摘要
民族药理学意义：Siraitia grosvenorii（S. grosvenorii）是一种用于预防肺部疾病的传统草药。据推测，其主要活性成分是皂苷和类黄酮。然而，其活性成分在体内的动态分布以及在肺靶组织中的蓄积量仍不明确：研究目的：本研究调查了大鼠血液、心脏、肝脏、脾脏、肺脏和肾脏中罗汉果提取物中 9 种生物活性成分的动态分布模式及其肺靶向性：采用UPLC-MS/MS法测定大鼠血液、心脏、肝脏、脾脏、肺脏和肾脏中9种生物活性成分（茜草皂甙I、茜草宁、11-O-茜草皂甙V、茜草皂甙II-E、茜草皂甙III-E、茜草皂甙IV-A、茜草皂甙V、茜草皂甙VI和山奈苷）的含量。绘制了每个样品中各成分的浓度-时间曲线，并计算了药代动力学参数：结果：9种生物活性成分在肺组织中的AUC0→∞和Cmax明显高于心、肝、脾和肾组织。例如，莫高苷 V 在肺组织中的 AUC0→∞ 是血液和其他组织的 7.20 至 55.54 倍，Cmax 是血液和其他组织的 3.315 至 96.70 倍。9 种生物活性成分的肺靶效率在 1.885 至 15.80 之间，表明具有药理作用的蛇床子活性成分高度集中在肺靶组织中。9 种生物活性成分在血液中的最大作用时间为 10.20 至 100.2 分钟，而在心脏和肝脏中的最大作用时间为 20 分钟。所有成分在肺中的 Tmax 为 50 分钟，而在脾脏和肾脏中的 Tmax 为 80 至 100 分钟，这表明 9 种生物活性成分迅速进入血液，然后大量分布到心脏和肝脏，再大量进入肺组织，最终分布到脾脏和肾脏。9种生物活性成分的消除半衰期（T1/2）大多小于1小时，其中大多数成分的最大消除半衰期（MRT）小于3小时：结论：罗汉果是一种天然的肺靶向中药，临床用药应根据其在肺组织中的Tmax、Cmax、AUC0→∞、T1/2和MET0→∞等药动学参数设计精确、严谨、合理的用药方案。Ethnopharmacological relevance: Siraitia grosvenorii (S. grosvenorii) is a traditional herbal medicine employed for the prevention of lung diseases. Mogrosides and flavonoids are postulated to be the principal active components. Nevertheless, the dynamic distribution of its active components in vivo and the amount of accumulation in the lung target tissue remain indistinct.
Aim of the study: This study investigates the dynamic distribution patterns of 9 bioactive components within the extract of S. grosvenorii in rat blood, heart, liver, spleen, lung, and kidney, along with its pulmonary targeting.
Materials and methods: The blood, heart, liver, spleen, lung, and kidney samples of rats were obtained at diverse time points after oral administration of S. grosvenorii decotion, and a UPLC-MS/MS method was developed to determine the contents of 9 bioactive components (Siamenoside I, Grosvenorine, 11-O-Mogroside V, Mogroside II-E, Mogroside III-E, Mogroside IV-A, Mogroside V, Mogroside VI and Kaempferitrin) within the samples. The concentration-time curves of each component in each sample were plotted and the pharmacokinetic parameters were computed.
Results: The AUC0→∞ and Cmax of 9 bioactive components in lung tissue were conspicuously higher than those in heart, liver, spleen, and kidney. For instance, the AUC0→∞ of Mogroside V in lung tissue was 7.20 to 55.54 times higher than that in blood and other tissues, and the Cmax in lung tissue was 3.315 to 96.70 times higher than that in blood and other tissues. The lung target efficiency of 9 bioactive components ranged from 1.885 to 15.80, indicating that the active components of S. grosvenorii exerting pharmacological effects are highly concentrated in the lung target tissue. The Tmax of 9 bioactive components in blood was within the range of 10.20 to 100.2 min, while the Tmax of the heart and liver was 20 min. The Tmax of all the components in the lung was 50 min, while the Tmax of the spleen and kidney was from 80 to 100 min, suggesting that 9 bioactive components entered the blood rapidly and then distributed to the heart and liver in large quantities, before entering the lung tissue in large quantities and eventually distributing to the spleen and kidney. The elimination half-life (T1/2) of the majority of 9 bioactive components was less than 1 hour, and the MRT of most of them was less than 3 hours.
Conclusions: S. grosvenorii is a naturally lung-targeted herbal medicine, and the clinical administration ought to be based on pharmacokinetic parameters such as Tmax, Cmax, AUC0→∞, T1/2, and MET0→∞ in lung tissue for designing a precise, rigorous, and rational administration plan.
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