Inhibitory Effects of Cycloastragenol on Abdominal Aortic Aneurysm and its Related Mechanisms.

BACKGROUND AND PURPOSE: Abdominal aortic aneurysm (AAA) is a degenerative disease affecting human health. But there are no safe and effective medications for AAA therapy. Cycloastragenol (CAG), derived from Astragali Radix, has various pharmacological effects. But whether CAG can protect against AAA remains elusive. This study aims to investigate whether CAG has inhibitory effect on AAA and it's related mechanism.

EXPERIMENTAL APPROACH: AAA mouse model was induced by incubating abdominal aorta of mice with elastase. CAG at different doses was administrated by gavage beginning on the same day on or 14 days after AAA inducement to explore its preventive or therapeutic effects, respectively. And the preventive effects of CAG on AAA were also verified by another AAA mouse model induced by Angiotensin II in ApoE-/- mouse. In vitro experiments were implemented on rat vascular smooth muscle cells (VSMCs) stimulated by tumor necrosis factor α.

KEY RESULTS: Compared to AAA model group, CAG (125 mg·kg-1 body weight per day) reduced the incidence of AAA, the dilatation of aorta and elastin degradation in media in both AAA mouse model induced by either elastase or angiotensin II. CAG treatment suppressed inflammation, oxidation, VSMCs phenotype switch and apoptosis, ameliorated the expression and activity of MMPs, as well as decreased activation of ERK/JNK signaling pathway, CAG could also facilitate elastin biosynthesis.

CONCLUSION AND IMPLICATIONS: CAG presents protective effects against AAA through down-regulation of MAPKs signaling pathways, and thus attenuation of inflammation, oxidation, VSMC phenotype switch and apoptosis and MMPs expression as well as increase of elastin biosynthesis.