n/a The Chinese University of Hong Kong Hong Kong, Hong Kong
Disclosure(s):
Lin Wang: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Diabetes mellitus results in endothelial dysfunction, while endothelial dysfunction is linked to the majority of cardiovascular diseases. This project aimed to: (1)investigate whether isoliquiritigenin (ISL), which was extracted from traditional Chinese medicine Licorice, could improve vascular function in type Ⅱ diabetic mice; (2)investigate the underlying mechanism of ISL’s protective effect on vascular function in type Ⅱ diabetic mice.
Methods: Animal experiments were performed on male type Ⅱ diabetic db/db mice and the counterpart heterozygote db/m+ mice. Both db/db mice and db/m+ mice were randomly divided into 2 groups. At 8 weeks of age, the db/db and db/m+ mice were treated with 20 mg/kg body weight/day ISL or vehicle (PBS) via oral gavage for 8 weeks. After euthanasia, mouse aorta were collected for further analysis.
Results: The endothelium-dependent relaxation (EDR) induced by the addition of acetylcholine (ACh) was impaired in the db/db control mouse compared to the db/m+ counterparts. After 8-week oral gavage treatment, the ISL treatment group showed improved EDR in db/db mice aortae, while did not show significant effect in db/m+ mouse aortae. The total endothelium-independent relaxation induced by sodium nitroprusside (SNP) was found comparable among all groups. ROS levels were increased in db/db mouse aortic rings as compared to db/m+ and were lowered by ISL. What’s more, pro-inflammatory cytokines TNF-α, MCP-1, IL-6 were up-regulated while the anti-inflammatory cytokine IL-10 was down-regulated in db/db mouse aortae, and ISL could rescue such effects. Besides, the expression level of NOX2 and iNOS, which were 2 important source of ROS, were found to be up-regulated in db/db mouse aortae and were reduced by ISL. The antioxidant genes SOD-1, SOD-2 and SOD-3 were found to be down-regulated in db/db mouse aortae and were increased by ISL. In addition, the nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1), were also found to be down-regulated in db/db control mouse aortae and were increased by ISL.
Conclusions: Isoliquiritigenin could alleviate endothelial dysfunction via attenuating inflammation and oxidative stress in type Ⅱ diabetes, which was possibly through regulating Nrf2/HO-1 signaling pathway.
Funding Sources: State Key Laboratory of Agrobiotechnology (The Chinese University of Hong Kong)
