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羟基红花黄色素A在正常及糖尿病心肌病小鼠中的药代动力学特征

Pharmacokinetic characteristics of hydroxysafflor yellow A in normal and diabetic cardiomyopathy mice.

作者信息

Yao Rui, Cao Yu, Jiang Ruibin, Zhang Xuan, Li Feng, Wang Siwang

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital, The Air Force Medical University, Xi'an, China.

Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, The Air Force Medical University, Xi'an, China.

出版信息

Biomed Chromatogr. 2021 Oct;35(10):e5173. doi: 10.1002/bmc.5173. Epub 2021 May 28.

Abstract

Hydroxysafflor yellow A (HSYA), a major active water-soluble component in Carthamus tinctorius L., is considered a potential antioxidant with protective effects against myocardial injury. However, its pharmacokinetic characteristics in normal and diabetic cardiomyopathy (DCM) mice remain unknown. This study was designed to investigate the differences in the pharmacokinetics of HSYA between normal and streptozotocin-induced DCM mice. HSYA in the mouse plasma was quantified using LC-MS/MS. Compared with the normal group, the DCM group showed a significantly higher area under the curve (AUC , AUC ) value and peak plasma concentration, suggesting a higher uptake of HSYA in the DCM mice, and a significantly lower plasma clearance and apparent volume of distribution, suggesting slower elimination of HSYA in the DCM mice. The levels of serum superoxide dismutase and glutathione peroxidase were significantly higher, and malondialdehyde content was significantly lower in DCM mice than in normal mice, indicating the antioxidative stress effect of HSYA. Furthermore, the correlation analysis revealed that the serum HSYA content in the DCM mice significantly positively correlated with antioxidant enzyme levels. These results showed that the pharmacokinetics of HSYA changed significantly in the DCM mice, and this may improve the antioxidative stress effect of the drug.

摘要

羟基红花黄色素A(HSYA)是红花中的一种主要活性水溶性成分,被认为是一种具有心肌损伤保护作用的潜在抗氧化剂。然而,其在正常小鼠和糖尿病性心肌病(DCM)小鼠中的药代动力学特征尚不清楚。本研究旨在探讨正常小鼠和链脲佐菌素诱导的DCM小鼠之间HSYA药代动力学的差异。采用液相色谱-串联质谱法(LC-MS/MS)对小鼠血浆中的HSYA进行定量分析。与正常组相比,DCM组的曲线下面积(AUC,AUC)值和血浆峰浓度显著更高,表明DCM小鼠对HSYA的摄取更高,而血浆清除率和表观分布容积显著更低,表明DCM小鼠中HSYA的消除更慢。DCM小鼠血清超氧化物歧化酶和谷胱甘肽过氧化物酶水平显著更高,丙二醛含量显著低于正常小鼠,表明HSYA具有抗氧化应激作用。此外,相关性分析显示,DCM小鼠血清HSYA含量与抗氧化酶水平显著正相关。这些结果表明,DCM小鼠中HSYA的药代动力学发生了显著变化,这可能会增强该药物的抗氧化应激作用。

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