Angelica gigas Extract Inhibits Acetylation of eNOS in Vascular Dysfunction


“Angelica gigas Nakai (AG), a traditional medicinal herb, is garnering scientific attention for its potential in addressing a variety of health conditions.” 

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BUFFALO, NY- December 27, 2023 – 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.”

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this new study, researchers Geum-Hwa Lee, Hwa-Young Lee, Young-Je Lim, Ji-Hyun Kim, Su-Jin Jung, Eun-Soo Jung, Soo-Wan Chae, Juwon Lee, Junghyun Lim, Mohammad Mamun Ur Rashid, Kyung Hyun Min, and Han-Jung Chae 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 dysfunction, with a focus on its potential mechanisms of action.”

The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells.

Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

“Ultimately, this study presents clearly 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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Corresponding Authors: Kyung Hyun Min, Han-Jung Chae

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Keywords: Angelica gigas, decursin, IRE1α, sulfonation, RIDD, SIRT1, vascular dysfunction

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About Aging-US:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed CentralWeb of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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