Effects of sesquiterpene lactones from Ixeris sonchifolia on bone metabolism and lipid metabolism in ApoE-/-mice
- VernacularTitle:苦碟子倍半萜内酯对ApoE-/-小鼠骨、脂代谢的影响
- Author:
Kui-mao WANG
1
;
Xin PANG
1
;
Jia-hao LYU
1
;
Jian LIU
1
;
Yang HU
1
;
Yu-jie ZHU
1
;
Li-hong HU
1
Author Information
- Publication Type:Journal Article
- Keywords: Ixerin Z; ApoE-/-; bone metabolism; lipid metabolism; PPARα/Wnt/β-Catenin; OPG/RANKL/NF-κB
- From: Chinese Pharmacological Bulletin 2025;41(8):1492-1499
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effects of Ixerin Z,a sesquiterpene lactone from Ixeris sonchifolia,on bone-lipid metabolic imbalance in ApoE-/-mice and to elu-cidate its molecular mechanisms.Methods A mouse model of ApoE-/-was induced using a high-fat diet,followed by eight weeks of Ixerin Z administration at doses of 1 and 10 mg·kg-1.Serum markers related to bone-lipid metabolism and inflammatory cytokines were quantified.Bone mineral density,biomechanical prop-erties,bone tissue morphology,and bone microstructure changes were analyzed.Computational molecular doc-king was performed to identify potential target proteins of Ixerin Z,and its regulatory effects on bone-lipid me-tabolism were investigated.Results Treatment with Ixerin Z markedly decreased the serum levels of total cholesterol,triglycerides,TNF-α,and IL-1β in ApoE-/-mice.It significantly improved bone mineral density,enhanced biomechanical strength,restored tra-becular structure,and reduced fat accumulation in bone tissue.Investigations revealed that Ixerin Z activated PPARα,thereby promoting fatty acid β-oxidation in bone tissue,and stimulating the Wnt/β-Catenin signa-ling pathway to facilitate bone formation.Furthermore,Ixerin Z suppressed the OPG/RANKL/NF-κB signaling pathway,leading to reduced bone resorption,independ-ent of PPARα activation.Conclusions Ixerin Z dem-onstrates potent therapeutic effects on bone-lipid meta-bolic imbalance in ApoE-/-mice.The mechanism in-volves activating PPARα to promote fatty acid β-oxida-tion in bone tissue,activating PPARα/Wnt/β-Catenin signaling pathway to promote bone formation,and in-hibiting OPG/RANKL/NF-κB signaling pathway to re-duce bone resorption.
