Brusatol ameliorates psoriatic dyslipidemia by targeting IL-1β to restore AMPK-mediated lipid homeostasis

Sep 30, 2026

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Psoriasis-associated dyslipidemia drives a self-perpetuating cycle of metabolic dysfunction and chronic inflammation, yet current treatments cannot effectively coordinate these coupled pathological pathways. This study evaluates brusatol, a natural quassinoid, for its ability to restore lipid homeostasis in psoriatic dyslipidemia. In TNF-α-stimulated HaCaT cells and an imiquimod-induced mouse model, brusatol reduces proliferation, inflammation, and systemic lipid abnormalities while avoiding visceral toxicity. Integrated omics and mechanistic assays identify IL-1β as a direct target linking inflammation to lipid dysregulation via IL-1β–AMPK interaction.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

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Introduction

Psoriasis as a systemic disorder

Jiang et al. Chinese Medicine (2026) 21:18 [https://doi.org/10.1186/s13020-025-01287-8](https://doi.org/10.1186/s13020-025-01287-8) Chinese Medicine RESEARCH Open Access Brusatol ameliorates psoriatic dyslipidemiaby targeting IL-1β to restore AMPK-mediated lipid homeostasis Yuankuan Jiang1†, Shumeng Zhang1†, Hewen Guan1†, Kejia lv 1, Jinchao Yu1, Siyi Li 1, Renchuan Jia1, Xiujie Zhang2, Shurong Ma1, Jialin Qu1* and Jingrong Lin2* Abstract Background Psoriasis-associated dyslipidemia presents as a critical comorbidity characterized by a self-perpetuating cycle of metabolic dysfunction and chronic inflammation. Current treatment paradigms lack the capacity to simultaneously modulate these interconnected pathological axes. Here we investigated the efficacy and mechanisms of brusatol (a natural quassinoid derived from Bruceae Fructus) against psoriatic dyslipidemia from the insight of restoring lipid homeostasis. Methods The in vitro efficacy of brusatol was assessed inTNF-α-stimulated HaCaT keratinocytes by evaluating proliferation, apoptosis, and inflammatory responses. In vivo, its therapeutic activity and systemic toxicity were examined in an imiquimod-induced psoriatic mouse model using PASI scoring, histopathological analysis, serum biochemical markers (TC, TG, ALT, AST, Cre), inflammatory cytokines (TNF-α, IL-1β, IL-17A), and BBB-chip analysis. Integrated proteomics and lipidomics of skin tissue and serum revealed dysregulated pathways, and subsequent target engagement was confirmed via molecular docking, CETSA, and DARTS. Mechanistic investigations included IL-1β overexpression, Co-IP, GST pull-down and AMPK pathway analysis (Western blot, qPCR) was explored to delineate the regulatory mechanisms. Results Brusatol dose-dependently suppresses proliferation and inflammatory mediator expression inTNF-α-induced HaCaT keratinocytes, ameliorates skin lesions and systemic dyslipidemia in mice, effectively normalizing serum TC and TG levels without inducing visceral organ toxicity. Further integrated omic analyses and subsequent target validation identified IL-1β as the direct target linking inflammatory signaling and lipid dysregulation. Mechanistic studies uncovered a novel IL-1β–AMPK physical interaction that sequesters AMPK in the cytoplasm. Brusatol disrupts this complex, facilitating AMPK nuclear translocation to suppress lipogenic regulators (SREBP-1c/FASN/ACC1) and potentiate β-oxidation pathways (PPARα/CPT1A), thereby restoring lipid homeostasis. Conclusion Our findings not only establish brusatol as an effective agent for ameliorating psoriatic dyslipidemia, but also unveil a fundamental IL-1β–AMPK interaction that orchestrates inflammation-metabolism crosstalk. †Yuankuan Jiang, Shumeng Zhang and Hewen Guan have contributed equally to this work. *Correspondence: Jialin Qu [jialin_qu@126.com](jialin_qu@126.com)[ ](jialin_qu@126.com)Jingrong Lin [Amy4963@163.com](Amy4963@163.com) © The Author(s) 2026, modified publication 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver)[. The Creative Commons Public Domain D

FAQs

What problem does the study address in psoriasis patients?

The study targets psoriasis-associated dyslipidemia, a comorbidity characterized by metabolic dysfunction and chronic inflammation.

How was brusatol evaluated experimentally?

It was tested in TNF-α-stimulated HaCaT keratinocytes for proliferation, apoptosis, and inflammatory responses, and in an imiquimod-induced psoriatic mouse model using PASI scoring, histology, serum biomarkers, cytokines, and BBB-chip analysis.

What mechanism explains how brusatol restores lipid homeostasis?

The study reports IL-1β as a direct target that physically interacts with AMPK to sequester it in the cytoplasm; brusatol disrupts the complex, promotes AMPK nuclear translocation, suppresses lipogenic regulators, and enhances β-oxidation pathways.

Sep 30, 2026

Uploaded by Stanley