E.scaber (ESE) on AD.

Methods: MC903 (calcipotriol) was painted on the ears of mice for continuous 9 days. The application area exhibited AD-like skin lesions, and the degree of cutaneous inflammation was evaluated. Histopathology assessed epidermal thickness and mast cell infiltration. Cytokine and chemokine levels in inflamed skin were measured by ELISA. TNF-α/IFN-γ-activated human keratinocytes (HaCaT) were used for in vitro studies. The cells were transfected with reporter plasmids for AP-1, NF-κB, or STAT1 signaling assay. RT-qPCR and Western blot were used for determining the transcription and translation levels of chemokines.

Results: MC903 caused AD-like skin lesions, while local application of ESE decreased ear (epidermal) thickness, reduced the dermatitis score, and lowered the number of mast cells. Furthermore, it suppressed the levels of IgE, Th2-related cytokines (IL-4 and IL-13), and chemokines (CCL22, TSLP, and CCL2) in inflamed skin. In TNF-α/IFN-γ-activated HaCaT cells, ESE reduced the transcription and translation levels of multiple chemokines. Furthermore, it inhibited the activation of AP-1 signaling by enhancing the expression of MKP-1 to reduce the phosphorylation levels of p38 and JNK.

Conclusion: ESE alleviates the skin lesions of AD mice through suppressing Th2-related chemokines and cytokines. In vitro, it reduces the levels of Th2-related chemokines in TNF-α/IFN-γ-activated HaCaT cells, which is attributed to the inhibition of MKP-1-mediated AP-1 signaling.

Keywords

Atopic dermatitis; Elephantopus scaber L.; Keratinocyte; MKP-1; Th2 chemokines.

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