Atractylodin, β-eudesmol, and (+)-hinesol in Atractylodes chinensis rhizomes improve glomerular injuries in high immunoglobulin A mice

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Mikio Nishizawa, Toshinari Ishii, Yuto Nishidono, Saki Shirako, Ken Tanaka, Y. Ikeya
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引用次数: 0

Abstract

Background: The rhizome of Atractylodes chinensis (Asteraceae), a crude drug of Japanese Kampo medicines, has been administered to patients with edema, nephrotic syndrome, and gastrointestinal disorders. Essential oils, such as sesquiterpenoids (e.g., β-eudesmol and hinesol) and atractylodin, are rich in the rhizomes. Previously, we discovered that atractylodin, a polyacetylene compound, found in an ethyl acetate (EtOAc)-soluble fraction from a methanol extract of A. chinensis rhizomes, possessed marked anti-inflammatory activities. Oral administration of the EtOAc-soluble fraction reduced immunoglobulin A (IgA) deposition in the renal glomeruli of high immunoglobulin A (HIGA) mice, a model of human IgA nephropathy. An increased serum IgA forms immune complexes and causes the deposition on renal glomeruli, leading to inflammation by the complement-mediated pathway. Objective: The aim of this study is to identify the compounds that reduce IgA deposition in an EtOAc-soluble fraction of A. chinensis rhizomes. Methods: Metabolites in the serum of HIGA and control BALB/c mice were analyzed by gas chromatography–mass spectrometry. A standard diet including each compound was fed to HIGA and BALB/c mice for 20 weeks to evaluate the improvement of glomerular IgA deposition. Results: Metabolomic analysis of serum suggested that the HIGA mice exhibit a state near the early stage of chronic kidney disease, compared with the BALB/c mice. When mice were orally administered each hydrophobic compound of A. chinensis rhizomes, it was revealed that atractylodin, as well as β-eudesmol and (+)-hinesol, efficiently inhibited glomerular IgA deposition. Furthermore, the renal levels of complement component 3 (C3) and proinflammatory cytokine mRNAs were decreased, when the hydrophobic compounds were orally administered to HIGA mice. Conclusion: Atractylodin, β-eudesmol, and (+)-hinesol may inhibit glomerular IgA deposition, probably by attenuating complement-mediated injuries and suppressing proliferation of mesangial cells in the renal glomeruli. These compounds might improve the pathological findings of human IgA nephropathy. Keywords: Atractylodes chinensis; Crude drug; Immunoglobulin A nephropathy; Metabolomics; Complement
白术根茎中的白术素、β-桉叶油醇和(+)-松油醇可改善高免疫球蛋白 A 小鼠的肾小球损伤
背景:白术(菊科)的根茎是日本堪布药的一种粗制药物,曾被用于治疗水肿、肾病综合征和胃肠道疾病患者。白术根茎中含有丰富的精油,如倍半萜(如β-桉叶油醇和松油醇)和白术素。在此之前,我们发现白术素是一种多乙炔化合物,它存在于白术根茎甲醇提取物的乙酸乙酯(EtOAc)可溶部分中,具有明显的抗炎活性。口服乙酸乙酯可溶性馏分可减少高免疫球蛋白 A(HIGA)小鼠(人类 IgA 肾病的模型)肾小球中的免疫球蛋白 A(IgA)沉积。血清中增加的 IgA 会形成免疫复合物并沉积在肾小球上,通过补体介导的途径导致炎症:本研究的目的是在A. chinensis根茎的乙醇萃取物中找出能减少IgA沉积的化合物:方法:采用气相色谱-质谱法分析 HIGA 小鼠和对照组 BALB/c 小鼠血清中的代谢物。给 HIGA 小鼠和 BALB/c 小鼠喂食包括每种化合物在内的标准饮食 20 周,以评估肾小球 IgA 沉积的改善情况:结果:血清代谢组分析表明,与 BALB/c 小鼠相比,HIGA 小鼠表现出接近慢性肾病早期的状态。给小鼠口服白术根茎中的每种疏水化合物,结果发现白术素、β-桉叶油醇和(+)-松油醇能有效抑制肾小球 IgA 沉积。此外,当疏水化合物口服给 HIGA 小鼠时,肾脏中补体成分 3(C3)和促炎细胞因子 mRNA 的水平也有所下降:结论:白术素、β-桉叶油醇和 (+)-hinesol 可抑制肾小球 IgA 沉积,这可能是通过减轻补体介导的损伤和抑制肾小球系膜细胞的增殖实现的。这些化合物可能会改善人类IgA肾病的病理结果:白术;粗药;免疫球蛋白A肾病;代谢组学;补体
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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