

A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 15, Issue 23, entitled, “Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.”
Because of its antioxidant action, Angelica gigas NAKAI (AG) is a popular traditional medicinal herb frequently used to treat dyslipidemia. Obesity-induced metabolic syndrome is intricately linked to vascular disease, and AG extract (AGE) has therapeutic effects on obesity-associated vascular dysfunction. However, the efficacy of AGE against obesity and its underlying processes have yet to be thoroughly studied. Researchers from Jeonbuk National University and Jeonbuk National University Hospital supplemented 40 high fat diet (HFD) rats with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction.
“The primary aim of this study is to examine the inhibitory effects of AGE on dyslipidemia-associated vascular disease, with a focus on its potential mechanisms of action.”
HFD rats’ vascular relaxation responses to acetylcholine were reduced, while AGE treatment restored the altered relaxation pattern. Endothelial dysfunction was observed in HFD rats, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated ER stress and IRE1 sulfonation, as well as subsequent sirt1 RNA decay, by modulating regulated IRE1-dependent decay (RIDD) signaling, ultimately boosting NO bioavailability via the SIRT1-eNOS axis in aortic and endothelial cells.
Independently, AGE increased AMPK phosphorylation, as well as SIRT1 and eNOS deacetylation and NO bioavailability. Decursin, an important component of AGE, has a similar effect on endothelial dysfunction. These findings show that AGE controls ROS-associated ER stress responses, including IRE1-RIDD/sirt1 degradation and the AMPK-SIRT1 axis, to regulate dyslipidemia-associated vascular dysfunction.
“Ultimately, this study presents evidence that AGE is a promising natural product-based functional food/herbal medicine candidate for preventing or regulating hyperlipidemic cardiovascular complications.”
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