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Isoliquiritigenin prevents the progression of psoriasis-like symptoms by inhibiting NF-κB and proinflammatory cytokines

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Abstract

Isoliquiritigenin (ISL) is an important flavonoid component of licorice and has been reported to possess anti-inflammatory and antioxidant properties, but its exact mechanism of action remains poorly understood. Previously, we demonstrated that ISL could suppress IL-6 expression in multiple myeloma. Here, we further characterized the anti-inflammatory effects of ISL in several psoriasis models, including the keratin 14/vascular endothelial growth factor (VEGF) transgenic mouse, the imiquimod (IMQ)-induced psoriasis-like mouse, and the human keratinocytes HaCaT and NHEK in vitro. We found that ISL ameliorated the inflammatory process in psoriasis models but not in their respective controls. Moreover, the anti-inflammatory effects of ISL were attributed to the suppression of nuclear factor-κB (NF-κB) activity, which consequently resulted in the reduction of pro-inflammation cytokines IL-6 and IL-8 expression. In conclusion, ISL exhibited anti-inflammatory effects in psoriasis models, by downregulating IL-6 and IL-8 via suppression of NF-κB activity, suggesting that ISL might serve as a potential candidate for treatment of psoriasis and other autoimmune inflammatory diseases.

Key message

  • ISL could ameliorate the inflammatory process of psoriasis.

  • ISL could suppress NF-κB and subsequent production of a series of pro-inflammatory cytokines.

  • Dual-inhibitory activity against IL-6 and IL-8 of ISL is implemented via inhibiting NF-κB.

  • ISL exerts no inhibitory effects on normal human keratinocytes or wild-type Balb/c mice, implying its low toxicity and safety.

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Acknowledgments

We thank Dr. Xiu Teng for the human keratinocyte cell line HaCaT and helpful suggestions in the vitro studies, Congcong Shen for excellent discussions, Xuewen Jin for real-time quantitative PCR analysis and expert suggestions, Weiyong Xu and Juan He for excellent technical assistance in HE staining, Fanghua Li for immunohistochemistry analysis, and Min Wu and John Yun-Chung Chen for the revision of the manuscript.

Conflict of interest

No potential conflicts of interest were disclosed.

Grant support

This study was supported by National Science and Technology Major Projects (No. 2012ZX09103-301-045).

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    Authors and Affiliations

    1. State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, 3-17 Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China

      Yangping Wu, Xiangzheng Chen, Xiaojun Ge, Hongwei Xia, Yuxi Wang, Siyuan Su, Wenting Li, Tinghan Yang, Mingtian Wei, Hang Zhang, Lantu Gou, Jiong Li, Xian Jiang & Jinliang Yang

    2. Department of Laboratory Medicine, First Affiliated Hospital of Zun Yi Medical College, Zun Yi Medical College, Zun Yi, 563003, China

      Xiaojun Ge & Jiong Li

    3. Department of Dermatology, West China Hospital, Sichuan University, Chengdu, 610041, China

      Jiong Li & Xian Jiang

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    1. Yangping Wu
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    Correspondence to Xian Jiang or Jinliang Yang.

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    Yangping Wu and Xiangzheng Chen contributed equally to this work.

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    Wu, Y., Chen, X., Ge, X. et al. Isoliquiritigenin prevents the progression of psoriasis-like symptoms by inhibiting NF-κB and proinflammatory cytokines. J Mol Med 94, 195–206 (2016). https://doi.org/10.1007/s00109-015-1338-3

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