Targeting PPARα/γ by icariside II to rescue GalN/LPS-induced acute liver injury in mice: Involvement of SIRT6/NF-κB signaling pathway.

Autor: Gong MX; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China., Wei JJ; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China., Yi Y; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China., Liu X; Liaoning University of Traditional Chinese Medicine, Shenyang 110847, PR China., Hou FQ; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China., Li YQ; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China., Zhang YD; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China., Gong QH; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China., Li HB; Liaoning University of Traditional Chinese Medicine, Shenyang 110847, PR China. Electronic address: lhb-zyxy@lnutcm.edu.cn., Gao JM; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, PR China; Department of Pharmacology, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, PR China; Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou, PR China. Electronic address: gaojianmei@zmu.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Nov 16; Vol. 136, pp. 156250. Date of Electronic Publication: 2024 Nov 16.
DOI: 10.1016/j.phymed.2024.156250
Abstrakt: Background: Peroxisome proliferator-activated receptor α and-γ (PPARα/γ) are known to play crucial roles in acute liver injury (ALI). Icariside II (ICS II), a natural flavonoid compound derived from Herba EpimedII, confers neuroprotection with PPARα/γ induction potency.
Purpose: This study was aimed to explore whether ICS II has the capacity to protect against ALI, and the role of PPARα/γ in the beneficial effect of ICS II on ALI.
Methods: Mice challenged by D-galactosamine (GalN)/lipopolysaccharide (LPS) and Kupffer cells (KCs) upon LPS insult were used as ALI models in vivo and in vitro. PPARα/γ-deficient mice were treated with ICS II to validate the potential targets of ICS II on ALI.
Results: We found that ICS II (5, 10, 20 mg/kg) dose-dependently improved the survival rate and liver histology, decreased ALT and AST in GalN/LPS-treated mice. Furthermore, ICS II directly bound to PPARα/γ and increased their activities. The protective properties of ICS II were counteracted when PPARα/γ were knocked out in GalN/LPS-induced mice and LPS-induced KCs, respectively. Mechanistically, ICS II restored mitochondrial function, reduced oxidative stress and inflammation through activating PPARα/γ, which activated Sirt6 and inhibited NF-κB nuclear translocation.
Conclusion: Our findings not only highlight PPARα/γ-SIRT6 signaling as a vital therapeutic target to combat ALI, but also reveal ICS II may serve as a novel dual PPARα/γ agonist to safeguard ALI from the oxidation-inflammation vicious circle by mediating SIRT6/NF-κB.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: