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白术属五种药用植物对类风湿性关节炎大鼠的药效学和代谢组学研究。

Study on the pharmacodynamics and metabolomics of five medicinal species in Atractylodes DC. on rats with rheumatoid arthritis.

作者信息

Liu Yuqiang, Zhang Beixue, Cai Qian

机构信息

Department of Medicine, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.

Department of Medicine, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.

出版信息

Biomed Pharmacother. 2020 Nov;131:110554. doi: 10.1016/j.biopha.2020.110554. Epub 2020 Sep 2.

DOI:10.1016/j.biopha.2020.110554
PMID:32890964
Abstract

Atractylodes DC. mainly includes Atractylodis Rhizoma and Atractylodis macrocephalae Rhizoma. According to Chinese Pharmacopoeia, Atractylodis Rhizoma is the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) and Atractylodes chinensis (DC.) Koidz. (A. chinensis), while Atractylodis macrocephalae Rhizoma is the rhizome of Atractylodes macrocephala Koidz. (A. macrocephala). Although Atractylodes japonica Koidz. ex Kitam. (A. japonica) and Atractylodes coreana (Nakai) Kitam. (A. coreana) are not included in the Pharmacopoeia, they are often used as Atractylodis Rhizoma in northern China. But in Japan, A. japonica is used as Atractylodis macrocephalae Rhizoma. In order to compare the efficacy of A. japonica and A. coreana with that of Atractylodis Rhizoma and Atractylodis macrocephalae Rhizomain in Pharmacopoeia, this paper studies the anti rheumatism of the five medicinal species in Atractylodes DC., and provides the basis for the rational application of A. japonica and A. coreana. With this purpose, the rheumatoid model of rats was established by Freund's complete adjuvant. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF - α), arthritis factor (RF), anti cyclic citrullinated peptide (anti-CCP), interleukin-1β (IL-1β), Nuclear factor-κB (NF - κB), interleukin-10 (IL-10) and Prostaglandin E2 (PGE2) in rats of each group. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to analyze the plasma of each group. After that, multivariate statistical analysis method was used to analyze the data. The results showed that the five medicinal species in Atractylodes DC. can reduce the levels of IL-6, IL-1 β, PGE2 and NF - κB in the plasma of rheumatoid arthritis (RA) rats in varying degrees, among which the regulation of A. macrocephala is relatively weak. A. chinensis, A. lancea, A. coreana and A. japonica can significantly reduce the content of TNF - α, in which A. japonica and A. lancea have better and similar regulatory effects. A. chinensis and A. coreana can significantly reduce the content of RF in arthritis rats. A. coreana, A. lancea and A. japonica can significantly reduce the anti-CCP level, that is, the regulatory effect of A. coreana and A. chinensis is similar. The metabolic disorder of 11-deoxycortisol, taurocholate and other small molecules in the body of rats with RA directly affects the metabolic pathways of primary bile acid biosynthesis and steroid hormone biosynthesis, leading to the decline of immune function and other symptoms. Most of the metabolic pathways tend to be normal after oral administration of five medicinal species in Atractylodes DC. Among them, the regulating effect of A. coreana and A. chinensis is similar, while that of A. japonica and A. lancea are similar. A. macrocephala had little effect of intervention.

摘要

白术属植物主要包括白术和苍术。根据《中国药典》,白术为菊科植物白术Atractylodes macrocephala Koidz.的干燥根茎,而苍术为菊科植物茅苍术Atractylodes lancea (Thunb.) DC.和北苍术Atractylodes chinensis (DC.) Koidz.的干燥根茎。虽然关苍术Atractylodes japonica Koidz. ex Kitam.和朝鲜苍术Atractylodes coreana (Nakai) Kitam.未被《中国药典》收载,但在中国北方常被用作苍术。而在日本,关苍术被用作白术。为比较关苍术和朝鲜苍术与《中国药典》中白术和苍术的功效,本文研究了白术属5种药用植物的抗风湿作用,为关苍术和朝鲜苍术的合理应用提供依据。为此,采用弗氏完全佐剂建立大鼠类风湿性关节炎模型。然后,采用酶联免疫吸附测定(ELISA)法测定各组大鼠血浆中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、类风湿因子(RF)、抗环瓜氨酸肽(抗CCP)、白细胞介素-1β(IL-1β)、核因子-κB(NF-κB)、白细胞介素-10(IL-10)和前列腺素E2(PGE2)的含量。采用超高效液相色谱-四极杆飞行时间质谱联用(UHPLC-Q-TOF-MS)法分析各组大鼠血浆。之后,采用多元统计分析方法对数据进行分析。结果表明,白术属5种药用植物均能不同程度降低类风湿性关节炎(RA)大鼠血浆中IL-6、IL-1β、PGE2和NF-κB水平,其中白术的调节作用相对较弱。茅苍术、北苍术、朝鲜苍术和关苍术均能显著降低TNF-α含量,其中关苍术和茅苍术调节作用较好且相近。北苍术和朝鲜苍术能显著降低关节炎大鼠RF含量。朝鲜苍术、茅苍术和关苍术均能显著降低抗CCP水平,即朝鲜苍术和北苍术调节作用相近。RA大鼠体内11-脱氧皮质醇、牛磺胆酸盐等小分子代谢紊乱直接影响初级胆汁酸生物合成和类固醇激素生物合成代谢途径,导致免疫功能下降等症状。白术属5种药用植物灌胃给药后,大部分代谢途径趋于正常。其中,朝鲜苍术和北苍术调节作用相近,关苍术和茅苍术调节作用相近。白术干预作用较小。

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