2. Academic Validation
  3. Khasianine ameliorates psoriasis-like skin inflammation and represses TNF-α/NF-κB axis mediated transactivation of IL-17A and IL-33 in keratinocytes

Khasianine ameliorates psoriasis-like skin inflammation and represses TNF-α/NF-κB axis mediated transactivation of IL-17A and IL-33 in keratinocytes

  • J Ethnopharmacol. 2022 Jun 28;292:115124. doi: 10.1016/j.jep.2022.115124.
Yixi Yang 1,  Yujin Zhang 1,  Xun Chen 1,  Zhou Su 2,  Yu Deng 3,  Qi Zhao 4
Affiliations

Affiliations

  • 1 Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu, 610106, China; Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, 610106, China; School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China.
  • 2 Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu, 610106, China; Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, 610106, China; School of Pharmacy, Chengdu University, Chengdu, 610106, China.
  • 3 Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu, 610106, China; Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, 610106, China; School of Basic Medical Sciences, Chengdu University, Chengdu, 610106, China. Electronic address: [email protected].
  • 4 Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu, 610106, China; Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu, 610106, China; School of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China. Electronic address: [email protected].
PMID: 35183690 DOI: 10.1016/j.jep.2022.115124
Abstract

Ethno-pharmacological relevance: Khasianine is recently identified as a bioactive compound from Solanum nigrum L. (SNL) which is a traditional Chinese herb (named LongKui in China) and has been clinically applied for treating psoriasis in China but with limited knowledge about the active ingredients.

Aim of the study: This study tried to explore the bioactivity of Khasianine and showed that Khasianine possessed highly anti-inflammatory bioactivity which rapidly alleviated psoriasis-like mice skin inflammation.

Materials and methods: Imiquimod induced psoriasis-like mouse model, and human keratinocytes were employed in this study. In vivo, immunohistochemistry and immunofluorescence were performed to evaluate the pathological improvement in psoriatic lesions after Khasianine treatment. In vitro, tumor necrosis factor α (TNF-α) treated HaCaT cells with or without Khasianine, were used to analyze the expression and cellular location of NF-κB p65, the expression of IL-17A and IL-33, and the binding intensity of NF-κB p65 on the promoter of IL-17A and IL-33 to understand the molecular mechanism of Khasianine mediated anti-inflammatory effect.

Results: Khasianine reduced infiltration of CD4+ T helper cells (Th cells) and macrophages in mice psoriatic lesions. Immunohistochemistry analysis revealed that Khasianine reduced TNF-α levels in lesions and suppressed NF-κB p65 activation as well as expression of IL-17A and IL-33 in mice epidermal keratinocytes. Further studies in human keratinocytes demonstrated that Khasianine inhibited TNF-α-induced transcriptional activation (transactivation) of NF-κB p65 such as evicting NF-κB p65 binding from the promoter regions of IL-17A and IL-33 and preventing NF-κB nuclear translocation.

Conclusions: Our results suggested that Khasianine is a potent anti-inflammatory compound with the bioactivity of NF-κB inhibition and is a promising candidate for psoriasis topical therapy.

Keywords

Inflammation; Khasianine; Psoriasis; TNF-α/NF-κB axis; Transactivation.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-N2322
    ≥99.0%, Anti-Tumor Agent