{"title":"大鼠多次服用菟丝子精盐溶液治疗复发性自然流产的药代动力学和金丝桃素、黄芪苷、山柰酚-3-O-β-D-葡萄糖醛酸的组织分布研究","authors":"Zhitong Yang, Kaiwen Chen, Yuting Zhang, Baiyang Xu, Yu Huang, Xue Zhang, Zilu Liu, Tongsheng Wang, Deling Wu, Tangyi Peng, Tulin Lu, Hao Cai, Xiaoli Wang","doi":"10.3389/fphar.2024.1440810","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong><i>Semen Cuscutae</i> is a traditional Chinese medicine (TCM) that tonifies the kidneys and prevents miscarriage. According to Chinese medicine theory, kidney deficiency is one of the main causes of recurrent spontaneous abortion (RSA). The previous studies showed that raw product of <i>Semen Cuscutae</i> (SP) and <i>Semen Cuscutae</i> processed with salt solution (YP) have ameliorative effects on RSA, and that YP is superior to SP. However, the active components of YP to ameliorate RSA remain unclear and require further studies. The objective of this study is to investigate the active components of YP in ameliorating RSA.</p><p><strong>Methods: </strong>First, a rat model of RSA was established using hydroxyurea in combination with mifepristone. Aqueous decoction of YP was given by gavage to rats. Second, pregnant rats were sampled on days 5, 7, 9, 10 and 12 during the modelling period. The content of Hyperin (HY), astragalin (AS) and kaempferol-3-O-β-D-glucuronide (KA) in blood and liver, heart, spleen, lung and kidney tissues were detected by liquid chromatography-mass spectrometry (LC-MS). The pharmacodynamic indicators including progesterone (P), chorionic gonadotropin β (β-HCG), estradiol (E2), tumor necrosis factor-α (TFN-α), interleukin 4 (IL-4), and tryptophan (TRP) were measured by enzyme-linked immunosorbent assay (ELISA) Pearson's correlation analysis and grey relational analysis were used to establish the relationship between the pharmacodynamic indexes and chemical constituents.</p><p><strong>Results: </strong>The pharmacokinetic results showed that the area under curve (AUC) value of KA was the largest. The tissue distribution results showed that astragalin was widely distributed in liver, heart, spleen, lung and kidney in the RSA model rats, while HY was detected only in the uterus, and KA was detected only in the kidney. The pearson correlationl analysis showed that KA was significantly and positively correlated with the contents of E2, P, β-HCG and TRP. Both AS and HY were significantly negatively correlated with the content of TNF-α, respectively.</p><p><strong>Discussion: </strong>This study reveals the pharmacokinetics and tissue distribution of KA, AS and HY in rats with RSA. It was elucidated that all three were involved in the regulation of progesterone levels and immune function. It initially revealed the mechanism of action of YP in enhancing the improvement of RSA, and it provided a theoretical basis for the quality assessment of YP.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439818/pdf/","citationCount":"0","resultStr":"{\"title\":\"Study on pharmacokinetic and tissue distribution of hyperin, astragalin, kaempferol-3-O-β-D-glucuronide from rats with multiple administrations of Semen Cuscutae processed with salt solution with effect of treating recurrent spontaneous abortion.\",\"authors\":\"Zhitong Yang, Kaiwen Chen, Yuting Zhang, Baiyang Xu, Yu Huang, Xue Zhang, Zilu Liu, Tongsheng Wang, Deling Wu, Tangyi Peng, Tulin Lu, Hao Cai, Xiaoli Wang\",\"doi\":\"10.3389/fphar.2024.1440810\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong><i>Semen Cuscutae</i> is a traditional Chinese medicine (TCM) that tonifies the kidneys and prevents miscarriage. According to Chinese medicine theory, kidney deficiency is one of the main causes of recurrent spontaneous abortion (RSA). The previous studies showed that raw product of <i>Semen Cuscutae</i> (SP) and <i>Semen Cuscutae</i> processed with salt solution (YP) have ameliorative effects on RSA, and that YP is superior to SP. However, the active components of YP to ameliorate RSA remain unclear and require further studies. The objective of this study is to investigate the active components of YP in ameliorating RSA.</p><p><strong>Methods: </strong>First, a rat model of RSA was established using hydroxyurea in combination with mifepristone. Aqueous decoction of YP was given by gavage to rats. Second, pregnant rats were sampled on days 5, 7, 9, 10 and 12 during the modelling period. The content of Hyperin (HY), astragalin (AS) and kaempferol-3-O-β-D-glucuronide (KA) in blood and liver, heart, spleen, lung and kidney tissues were detected by liquid chromatography-mass spectrometry (LC-MS). The pharmacodynamic indicators including progesterone (P), chorionic gonadotropin β (β-HCG), estradiol (E2), tumor necrosis factor-α (TFN-α), interleukin 4 (IL-4), and tryptophan (TRP) were measured by enzyme-linked immunosorbent assay (ELISA) Pearson's correlation analysis and grey relational analysis were used to establish the relationship between the pharmacodynamic indexes and chemical constituents.