Comparative effect of berberine and its derivative 8-cetylberberine on attenuating atherosclerosis in ApoE-/- mice

Berberine (BBR), one of the main bioactive compounds in Rhizoma coptidis, has multiple pharmacological activities. It has been reported that 8-cetylberberine (8-BBR-C16) has increased anti-microbial property in vivo and a higher bioavailability in hamsters. Therefore, in the present study, we used apolipoprotein E-deficient mice (ApoE(-/-)) as an atherosclerosis model to investigate the anti-atherosclerosis effects of 8-BBR-C16. After 12 weeks of treatment, the atherosclerotic plaque area of the aorta, serum lipid profile, the plasma redox state and the expression of inflammatory cytokines in ApoE(-/-) mice were determined. Both BBR and 8-BBR-C16 significantly decreased the atherosclerotic plaque area by suppressing inflammatory and oxidative markers in ApoE(-/-) mice. Treatment with BBR or 8-BBR-C16, decreased serum levels of IL-1 beta and TNF-alpha as well as mRNA levels of NF-kappa Bp65, i-NOS, ICAM-1, IL-6 in the aorta. In addition, the expression of NF-kappa B p65 protein decreased in the nucleus, whereas I kappa B alpha levels increased in the cytosol. The anti-inflammatory and anti-oxidative effect of BBR and 8-BBR-C16 attributed to inhibition of the translocation of NF-kappa B to the nucleus. Since the dosage of BBR used was 10 fold higher than that of 8-cetylberberine, we conclude that 8-BBR-C16 is more efficient in treating atherosclerosis in ApoE(-/-) mice. (C) 2016 Published by Elsevier B.V.