关键词: Achyranthes bidentata UHPLC–Q Exactive Orbitrap–HRMS chemical constituents prototype components and metabolites

Mesh : Animals Achyranthes / chemistry Chromatography, High Pressure Liquid / methods Rats Brain / metabolism Rats, Sprague-Dawley Male Mass Spectrometry / methods Drugs, Chinese Herbal / pharmacokinetics chemistry Infarction, Middle Cerebral Artery / metabolism blood Flavonoids / blood pharmacokinetics metabolism Alkaloids / blood pharmacokinetics chemistry metabolism

来  源:   DOI:10.3390/molecules29122840   PDF(Pubmed)

Abstract:
BACKGROUND: Achyranthes bidentata (AR) is a traditional Chinese herb used for the treatment of hypertension and cerebral ischemia, but its pharmacological effects are not known.
OBJECTIVE: We aimed to detect and accurately identify the components and metabolites of AR in the plasma and brain tissue of Sprague Dawley rats.
METHODS: We employed ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HR-MS) to detect AR components in the plasma and brain tissue of rats. The absorption and metabolites in the plasma and brain tissue of normal control rats and rats that underwent middle cerebral artery occlusion (MCAO) were characterized and compared.
RESULTS: A total of 281 compounds, including alkaloids, flavonoids, terpenoids, phenylpropanes, sugars and glycosides, steroids, triterpenes, amino acids, and peptides, was identified in samples of Achyranthes bidentata (TCM-AR). Four types of absorbable prototype components and 48 kinds of metabolites were identified in rats in the normal control plasma group which were given AR (AR plasma group), and five kinds of metabolites were identified in rats of the normal control brain tissue group which were given AR (AR brain group). Three absorbed prototype components and 13 metabolites were identified in the plasma of rats which underwent MCAO and were given AR (MCAO + AR plasma group). Six absorbed prototype components and two metabolites were identified in the brain tissue of rats who underwent MCAO and were administered AR (MCAO + AR brain group). These results showed that, after the oral administration of AR, the number of identified components in plasma was more than that in brain tissue. The number of prototype components in the AR plasma group was higher than that in the MCAO + AR plasma group, which may indicate that metabolite absorption in rats undergoing MCAO was worse. The number of prototype components in the MCAO + AR brain group was higher than that in the AR brain group, indicating that the blood-brain barrier was destroyed after MCAO, resulting in more compounds entering brain tissue.
CONCLUSIONS: UHPLC-HR-MS was used to rapidly analyze the components and metabolites of AR in the blood and brain of rats under normal and pathologic conditions, and to comprehensively characterize the components of TCM-AR. We also analyzed and compared the absorbable components and metabolites of normal rats under cerebral ischemia-reperfusion injury to explore the potential mechanism of action. This method could be applied to various Chinese herbs and disease models, which could promote TCM modernization.
摘要:
背景:牛膝(AR)是一种用于治疗高血压和脑缺血的传统中草药,但其药理作用尚不清楚。
目的:我们旨在检测并准确鉴定SpragueDawley大鼠血浆和脑组织中AR的成分和代谢产物。
方法:我们采用超高效液相色谱-高分辨率质谱(UHPLC-HR-MS)检测大鼠血浆和脑组织中的AR成分。对正常对照大鼠和大脑中动脉闭塞(MCAO)大鼠的血浆和脑组织中的吸收和代谢产物进行了表征和比较。
结果:共281种化合物,包括生物碱,黄酮类化合物,萜类化合物,苯基丙烷,糖和糖苷,类固醇,三萜,氨基酸,和肽,在牛膝(TCM-AR)样本中鉴定。在给予AR(AR血浆组)的正常对照血浆组大鼠中鉴定出4种可吸收原型成分和48种代谢产物,在给予AR(AR脑组)的正常对照脑组织组大鼠中鉴定出五种代谢产物。在接受MCAO并给予AR(MCAOAR血浆组)的大鼠血浆中鉴定出3种吸收的原型成分和13种代谢物。在接受MCAO并给予AR的大鼠的脑组织中鉴定出六种吸收的原型成分和两种代谢物(MCAO+AR脑组)。这些结果表明,口服AR后,血浆中确定的成分数量多于脑组织。AR等离子体组的原型组分数目高于MCAO+AR等离子体组,这可能表明接受MCAO的大鼠对代谢物的吸收较差。MCAO+AR脑组的原型组件数量高于AR脑组,表明MCAO后血脑屏障被破坏,导致更多的化合物进入脑组织。
结论:UHPLC-HR-MS可快速分析正常和病理条件下大鼠血液和脑中AR的成分和代谢产物。并全面表征TCM-AR的成分。我们还分析和比较了正常大鼠在脑缺血再灌注损伤下的可吸收成分和代谢产物,以探讨其潜在的作用机制。该方法可应用于各种中药和疾病模型,可以促进中医现代化。
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