Nat Prod Sci.  2025 Mar;31(1):1-5. 10.20307/nps.2025.31.1.1.

Anti-pemphigus and Anti-atopic Potentials of Lycopi Herba Extract with MKK3 Inhibitory Activity in Human Keratinocyte HaCaT Cells

Affiliations
  • 1Therapeutics & Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea

Abstract

Pemphigus is autoimmune blistering disease associated with autoantibodies (such as desmoglein 3 antibody) directed against the cell surface of keratinocytes, thereby loss of cell-cell adhesion of keratinocytes. The pathogenesis of pemphigus is currently thought to be mediated by direct inhibition via autoantibodies and subsequent signal transduction involving p38 mitogen activated protein kinase (MAPK) pathway. Several studies have reported both mitogen-activated protein kinase kinase 3 (MKK3) and MKK6 are required for full activation of p38, and we recently reported the activation of MKK3 in pemphigus skin tissue, but not MKK6, suggesting that MKK3 could be a potential therapeutic target for pemphigus vulgaris. Here, we found that AK23 IgG (desmoglein 3 antibody) induced the phosphorylation of MKK3 in human keratinocyte HaCaT cells, and treatment of MKK3-inhibiting Lycopi Herba extract (ELH) with MKK3 kinase IC50 , 12.25 μg/mL significantly inhibited AK23-induced fragmentation of HaCaT cell sheets in a dose-dependent manner without any cytotoxicity. Additionally, ELH exhibited anti-atopic activity. In conclusion, MKK3 could play an important role in blister formation in pemphigus, and the MKK3 inhibition by herbal extracts such as ELH could be a possible therapeutic strategy for treating patients with pemphigus as well as atopic dermatitis.

Keyword

Pemphigus; MKK3; Lycopi Herba; Lycopus lucidus Turcz
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