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乌头碱:一种治疗系统性红斑狼疮的潜在新疗法。

Aconitine: A potential novel treatment for systemic lupus erythematosus.

作者信息

Li Xiaodong, Gu Liwei, Yang Lan, Zhang Dong, Shen Jianying

机构信息

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

出版信息

J Pharmacol Sci. 2017 Mar;133(3):115-121. doi: 10.1016/j.jphs.2017.01.007. Epub 2017 Feb 24.

Abstract

BACKGROUND

Aconitum plants have been widely used in China for thousands of years. Recent evidences indicate that aconitine, the main active ingredient of Aconitum, has immunomodulatory properties that might be useful for treating autoimmune diseases, such as rheumatoid arthritis. In this study, we conducted a pilot study to explore the effect and mechanisms of aconitine on the treatment of systemic lupus erythematosus.

METHODS

A pristane-induced murine model was used. The pristane-induced mice were treated with aconitine (25, 75 μg kg d, po) for 9 weeks. Every three weeks, proteinuria was detected to monitor the kidney damage and blood was collected to measure serum levels of autoantibodies, besides the kidney pathological examination. The major B cell activating factor and major pro-inflammatory mediators, PGE2, IL-17a and IL-6, were also detected.

RESULTS

We found that aconitine significantly improved the mouse health, decreased the elevated blood leukocyte counts, reduced the serum level of anti-double-stranded DNA (anti-dsDNA) antibody, greatly ameliorated renal histopathologic damage and reduced IgG deposit in glomerular. Furtherly, the levels of PGE2, IL-17a and IL-6, were found to have decreased in aconitine treated mice.

CONCLUSION

We have demonstrated that aconitine can inhibit the progression of disease and ameliorate the pathologic lesion of systemic lupus erythematosus.

摘要

背景

乌头属植物在中国已被广泛使用了数千年。最近的证据表明,乌头属植物的主要活性成分乌头碱具有免疫调节特性,可能对治疗自身免疫性疾病,如类风湿性关节炎有用。在本研究中,我们进行了一项初步研究,以探讨乌头碱治疗系统性红斑狼疮的效果和机制。

方法

使用了一种由降植烷诱导的小鼠模型。用乌头碱(25、75μg/kg·d,口服)对降植烷诱导的小鼠进行9周治疗。除了肾脏病理检查外,每三周检测一次蛋白尿以监测肾脏损伤,并采集血液以测量血清自身抗体水平。还检测了主要的B细胞活化因子和主要的促炎介质PGE2、IL-17a和IL-6。

结果

我们发现乌头碱显著改善了小鼠健康状况,降低了升高的白细胞计数,降低了抗双链DNA(抗dsDNA)抗体的血清水平,大大改善了肾脏组织病理学损伤,并减少了肾小球中的IgG沉积。此外,在乌头碱治疗的小鼠中发现PGE2、IL-17a和IL-6的水平降低。

结论

我们已经证明乌头碱可以抑制系统性红斑狼疮的疾病进展并改善其病理病变。

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