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Alpha-mangostin improves endothelial dysfunction in db/db mice through inhibition of aSMase/ceramide pathway |
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| Authors: | Meng Jiang Shanya Huang Wang Duan Qiaoshu Liu Minxiang Lei |
| Affiliation: | 1. Xiangya Hospital of Central South University, Changsha, China Contribution: Data curation (equal), Formal analysis (equal), Investigation (lead), Methodology (equal), Software (equal), Validation (equal), Visualization (equal), Writing - original draft (lead);2. Xiangya Hospital of Central South University, Changsha, China Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Software (equal), Writing - original draft (equal);3. Xiangya Hospital of Central South University, Changsha, China Contribution: Data curation (equal), Investigation (equal), Methodology (equal), Software (equal);4. Xiangya Hospital of Central South University, Changsha, China |
| Abstract: | Diabetic vascular complications are the leading causes of death and disability in patients with diabetes. Alpha-mangostin has been reported to have anti-diabetic capacity in recent years. Here, we investigated the protective function of alpha-mangostin on endothelium in vitro and in vivo experiments. We also observed that alpha-mangostin improved impaired endothelium-dependent vasodilation (EDV) of diabetic animals while it limited the aSMase/ceramide pathway and up-regulated eNOS/NO pathway in aortas from diabetic mice. Meanwhile, alpha-mangostin inhibited elevated aSMase/ceramide pathway and reversed impaired EDV induced by high glucose in isolated mouse aortas. In addition, alpha-mangostin increased phosphorylation of eNOS and NO production in high glucose-treated aortas. Alpha-mangostin normalized high glucose-induced activation of aSMase/ceramide pathway and improved eNOS/NO pathway in endothelial cells with high glucose. In conclusion, alpha-mangostin regulates eNOS/NO pathway and improves EDV in aortas of diabetic mice through inhibiting aSMase activity and endogenous ceramide accumulation. |
| Keywords: | acid sphingomyelinase alpha-mangostin ceramide diabetes |