Drug Design, Development and Therapy (May 2024)
Notoginsenoside R1 Ameliorate High-Fat-Diet and Vitamin D3-Induced Atherosclerosis via Alleviating Inflammatory Response, Inhibiting Endothelial Dysfunction, and Regulating Gut Microbiota
Abstract
Liying Ma,1,2 Yansong Gao,1 Ge Yang,1 Lei Zhao,2 Zijian Zhao,1 Yujuan Zhao,1 Yuhang Zhang,2 Shenhui Li,2 Shengyu Li1 1Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun, 130033, People’s Republic of China; 2School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of ChinaCorrespondence: Shengyu Li, Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), No. 1363 Sheng-Tai Street, Changchun, Jilin Province, 130033, People’s Republic of China, Tel +86 431 87063289, Fax +86 431 87063075, Email [email protected]: The inflammatory response plays a pivotal role in the occurrence, progression, and plaque formation of atherosclerosis. The study was performed to investigate the impacts of notoginsenoside R1 on the development of atherosclerosis (AS) and the potential mechanisms.Methods: Rats induced with AS by a high-fat-diet and vitamin D3 were treated with notoginsenoside R1 for six weeks. The ameliorative effect of NR1 on AS rats was assessed by detecting pathological changes in the abdominal aorta, biochemical indices in serum and protein expression in the abdominal aorta, as well as by analysing the gut microbiota.Results: The NR1 group exhibited a noticeable reduction in plaque pathology. Notoginsenoside R1 can significantly improve serum lipid profiles, encompassing TG, TC, LDL, ox-LDL, and HDL. Simultaneously, IL-6, IL-33, TNF-α, and IL-1β levels are decreased by notoginsenoside R1 in lowering inflammatory elements. Notoginsenoside R1 can suppress the secretion of VCAM-1 and ICAM-1, as well as enhance the levels of plasma NO and eNOS. Furthermore, notoginsenoside R1 inhibits the NLRP3/Cleaved Caspase-1/IL-1β inflammatory pathway and reduces the expression of the JNK2/P38 MAPK/VEGF endothelial damage pathway. Fecal analysis showed that notoginsenoside R1 remodeled the gut microbiota of AS rats by decreasing the count of pathogenic bacteria (such as Firmicutes and Proteobacteria) and increasing the quantity of probiotic bacteria (such as Bacteroidetes).Conclusion: Notoginsenoside R1, due to its unique anti-inflammatory properties, may potentially prevent the progression of atherosclerosis. This mechanism helps protect the vascular endothelium from damage, while also regulating the imbalance of intestinal microbiota, thereby maintaining the overall health of the body. Keywords: notoginsenoside R1, inflammation, endothelial damage, gut microbiota
