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

Zhen Yang,Tan Li,Wei Wang,Hong Chen,Ying Gao,Yiteng Wang,Bo Cao,Meilun Liu

doi:10.1038/s41598-017-08485-x

Zhen Yang, Tan Li + Show 6 more

Open Access

https://doi.org/10.1038/s41598-017-08485-x

Copy DOI

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.

Highlights

Atopic dermatitis (AD) is a kind of complicated, chronically relapsing inflammatory skin disease, characterized by edema, erythematous, scaly and lichenified lesions
We firstly investigated the effect of Pseudolaric acid B (PB) on the relief of DNFB-induced atopic dermatitis (AD)-like symptoms in NC/Nga mice
We found that total serum IgE levels were significantly increased by repeated DNFB treatment in NC/Nga mice, which was attenuated by PB as well as prednisolone (PD), a well-known anti-inflammatory drug

Summary

Introduction

Atopic dermatitis (AD) is a kind of complicated, chronically relapsing inflammatory skin disease, characterized by edema, erythematous, scaly and lichenified lesions. Several studies evaluating therapies based on natural substances as potential agents have suggested that patients with AD may be benefit from these raw materials[3] One such agent, Pseudolaric acid B (PB), isolated from the extract of the root bark of Pseudolarix kaempferi Gordon (pinaceae), is a diterpene acid with a molecular structure that includes a compact tricyclic core containing a fused [5–7] ring system (polyhydroazulene), an unusual trans substitution pattern at the ring fusion site (C4–C10), and 4 contiguous stereocenters, including one quaternary (C10)[4]. We decided to investigate the anti-inflammatory and immunoregulatory effects of PB using DNFB-induced murine model of AD in NC/Nga mice, and explored the underlying pharmacological mechanisms

Methods

Results

Conclusion