Citronellal alleviate macro- and micro-vascular damage in high fat diet / streptozotocin - Induced diabetic rats via a S1P/S1P1 dependent signaling pathway

• Published in: European journal of pharmacology Vol. 920; p. 174796
• Main Authors: Qiu, Yue, Chao, Chun-yan, Jiang, Li, Zhang, Jie, Niu, Qian-qian, Guo, Ya-qi, Song, Yu-ting, Li, Peng, Zhu, Mo-li, Yin, Ya-ling
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.04.2022
• Subjects: Acyclic Monoterpenes; Aldehydes; Animals; Citronellal; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diet, High-Fat - adverse effects; Endothelial dysfunction; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Nitric Oxide Synthase Type III - metabolism; Rats; S1P1; Signal Transduction; Sphingosine 1-phosphate; Streptozocin - adverse effects; Type 2 diabetes mellitus; Citronellal; T2DM; eNOS; Type 2 diabetes mellitus; Sphingosine 1-phosphate; CT; S1P; FTY720; NOx; ROS; Endothelial dysfunction; S1P1; ED
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2022.174796

Citronellal (CT) is an acyclic monoterpene aldehyde isolated from lemon citronella, which could ameliorate vascular endothelial dysfunction in atherosclerosis in our previous study, however, whether CT can alleviate vascular endothelial dysfunction related with type 2 diabetes (T2DM) is still unknown. So, we investigated the role of CT in vascular dysfunction related to T2DM and the mechanism involved. T2DM rat model was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) (60 mg/kg) to rats fed with high-fat diet (HFD) (4 weeks). After treated with CT (150 mg/kg/d), both the thoracic aorta injury and micro-vascular pathological injury in T2DM rats ex vivo were alleviated, and the oxidative stress in T2DM rats treated with CT were attenuated, manifested as increased content of endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD), and decreased content of malondialdehyde (MDA). Furthermore, CT (15 μg/L) increased the migration capacity of human umbilical vein endothelial cells (HUVECs) under high glucose circumstance (30 mM), and increased the endothelial-dependent relaxation in thoracic aorta isolated from T2DM rats in vitro. Finally, all of these effects of CT were blocked by fingolimod (FTY720), a sphingosine-1-phosphate receptor agonist, and the expression of sphingosine-1-phosphate receptor 1 (S1P1) was increased by CT. In conclusion, CT improved vascular function through S1P/S1P1 signaling pathway.