基于化学成分和代谢组学分析的传统去皮净制对何首乌肝毒性影响探讨

Translated title of the contribution: Effect of traditional peeling on the hepatotoxicity of Polygonum multiflorum Thunb. based on chemical composition analysis and metabolomics

陈潘, 罗寒燕, 张伟豪, 李新星, 陈锦津, 朱利霞, 许军*, 赵中振*, 魏胜利*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

目的:比较去皮对何首乌水提物化学成分及潜在肝毒性的影响。方法:用UPLC-Q-TOFMS技术分析去皮何首乌水提物、粗皮水提物的化学成分并鉴定,结合多元统计分析对比何首乌不同组织部位水提物肝毒性成分含量差异。选取雄性SD大鼠40只,随机分为正常组,未去皮何首乌水提物给药组,去皮何首乌水提物给药组,粗皮水提物给药组,各给药组大鼠灌胃剂量20g·kg-1(按照未去皮何首乌药材量计算),正常组灌胃等体积去离子水,每日一次,连续灌胃35d,搜集血清、肝脏。通过血清生化指标分析、肝病理学观察比较各组肝损伤情况。通过代谢组学分析,比较各给药组大鼠肝损伤生物标志物水平的变化。结果:共鉴定出何首乌中190种化学成分,去皮显著减少何首乌水提物中肝毒性成分2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(THSG)和潜在肝毒性成分THSG二聚体(Di-THSG)及蒽醌类成分,并明显减轻何首乌对大鼠的肝脏病理损伤。代谢组学分析结果提示,相对不去皮给药,去皮给药显著回调大鼠体内内源性肝损伤生物标志物二十二碳六烯酸、哌啶酸、甘羟胆酸、酪氨酸和还原型谷胱甘肽水平,与正常组差异无统计学意义。结论:本研究明确了去皮可减少何首乌水提物中二苯乙烯苷类和蒽醌类肝毒性成分,其可能通过减弱何首乌对内源性肝损伤生物标志物的扰动降低药物的肝病理损伤作用,为何首乌的加工方法标准化提供了科学依据。

Objective: To compare the effect of peeling on the chemical compositions and potential hepatotoxicity of the water extract of Polygonum multiflorum Thunb. (Heshouwu). Methods: The chemical constituents of water extract of peeled Heshouwu, and water extract of peels were analyzed by UPLC-Q-TOF-MS, before the identification. Multivariate statistical analysis was used to compare the levels of hepatotoxic constituents in different parts of Heshouwu. Totally 40 male SD rats were selected and randomly divided into a normal group, a water extract of unpeeled Heshouwu group and a water extract of peeled Heshouwu group. The rats in each treatment group were orally given a dose of 20 g·kg-1 (calculated according to the amount of unpeeled Heshouwu materials), while the rats in the normal group were orally given an equivalent volume of deionized water once daily for 35 consecutive days, before the serum and liver samples were collected. Serum biochemical analysis and liver pathology were used to compare the liver injury in each group, while metabolomics was used to compare the level of liver injury biomarkers of rats in each administration group. Results: Totally 190 chemical constituents were identified in Heshouwu . Peeling significantly reduced the levels of hepatotoxic constituent 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside and potentially hepatotoxic constituent dimer of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside,as well as anthraquinones in the water extract of Heshouwu. Peeling also obviously alleviated the liver pathological damage of Heshouwu to rats. Metabolomic analysis showed that peeled Heshouwu greatly reversed the levels of endogenous liver injury biomarkers such as docosahexanoic acid, pipecolinic acid, glycohyocholic acid, tyrosine and reduced glutathione in rats compared with unpeeled Heshouwu. Conclusion: Peeling can reduce the hepatotoxic constituents of stilbene glycosides and anthraquinones in the water extract of Heshouwu and may reduce the hepatic pathological damage effect of Heshouwu by attenuating the perturbation of endogenous liver injury biomarkers. This study provides a scientific basis for the standardisation Heshouwu processing.
Translated title of the contributionEffect of traditional peeling on the hepatotoxicity of Polygonum multiflorum Thunb. based on chemical composition analysis and metabolomics
Original languageChinese (Simplified)
Pages (from-to)3169-3180
Number of pages12
Journal中南药学
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2024

User-Defined Keywords

  • 代谢组学
  • 肝毒性
  • 何首乌
  • 加工
  • 去皮
  • metabolomics
  • hepatotoxicity
  • Polygonum multiflorum Thunb.
  • processing
  • peeling

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