Pseudolaric acid B attenuates atopic dermatitis-like skin lesions by inhibiting interleukin-17-induced inflammation

Abstract

Pseudolaric acid B (PB), isolated from the extract of the root bark of Pseudolarix kaempferi Gordon, has been used as a traditional remedy for the treatment of skin diseases. However, the information of PB on atopic dermatitis (AD) remains largely unknown. In the present study, oral administration with PB improved the severity scores of AD-like skin lesions dose-dependently in NC/Nga mice through reducing serum IgE, pro-inflammatory cytokines, and the infiltration of inflammatory cells. In addition, PB significantly attenuated the levels of IL-17 and IL-22, and the proportion of Th17 cells in NC/Nga mice, as well as decreased IL-17-induced inflammation in RAW264.7 cells. Moreover, PB inhibited the phosphorylation of IκBα and miR-155 expression both in NC/Nga mice and in IL-17-stimulated RAW264.7 cells, which could be reversed by GW9662, a specific antagonist for PPARγ. The incorporation of GW9662 reversed the inhibitory effect of PB on the RORγ-mediated activation of the Il17 promoter. Transfection with PPARγ luciferase reporter gene further demonstrated the enhancement of PB on PPARγ transactivation. These findings indicate that PB could ameliorate AD-like skin lesions by inhibiting IL-17-induced inflammation in a PPARγ-dependent manner, which would provide experimental evidence of PB for the therapeutic potential on AD and other inflammatory skin diseases.

Pseudolaric acid B ameliorates synovial inflammation and vessel formation by stabilizing PPARγ to inhibit NF‐κB signalling pathway

“…PAB, containing a compact tricyclic core molecular structure, maintains anti-inflammatory effects in many diseases, including atherosclerosis and skin lesions. 19,42 Here, we observed that PAB decreased M1-polarized macrophages in vivo and in vitro, leading to decreasing synovitis, which suggest PAB could be an potential drug applicable in relieving synovial inflammation during OA.…”

Pseudolaric Acid B Ameliorates Fungal Keratitis Progression by Suppressing Inflammation and Reducing Fungal Load

“…PAB as a natural compound possesses excellent anti-inflammatory activity. It has been proved by previous studies, which showed that PAB ameliorated the severity of dermatitis by reducing proinflammatory cytokines and immune cell infiltration . The treatment with PAB could markedly suppress the expression of inflammatory cytokines (TNF-α, iNOS) and chemokines (MIP-2, CCL2) induced by A.…”

Total Synthesis in the Trost Laboratories: Selected Milestones From the Past Twenty Years

“…For example, 64 reduces hypoxia‐inducible factor 1α (HIF‐1α) protein in tumor cells, which inhibits angiogenesis by diminishing the secretion of vascular endothelial growth factor (VEGF) [69] . Recently, (−)‐pseudolaric acid B has also been shown to attenuate atopic dermatitis‐like skin lesions by inhibiting interleukin‐17‐induced inflammation in NC/Nga mice [70] …”