Isoalantolactone suppresses LPS-induced inflammation by inhibiting TRAF6 ubiquitination and alleviates acute lung injury

Acta Pharmacologica Sinica
Yun-He DingFeng Qian

Abstract

Isoalantolactone (IAL) is a sesquiterpene lactone extracted from roots of Inula helenium L and has shown anti-inflammatory effects. In this study we investigated the therapeutic effects of IAL on acute lung injury (ALI) and elucidated the mechanisms underlying its anti-inflammation potential in vitro and in vivo. Treatment with lipopolysaccharide (LPS, 100 ng/mL) drastically stimulated production of inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6 in mouse bone marrow-derived macrophages (BMDMs), which was dose-dependently suppressed by pretreatment with IAL (2.5, 5, 10, 20 μM). We further revealed that IAL suppressed LPS-induced NF-κB, ERK, and Akt activation. Moreover, the downregulation of non-degradable K63-linked polyubiquitination of TRAF6, an upstream transcription factor of NF-κB, contributed to the anti-inflammatory effects of IAL. ALI was induced in mice by intratracheal injection of LPS (5 mg/kg). Administration of IAL (20 mg/kg, i.p.) significantly suppressed pulmonary pathological changes, neutrophil infiltration, pulmonary permeability, and pro-inflammatory cytokine expression. Our results demonstrate that IAL is a potential therapeutic reagent against inflammation and ALI.

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Citations

Jan 16, 2019·Acta Pharmacologica Sinica·Yun-Tian ChenFeng Qian
Apr 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yunjuan NiePeng Zhao
Aug 14, 2020·Neural Regeneration Research·Wan ZhangYing Tian
Dec 29, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lucas Amaral-MachadoEryvaldo S T Egito
May 11, 2020·International Immunopharmacology·Jinwei LuRongxin He
Mar 29, 2021·Toxicology and Applied Pharmacology·Hong-Xia LiShao-Hua Cai
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Karin Lunz, Iris Stappen
Aug 10, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Eleni MarkoutsaSubhra Mohapatra

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Methods Mentioned

BETA
ubiquitination
protein assay
electrophoresis
PCR
ELISA
bronchoalveolar
lavage
Assay
immunoprecipitation
flow cytometry

Software Mentioned

Graphpad
ImageJ

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