Oridonin, a well-known traditional Chinese herbal medicinal product isolated from Isodon rubescens (Hemsl.) H.Hara, has many potential properties, including anti-inflammatory and
antioxidant activities. However, there is no evidence whether
oridonin have a protective effect on
atherosclerosis. This study focused on the effects of
oridonin on oxidative stress and
inflammation generated from
atherosclerosis. The
therapeutic effect on
atherosclerosis was evaluated by
intraperitoneal injection of
oridonin in a high-fat fed
ApoE-/- mouse model. We isolated mouse peritoneal macrophages and detected the effect of
oridonin on
oxidized low-density lipoprotein-induced
lipid deposition.
Oil red O staining, Masson's staining,
dihydroethidium fluorescence staining, immunohistochemical staining, western blotting analysis, immunofluorescence,
enzyme-linked
immunosorbent assay and quantitative real-time PCR were used to evaluate the effect on
atherosclerosis and explore the mechanisms.
Oridonin treatment significantly alleviated the progression of
atherosclerosis, reduced macrophage infiltration and stabilized plaques.
Oridonin could significantly inhibit
inflammation associated with NLRP3 activation.
Oridonin significantly reduced oxidative stress by blocking Nrf2 ubiquitination and degradation. We also found that
oridonin could prevent the formation of foam cells by increasing
lipid efflux
protein and reducing
lipid uptake
protein in macrophages.
Oridonin has a protective effect on
atherosclerosis in
ApoE-/- mice, which may be related to the inhibition of NLRP3 and the stabilization of Nrf2. Therefore,
oridonin may be a potential therapeutic agent for
atherosclerosis.