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Planta Med 2022; 88(11): 899-912
DOI: 10.1055/a-1659-3908
Biological and Pharmacological Activity
Original Papers

Rosmarinic Acid Suppresses Abdominal Aortic Aneurysm Progression in Apolipoprotein E-deficient Mice

Huimiao Bian‡
1   Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang, China
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Yang Wang‡
3   West Yunnan University of Applied Sciences, Jinghong, Yunnan, China
4   Metabo-Profile Biotechnology (Shanghai) Co. Ltd., Shanghai, China
,
Peng Wu
1   Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang, China
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Na Han
1   Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang, China
,
Linlin Wang
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Xue Li
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
XianJing Zhang
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Kenka Cho
5   Takarazuka University of Medical and Health Care, Hanayashiki-Midorigaoka, Takarazuka-city, Japan
,
Yongyu Zhang
3   West Yunnan University of Applied Sciences, Jinghong, Yunnan, China
,
Jun Yin
1   Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang, China
,
Baohong Jiang
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
› Author Affiliations
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Abstract

An abdominal aortic aneurysm is a life-threatening cardiovascular disorder caused by dissection and rupture. No effective medicine is currently available for the > 90% of patients whose aneurysms are below the surgical threshold. The present study investigated the impact of rosmarinic acid, salvianolic acid C, or salvianolic acid B on experimental abdominal aortic aneurysms. Abdominal aortic aneurysms were induced in apolipoprotein E-deficient mice via infusion of angiotensin II for 4 wks. Rosmarinic acid, salvianolic acid C, salvianolic acid B, or doxycycline as a positive control was provided daily through intraperitoneal injection. Administration of rosmarinic acid was found to decrease the thickness of the aortic wall, as determined by histopathological assay. Rosmarinic acid also exhibited protection against elastin fragmentation in aortic media and down-regulated cell apoptosis and proliferation in the aortic adventitia. Infiltration of macrophages, T lymphocytes, and neutrophils in aortic aneurysms was found, especially at the aortic adventitia. Rosmarinic acid, salvianolic acid C, or salvianolic acid B inhibited the infiltration on macrophages specifically, but these compounds did not influence T lymphocytes and neutrophils. Expression of matrix metalloproteinase 9 and macrophage migration inhibitory factor significantly increased in aortic aneurysms. Rosmarinic acid and salvianolic acid C decreased the expression of matrix metalloproteinase-9 in media, and rosmarinic acid also tended to reduce migration inhibitory factor expression. Further then, partial least squares-discriminate analysis was used to classify metabolic changes among different treatments. Rosmarinic acid affected most of the metabolites in the biosynthesis of the citrate cycle, fatty acid pathway significantly. Our present study on mice demonstrated that rosmarinic acid inhibited multiple pathological processes, which were the key features important in abdominal aortic aneurysm formation. Further study on rosmarinic acid, the novel candidate for aneurysmal therapy, should be undertaken to determine its potential for clinical use.

Key words

abdominal aortic aneurysm - rosmarinic acid - salvianolic acid C - salvianolic acid B - Salvia miltiorrhiza Bunge - Labiatae

Supporting Information

    This section consists of structure identification for RA, SalC, and SalB and the interaction of RA, SalC, and SalB with MMP-9. The images of H&E staining for each mice and experimental protocol were shown. The table indicates the affected pathways of the model group.

  • Supporting Information


Publication History

Received: 02 April 2021

Accepted after revision: 17 September 2021

Article published online:
05 November 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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