</p><p><strong>Results: </strong>The pharmacokinetic results showed that the area under curve (AUC) value of KA was the largest. The tissue distribution results showed that astragalin was widely distributed in liver, heart, spleen, lung and kidney in the RSA model rats, while HY was detected only in the uterus, and KA was detected only in the kidney. The pearson correlationl analysis showed that KA was significantly and positively correlated with the contents of E2, P, β-HCG and TRP. Both AS and HY were significantly negatively correlated with the content of TNF-α, respectively.</p><p><strong>Discussion: </strong>This study reveals the pharmacokinetics and tissue distribution of KA, AS and HY in rats with RSA. It was elucidated that all three were involved in the regulation of progesterone levels and immune function. 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引用次数: 0
摘要
简介菟丝子是一种传统中药,具有补肾和预防流产的作用。中医理论认为,肾虚是导致反复自然流产(RSA)的主要原因之一。以往的研究表明,菟丝子原液(SP)和菟丝子盐溶液(YP)对复发性自然流产(RSA)有改善作用,且 YP 优于 SP。然而,YP中改善RSA的活性成分仍不清楚,需要进一步研究。本研究的目的是探究 YP 在改善 RSA 方面的活性成分:方法:首先,使用羟基脲联合米非司酮建立大鼠 RSA 模型。方法:首先,使用羟基脲联合米非司酮建立 RSA 大鼠模型,并通过灌胃给大鼠服用叶酸水煎剂。其次,在建模期间的第 5、7、9、10 和 12 天对怀孕大鼠进行采样。采用液相色谱-质谱法(LC-MS)检测大鼠血液和肝、心、脾、肺、肾组织中金丝桃素(HY)、黄芪甲素(AS)和山柰酚-3-O-β-D-葡萄糖醛酸苷(KA)的含量。药效学指标包括孕酮(P)、绒毛膜促性腺激素 β(β-HCG)、雌二醇(E2)、肿瘤坏死因子-α(TFN-α)、白细胞介素 4(IL-4)、采用皮尔逊相关分析和灰色关系分析确定药效学指标与化学成分之间的关系。结果药代动力学结果表明,KA的曲线下面积(AUC)值最大。组织分布结果表明,黄芪甲素广泛分布于 RSA 模型大鼠的肝、心、脾、肺和肾中,而 HY 仅在子宫中检出,KA 仅在肾中检出。皮尔逊相关分析表明,KA与E2、P、β-HCG和TRP的含量呈显著正相关。AS 和 HY 分别与 TNF-α 的含量呈显著负相关:本研究揭示了 KA、AS 和 HY 在 RSA 大鼠体内的药代动力学和组织分布。讨论:本研究揭示了 KA、AS 和 HY 在 RSA 大鼠体内的药代动力学和组织分布,阐明了三者均参与孕酮水平和免疫功能的调节。初步揭示了YP促进改善RSA的作用机制,为YP的质量评价提供了理论依据。
Study on pharmacokinetic and tissue distribution of hyperin, astragalin, kaempferol-3-O-β-D-glucuronide from rats with multiple administrations of Semen Cuscutae processed with salt solution with effect of treating recurrent spontaneous abortion.
Introduction: Semen Cuscutae is a traditional Chinese medicine (TCM) that tonifies the kidneys and prevents miscarriage. According to Chinese medicine theory, kidney deficiency is one of the main causes of recurrent spontaneous abortion (RSA). The previous studies showed that raw product of Semen Cuscutae (SP) and Semen Cuscutae processed with salt solution (YP) have ameliorative effects on RSA, and that YP is superior to SP. However, the active components of YP to ameliorate RSA remain unclear and require further studies. The objective of this study is to investigate the active components of YP in ameliorating RSA.
Methods: First, a rat model of RSA was established using hydroxyurea in combination with mifepristone. Aqueous decoction of YP was given by gavage to rats. Second, pregnant rats were sampled on days 5, 7, 9, 10 and 12 during the modelling period. The content of Hyperin (HY), astragalin (AS) and kaempferol-3-O-β-D-glucuronide (KA) in blood and liver, heart, spleen, lung and kidney tissues were detected by liquid chromatography-mass spectrometry (LC-MS). The pharmacodynamic indicators including progesterone (P), chorionic gonadotropin β (β-HCG), estradiol (E2), tumor necrosis factor-α (TFN-α), interleukin 4 (IL-4), and tryptophan (TRP) were measured by enzyme-linked immunosorbent assay (ELISA) Pearson's correlation analysis and grey relational analysis were used to establish the relationship between the pharmacodynamic indexes and chemical constituents.
Results: The pharmacokinetic results showed that the area under curve (AUC) value of KA was the largest. The tissue distribution results showed that astragalin was widely distributed in liver, heart, spleen, lung and kidney in the RSA model rats, while HY was detected only in the uterus, and KA was detected only in the kidney. The pearson correlationl analysis showed that KA was significantly and positively correlated with the contents of E2, P, β-HCG and TRP. Both AS and HY were significantly negatively correlated with the content of TNF-α, respectively.
Discussion: This study reveals the pharmacokinetics and tissue distribution of KA, AS and HY in rats with RSA. It was elucidated that all three were involved in the regulation of progesterone levels and immune function. It initially revealed the mechanism of action of YP in enhancing the improvement of RSA, and it provided a theoretical basis for the quality assessment of YP.
期刊介绍:
Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.