First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 300193, Tianjin, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
J Ethnopharmacol. 2023 Sep 15;313:116589. doi: 10.1016/j.jep.2023.116589. Epub 2023 May 2.
Perilla Folium (PF), is a traditional medicinal material with the homology of medicine and food in China and has been widely used due to its rich nutritional content and medicinal value. The hepatoprotective effects of PF extract include their protection against acute hepatic injury, tert-butylhydroperoxide (t-BHP) induced oxidative damage, and Lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced hepatic injury have been well studied. However, there are few reports on the pharmacokinetics studies of PF extract in acute hepatic injury model rats, and the anti-hepatic injury activity of PF is still unclear.
The differences in the plasma pharmacokinetic of 21 active compounds between the normal and model groups were compared， and established pharmacokinetics/pharmacodynamics (PK/PD) modeling was to analyze the hepatoprotective effects of PF.
The acute hepatic injury model was induced with an intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-GalN), and the plasma pharmacokinetics of 21 active compounds of PF were analyzed in the normal and model groups using ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The correlation between plasma components and hepatoprotective effects indicators (the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH)) in the model group was also investigated and established a Pharmacokinetic/pharmacodynamic (PK/PD) correlation analysis of the hepatoprotective effects of PF.
The results revealed that organic acid compounds possessed the characteristics of faster absorption, shorter peak time and slower metabolism, while the flavonoid compounds had slower absorption and longer peak time, and the pharmacokinetics of various components were significantly affected after modeling. The results of PK/PD modeling analysis demonstrated that the plasma drug concentration of each component existed a good correlation with the three AST, ALT, and LDH, and the lag time of the efficacy of each component is relatively long.
The plasma drug concentration of each component existed a good correlation with the three AST, ALT, and LDH, and the lag time of the efficacy of each component is relatively long in vivo.
紫苏（PF）是一种药食同源的传统药材，由于其丰富的营养成分和药用价值而被广泛应用。PF 提取物的保肝作用包括对急性肝损伤、叔丁基过氧化物（t-BHP）诱导的氧化损伤、脂多糖（LPS）和 D-半乳糖胺（D-GalN）诱导的肝损伤的保护作用已有很好的研究。然而，关于 PF 提取物在急性肝损伤模型大鼠中的药代动力学研究报道较少，PF 的抗肝损伤活性仍不清楚。
比较正常组和模型组之间 21 种活性化合物的血浆药代动力学差异，并建立药代动力学/药效学（PK/PD）模型分析 PF 的保肝作用。
采用腹腔注射脂多糖（LPS）和 D-半乳糖胺（D-GalN）诱导急性肝损伤模型，采用超高效液相色谱/串联质谱（UPLC-MS/MS）法分析正常组和模型组 PF 中 21 种活性化合物的血浆药代动力学。还考察了模型组中血浆成分与保肝作用指标（丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和乳酸脱氢酶（LDH））的相关性，并建立了 PF 保肝作用的 PK/PD 相关性分析。
结果表明，有机酸类化合物具有吸收快、达峰时间短、代谢快的特点，而黄酮类化合物吸收慢、达峰时间长，各成分的药代动力学在建模后均受到显著影响。PK/PD 模型分析结果表明，各成分的血浆药物浓度与三个 AST、ALT 和 LDH 均存在良好的相关性，各成分的疗效滞后时间较长。
各成分的血浆药物浓度与三个 AST、ALT 和 LDH 均存在良好的相关性，各成分的疗效滞后时间较长。
