连翘酸性多糖的结构特征及抗补体活性研究

S. Shi, Hui Lian, Chao Zhu, Huijun Wang, Ruimin Liu, S. Bligh, Shunchun Wang
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引用次数: 8

摘要

背景:补体系统是宿主抵御外来物质入侵的重要防御机制。然而,过度或不受控制的补体系统激活可能导致严重的补体介导的疾病,对人体有害。目前市场上还没有理想的补体抑制治疗化合物。近年来,由于天然多糖具有一定的免疫调节活性和安全性,其对免疫系统的调节作用已成为研究的热点。本研究从连翘(Forsythia suspensa)中分离得到一种均质酸性多糖Fs-8-ba2(分子量约为7.2 kDa),并对其抗互补作用进行了研究。方法:采用HPGPC、IR、绝对构型、组分分析、甲基化分析、高碘酸盐氧化、羧基还原、部分酸水解、核磁共振等方法对Fs-8-ba2的主要结构特征进行了表征。为了鉴定Fs-8-ba2的抗补体活性,采用体外补体系统经典途径(CP)和替代途径(AP)进行溶血实验。结果:Fs-8-ba2的主链由7个均半乳糖酸(HG)和2个鼠李糖半乳糖酸(RG-I)组成,RG-I的侧链位于1,2,4链α-L-Rha的0 -4位。抗补体实验表明,天然酸性多糖(Fs-8-ba2)通过经典途径(IC50: 0.311±0.020 mg/mL vs. 3.292±0.032 mg/mL)和替代途径(IC50: 0.218±0.015 mg/mL vs.无活性)对补体活化的抑制作用强于羧基还原多糖(Fs-8-ba2re)。说明果胶多糖的抗补体作用与GalA(羧基)含量有关。利用补体缺失血清进行的初步机制研究表明,Fs-8-ba2选择性地与C1q、C1r、C1s、C2、C3和C9相互作用,而不与C4和C5相互作用。结论:酸性多糖Fs-8-ba2可能对补体介导的疾病有潜在的治疗作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Structural Features and Anti-Complement Activity of an Acidic Polysaccharide from Forsythia suspensa
Background: The complement system is an important host defence mechanism against the invasion of foreign materials. However, excessive or uncontrolled activation of the complement system might lead to severe complement-mediated disorders which are harmful to human bodies. There are still no desirable therapeutic compounds available on the market for complement inhibition. In recent years, researches have been focused on natural polysaccharides to modulate of the immune system because of their immunomodulatory activities and safety. In this study, Fs-8-ba2, a homogeneous acidic polysaccharide (MW ca. 7.2 kDa) was isolated from Forsythia suspensa and its anti-complementary effect was investigated. Method: The major primary structural features of Fs-8-ba2 were elucidated using HPGPC, IR, absolute configuration, component analysis and methylation analysis, periodate oxidation, carboxyl reduction partial acid hydrolysis, and NMR spectroscopy, etc. To identify the anti-complementary activity of Fs-8-ba2, the hemolytic assays through the classical pathway (CP) and the alternative pathway (AP) of complement system in vitro were taken. Results: The backbone of Fs-8-ba2 was composed of 7 homogalacturonan (HG) and 2 rhamnogalacturonan (RG-I) moieties with the side chains attached at O-4 of 1,2,4-linked α-L-Rha in the RG-I moieties. The anti-complement assay showed that the native acidic polysaccharide (Fs-8-ba2) possessed stronger inhibitory effect on the complement activation than the carboxyl-reduced polysaccharide (Fs-8-ba2re) through the classical (IC50: 0.311 ± 0.020 mg/mL vs. 3.292 ± 0.032 mg/mL) and alternative pathways (IC50: 0.218 ± 0.015 mg/mL vs. no activity). It indicated that the anti-complement effect of pectic polysaccharide was related to GalA content (carboxyl group). Preliminary mechanism studies by using complement-depleted sera indicated that Fs-8-ba2 selectively interacted with C1q, C1r, C1s, C2, C3 and C9, but not C4 and C5. Conclusion: These results suggested that Fs-8-ba2, an acidic polysaccharide, could be of potential benefits in the treatment of the complement-mediated diseases.
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