Comparative effect of berberine and its derivative 8-cetylberberine on attenuating atherosclerosis in ApoE-/- mice
Comparative effect of berberine and its derivative 8-cetylberberine on attenuating atherosclerosis in ApoE-/- mice
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DOI：
10.1016/j.intimp.2016.12.001
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发表时间：
2017-02-01
影响因子：
5.6
通讯作者：
Ye, Xiaoli
中科院分区：
文献类型：
--
作者：
Feng, Min;Zou, Zongyao;Ye, Xiaoli
小檗碱是黄连中的主要活性成分之一，具有多种药理活性。据报道，8-十六烷基小檗碱（8-BBR-C16）具有增强的体内抗菌性能和较高的仓鼠生物利用度。因此，在本研究中，我们使用载脂蛋白E缺陷小鼠（ApoE（-/-））作为动脉粥样硬化模型，以研究8-BBR-C16的抗动脉粥样硬化作用。给药12周后，测定ApoE（-/-）小鼠主动脉粥样硬化斑块面积、血脂、血浆氧化还原状态和炎性细胞因子的表达。BBR和8-BBR-C16均通过抑制ApoE（-/-）小鼠的炎症和氧化标志物显著降低动脉粥样硬化斑块面积。用BBR或8-BBR-C16处理，降低血清IL-1 β和TNF-α水平以及主动脉中NF-κ Bp 65、i-NOS、ICAM-1、IL-6的mRNA水平。此外，NF-κ B p65蛋白在细胞核中的表达降低，而I κ B α在细胞质中的水平升高。BBR和8-BBR-C16的抗炎和抗氧化作用归因于抑制NF-κ B向核的移位。由于BBR的使用剂量比8-十六烷基小檗碱高10倍，因此我们得出结论，8-BBR-C16在治疗ApoE（-/-）小鼠的动脉粥样硬化中更有效。(C)2016由Elsevier B. V.出版
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.