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基于代谢组学的当归不同炮制品多糖保肝作用研究

Metabonomics study on the hepatoprotective effect of polysaccharides from different preparations of Angelica sinensis.

机构信息

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province 730070, China.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province 730070, China.

出版信息

J Ethnopharmacol. 2014 Feb 12;151(3):1090-1099. doi: 10.1016/j.jep.2013.12.011. Epub 2013 Dec 27.

DOI:10.1016/j.jep.2013.12.011
PMID:24378353
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Angelica sinensis (AS) has been used for thousands of years in Traditional Chinese Medicine (TCM). Processed products of AS mainly include charred Angelica, parching Angelica with oil, parching Angelica with wine, and parching Angelica with soil, which have been widely used in TCM prescriptions. Polysaccharides are important chemical substances of AS. These compounds effectively treat liver diseases, shows hepatoprotectivity, and contributes directly to the therapeutic effect of AS. However, the precise molecular mechanism of the effects of the different AS products polysaccharide has not been comprehensively explored. The present investigation was designed to assess the effects and possible mechanisms of polysaccharide in the different AS products against carbon tetrachloride-induced liver injury.

MATERIALS AND METHODS

Liver injury was induced by intraperitoneal injection with Carbon tetrachloride (CCl4) in the mice. Gas chromatography-mass spectrometry (GC-MS) combined with pattern recognition approaches, namely, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were used to determine differentiating metabolites in plasma and liver tissue.

RESULTS

PCA and PLS-DA score plots of the liver injury group clustered separately from that of the control, while groups treated with polysaccharides from charred AS (ASTP), parching AS with soil (ASTUP), parching AS with wine (ASJP), parching AS with Sesame Oil (ASYP) clustered closely with the control. This result indicates that the metabolic profiles of the ASTP, ASTUP, ASJP, and ASYP groups are almost similar to those of the control. Potential metabolite biomarkers (six in the liver homogenates and seven in the plasma) were identified. These biomarkers include citric acid, succinic acid,glycine, palmitelaidic acid, arachidonic acid, fumaric acid, malic acid, valine, ananine, and hexadecanoic acid. Functional pathway analysis revealed that alterations in these metabolites are associated with lipid, amino acid, and energy metabolism. Notably, ASTP exhibited a potential pharmacological effect by regulating multiple perturbed pathways to the normal state.

CONCLUSION

It is likely that ASTP, ASTUP, ASJP, ASYP intervenes the metabolic process of liver injury mice by affecting the lipid and amino acid metabolism. Metabonomics is a robust and promising for the identification of biomarkers and elucidation of the mechanisms of a disease, thereby highlighting its importance in drug discovery.

摘要

民族药理学相关性

当归在中医药(TCM)中已有数千年的应用历史。当归的炮制产品主要包括炭制当归、油炙当归、酒炙当归和土炙当归,这些产品在 TCM 方剂中被广泛使用。多糖是当归的重要化学物质。这些化合物能有效治疗肝病,具有保肝作用,直接有助于当归的治疗效果。然而,不同当归制品多糖的确切分子机制尚未得到全面探索。本研究旨在评估不同当归制品多糖对四氯化碳诱导的肝损伤的作用及可能机制。

材料与方法

采用腹腔注射四氯化碳(CCl4)诱导小鼠肝损伤。采用气相色谱-质谱联用(GC-MS)结合模式识别方法,即主成分分析(PCA)和偏最小二乘判别分析(PLS-DA),确定血浆和肝组织中的差异代谢物。

结果

肝损伤组的 PCA 和 PLS-DA 得分图与对照组明显分开,而经炭制当归多糖(ASTP)、土炙当归多糖(ASTUP)、酒炙当归多糖(ASJP)和油炙当归多糖(ASYP)处理的组与对照组聚类紧密。这表明 ASTP、ASTUP、ASJP 和 ASYP 组的代谢谱几乎与对照组相似。鉴定出潜在的代谢物生物标志物(肝匀浆中有 6 种,血浆中有 7 种)。这些生物标志物包括柠檬酸、琥珀酸、甘氨酸、棕榈烯酸、花生四烯酸、富马酸、苹果酸、缬氨酸、丙氨酸和十六烷酸。功能途径分析表明,这些代谢物的变化与脂质、氨基酸和能量代谢有关。值得注意的是,ASTP 通过调节多个受干扰的途径使其恢复正常状态,表现出潜在的药理作用。

结论

ASTP、ASTUP、ASJP、ASYP 可能通过影响脂质和氨基酸代谢来干预肝损伤小鼠的代谢过程。代谢组学是一种强大而有前途的识别生物标志物和阐明疾病机制的方法,从而突出了其在药物发现中的重要性。

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