Dataset Information

Dihydroartemisinin modulated arachidonic acid metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

ABSTRACT:

Background

Dihydroartemisinin (DHA), a derivative of Artemisia annua, has been shown to possess anti-inflammatory properties. Besides, Yes-associated protein 1 (YAP1) plays a crucial role in maintaining liver homeostasis.

Methods

This study used Yap1 ^Flox/Flox, Albumin-Cre mice with hepatocyte-specific Yap1 knockout (referred to as Yap1 ^LKO) and their control mice (Yap1 ^Flox/Flox, referred to as Yap1 ^Flox). The effect of Yap1 on lipid metabolism homeostasis was investigated through non-targeted metabolomic analysis of mouse liver. Subsequently, DHA was administered to Yap1 ^LKO mice to assess its potential as a treatment. Liver pathology was evaluated via H&E staining, and the levels of AST, ALT, and TG were quantified using biochemical assays. The contents of arachidonic acid (AA), prostaglandin E1 (PGE1), and leukotrienes (LT) in the liver were measured using ELISA, while the protein expressions of PLIN2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2) were analyzed through IHC staining.

Results

Hepatocyte-specific Yap1 knockout activated the AA metabolic pathway, resulting in increased elevated levels of AA, PGE1, and LT levels, along with inflammatory cytokine infiltration. DHA mitigated the elevation of metabolites such as PGE1 and LT caused by the AA metabolic pathway activation by down-regulating the levels of COX-2 and 5-LOX in the liver of Yap1 ^LKO mice. Moreover, it alleviated the accumulation of lipid vacuoles and reduced triglyceride (TG) and perilipin-2 (PLIN2) levels in the liver of Yap1 ^LKO mice.

Conclusions

Excessively low YAP1 expression induces liver inflammation and disturbances in lipid metabolism, whereas DHA modulated AA metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

SUBMITTER: Xue Y

PROVIDER: S-EPMC11255665 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Dihydroartemisinin modulated arachidonic acid metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

Xue Yu Y Lu Junlan J Liu Yiwei Y Gao Yuting Y Gong Yi Y Yang Yanguang Y Xiong Yajun Y Shi Xinli X

Heliyon 20240623 13

<h4>Background</h4>Dihydroartemisinin (DHA), a derivative of Artemisia annua, has been shown to possess anti-inflammatory properties. Besides, Yes-associated protein 1 (YAP1) plays a crucial role in maintaining liver homeostasis.<h4>Methods</h4>This study used <i>Yap1</i> <sup>Flox/Flox</sup>, Albumin-Cre mice with hepatocyte-specific <i>Yap1</i> knockout (referred to as <i>Yap1</i> <sup>LKO</sup>) and their control mice (<i>Yap1</i> <sup>Flox/Flox</sup>, referred to as <i>Yap1</i> <sup>Flox</su ...[more]

PMID: 39027511

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Dataset Information

Dihydroartemisinin modulated arachidonic acid metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

Background

Methods

Results

Conclusions

Publications

Dihydroartemisinin modulated arachidonic acid metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.

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