Aucubin administration suppresses STING signaling and mitigated high-fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice.

Abstract

The rising obesity epidemic in developed countries is associated with many chronic inflammatory diseases including atherosclerosis and nonalcoholic steatohepatitis (NASH). Consuming aucubin may benefit health by suppressing inflammation. Herein, we studied the effects of aucubin consumption on atherosclerosis and NASH progression induced by high-fat diet (HFD) in LDL receptor deficient (LDLr-/-) mice. Adult LDLr-/- mice were fed with HFD for 12 weeks and received oral administration of aucubin for the last 6 weeks. Aucubin did not alter body weight or dyslipidemia, but lowered hyperglycemia and mitigated HFD-induced atherosclerosis and hepatic impairments in LDLr-/- mice. Aucubin administration inhibited HFD-induced inflammation and downregulated mRNA and protein expression of stimulator of IFN genes (STING) in both aortas and livers of LDLr-/- mice. In vitro, aucubin suppressed mitochondrial DNA (mtDNA)-induced activation of STING/NFκB pathway and downregulated gene expression of pro-inflammatory cytokines in cultured bone marrow-derived macrophages (BMDM). Furthermore, aucubin enhanced microRNA-181a-5p (miR-181a-5p) levels in both aortas and livers of LDLr-/- mice. Importantly, miR-181a-5p mimicked the inhibitory effect of aucubin on STING/NFκB pathway and inflammation in BMDM. In conclusion, aucubin consumption attenuated HFD-induced atherosclerosis and NASH progression in LDLr-/- mice, possibly through modulating miR-181a-5p/STING and inhibiting inflammation.

• Authors: Yu Liu, Yan Zhang, Huanhuan Zhu, Wenzhi Shen, Zheng Chen, Jian Bai, Tian Shuang, Qi Chen
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 169 Pg. 113422 (Nov 2022) ISSN: 1873-6351 [Electronic] England
• PMID: 36108984 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• aucubin
• Cytokines
• DNA, Mitochondrial
• Iridoid Glucosides
• MicroRNAs
• NF-kappa B
• Receptors, LDL
• RNA, Messenger

Topics

• Animals
• Mice
• Atherosclerosis (drug therapy, etiology)
• Cytokines (metabolism)
• Diet, High-Fat (adverse effects)
• DNA, Mitochondrial
• Inflammation (drug therapy)
• Iridoid Glucosides (administration & dosage)
• Mice, Inbred C57BL
• Mice, Knockout
• MicroRNAs (metabolism)
• NF-kappa B (metabolism)
• Non-alcoholic Fatty Liver Disease (drug therapy, etiology)
• Receptors, LDL (genetics)
• RNA, Messenger