Statins have often been used in
atherosclerosis treatment because of its pleiotropic effects on
inflammation. However, some adverse effects of high doses of
statin show reverse effects after withdrawal.
Cyanidin-3-glucoside (C3G) is a powerful anti-
inflammation and
antioxidant that has been of interest for use in combination with low doses of
statin, which may be alternative treatment for
atherosclerosis. The objective is to investigate the synergistic effect of
atorvastatin and C3G in
angiotensin II (Ang II)-induced
inflammation in vascular smooth muscle cells. Human aortic smooth muscle cells (HASMCs) were exposed to Ang II with or without
atorvastatin and C3G alone, or in combination. The results revealed that the combination of
atorvastatin and C3G produces synergism against
inflammation and oxidative stress. The mechanism of the combination of
atorvastatin and C3G suppressed the translocation of the p65 subunit of NF-κB from cytosol to nucleus, and attenuated the expression of
proteins including
inducible nitric oxide synthase, intracellular adhesion molecule 1(ICAM-1), and
vascular cell adhesion molecule 1(VCAM-1), in addition to
nitric oxide (NO) production. Moreover, C3G exerts the antioxidative properties of
atorvastatin through down-regulating NOX1 and promoting the activity of the Nrf2(-)ARE signaling pathway and downstream
proteins including
heme oxygenase (HO-1),
NAD(P)H:quinoneoxidoreductase 1 (NQO-1), and
glutamate-cysteine ligase catalytic subunit (γ-GCLC), besides increasing the activity of
superoxide dismutase (SOD)
enzymes. Taken together, these results suggest that a combination of low dose
statins and C3G might serve as a potential regulator of the
atherosclerosis process which is mediated by attenuating oxidative stress, thereby inhibiting NF-κB and activating Nrf2 signaling pathways induced by Ang II.