Inhibitory effects of cycloastragenol on abdominal aortic aneurysm and its related mechanisms.

ABSTRACT:

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. However, whether CAG can protect against AAA remains elusive. In this study, we investigated whether CAG has an inhibitory effect on AAA and its related mechanism.

Experimental approach

The AAA mouse model was induced by incubating the abdominal aorta with elastase. CAG was administered by gavage at different doses beginning on the same day or 14 days after inducing AAA to explore its preventive or therapeutic effects respectively. The preventive effects of CAG on AAA were verified in 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 TNF-?.

Key results

Compared to the control AAA model group, CAG (125 mg·kg^-1 body weight day^-1 ) reduced the incidence of AAA, the dilatation of aorta and elastin degradation in media in both mouse models of AAA. CAG suppressed the inflammation, oxidation, phenotype switch and apoptosis in TNF-?-stimulated VSMCs, ameliorated the expression and activity of MMPs and decreased the activation of the ERK/JNK signalling pathway. CAG also inhibited the degradation of elastin in TNF-?-stimulated VSMCs.

Conclusion and implications

CAG presents protective effects against AAA through down-regulation of the MAPK signalling pathways and thus attenuates inflammation, oxidation, VSMC phenotype switch and apoptosis and the expression of MMPs as well as increasing elastin biosynthesis.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6295405 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature