Angelica gigas NAKAI (AG) is a medicinal herb renowned for its historical utilization in traditional medicine, particularly for addressing dyslipidemia, owing to its potent antioxidant properties. The intersection of vascular disease and metabolic abnormalities induced by obesity has prompted scientific inquiry. Researchers affiliated with Jeonbuk National University and Jeonbuk National University Hospital conducted a study to systematically investigate the efficacy of Angelica gigas extract (AGE) in mitigating vascular dysfunction associated with obesity.
The researchers investigated the effects of supplementing 40 high-fat diet (HFD) rats with 100–300 mg/kg/day of AGE. Lee et al. discovered that rats fed with a high-fat diet (HFD) had weakened vascular relaxation responses to acetylcholine. However, administration of AGE successfully restored the impaired relaxation pattern. HFD rats exhibited endothelial dysfunction, which was characterized by increased plaque area, elevated levels of reactive oxygen species, reduced nitric oxide (NO) levels, and diminished phosphorylation of endothelial nitric oxide synthase (eNOS) Ser1177. AGE effectively reversed endothelial dysfunction and its associated biochemical signaling.
Lee and colleagues found that AGE has beneficial effects on endoplasmic reticulum (ER) stress, IRE1α sulfonation, and subsequent sirt1 RNA decay, regulating the IRE1α-dependent decay (RIDD) signaling. This ultimately enhances the availability of NO through the SIRT1-eNOS axis in both the aorta and endothelial cells. Moreover, AGE promotes AMP-activated protein kinase phosphorylation, leading to increased SIRT1 and eNOS deacetylation, further contributing to improved NO availability. Especially, the AGE constituent decision showed similar effects in alleviating endothelial dysfunctions.
The researchers established that AGE effectively governs dyslipidemia-associated vascular dysfunction by regulating ROS-associated ER stress responses, specifically through the IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis. The study outcomes underscore the potential therapeutic value of AGE and advocate for further exploration and consideration in the development of strategies to address cardiovascular issues associated with dyslipidemia.
Reference
Lee GH, Lee HY, Lim YJ, Kim JH, Jung SJ, Jung ES, et al. Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction. Aging. 2023 Dec 13;15(23):13608–27.