Open AccessAlpha‐mangostin improves endothelial dysfunction in db/db mice through inhibition of aSMase/ceramide pathway
Author(s) -
Jiang Meng,
Huang Shanya,
Duan Wang,
Liu Qiaoshu,
Lei Minxiang
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16456
Subject(s) - ceramide , enos , endocrinology , endothelium , medicine , endothelial dysfunction , biology , apoptosis , chemistry , nitric oxide , biochemistry , nitric oxide synthase
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.