School of pharmacy, Chongqing Medical University, Chongqing, 400016, PR China.
Chongqing Key Laboratory of Chinese Medicine New Drug Screening, Southwest University, Chongqing, 400715, PR China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):116814. doi: 10.1016/j.jep.2023.116814. Epub 2023 Aug 19.
In the Tibetan region of China, Thlaspi arvense L. is utilized for the prevention and treatment of hyperuricemia (HUA). Thlaspi arvense has been shown to lower uric acid levels in HUA rats in preliminary studies. However, the active components and mechanisms that account for its therapeutic effects remain elusive.
Network pharmacology, ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), mRNA-sequencing, and quantitative reverse transcription PCR (RT-PCR) were used to investigate the active ingredients of Thlaspi arvense against HUA in rats and elucidate the underlying mechanisms in this study.
A HUA rat model was established by a combination of intraperitoneal injection of potassium oxonate and intragastric administration of yeast extract. In the control and model groups, gastric gavage was performed to administer a normal saline solution, 4.5 mg kg benzbromarone in the positive drug group, and 3.5 g kgThlaspi arvense in the Thlaspi arvense group. After which network pharmacology and UPLC-Q-TOF-MS were employed to explore the active ingredients underlying the lowering of uric acid in Thlaspi arvense. In addition, mRNA-sequencing, network pharmacology and RT-PCR were applied to uncover Thlaspi arvense's mechanism of uric acid reduction.
The results showed that a two-week administration of the effective constituents of Thlaspi arvense led to a significant improvement in HUA rats, including lower serum levels of uric acid (UA), xanthine oxidase (XOD), creatinine (CREA), carbamide (UREA), aspartate aminotransferase (AST), alanine transaminase (ALT), and liver tissue activities of XOD, ADA, super (MDA). A network pharmacological analysis revealed 40 active compounds, including organic acids and flavonoids, that act on HUA therapeutic targets. These targets primarily focus on pathways related to uric acid metabolism modulation, such as XOD, SLC22A12, ABCG2, SLC22A8, and others, reducing HUA. The analysis of mRNA-sequencing as well as RT-PCR data from renal tissue demonstrated that the targets modulating uric acid metabolism were SLC22A8, SLC12A1, and SLC16A7.
In summary, organic acids and flavonoids may be the active components in Thlaspi arvense that alleviate HUA. The principal mechanisms are as follows: inhibition of XOD activity in the serum to reduce uric acid production, regulation of renal reabsorption and secretion of uric acid to increase uric acid excretion, and alleviation of oxidative stress reaction to decrease systemic damage and, eventually, treatment of HUA.
在中国西藏地区，菥蓂（Thlaspi arvense L.）被用于预防和治疗高尿酸血症（HUA）。初步研究表明，菥蓂可降低 HUA 大鼠的尿酸水平。然而，其治疗作用的活性成分和机制仍不清楚。
本研究采用网络药理学、超高效液相色谱-四极杆飞行时间串联质谱（UPLC-Q-TOF-MS）、mRNA 测序和实时定量逆转录 PCR（RT-PCR）技术，研究菥蓂治疗大鼠 HUA 的活性成分，并探讨其作用机制。
采用氧嗪酸钾腹腔注射联合酵母提取物灌胃的方法建立 HUA 大鼠模型。在对照组和模型组中，分别给予生理盐水灌胃、阳性药物苯溴马隆 4.5mg·kg-1 灌胃和菥蓂 3.5g·kg-1 灌胃。采用网络药理学和 UPLC-Q-TOF-MS 技术探索菥蓂降低尿酸的活性成分。此外，采用 mRNA 测序、网络药理学和 RT-PCR 技术揭示菥蓂降低尿酸的作用机制。
研究结果表明，连续两周给予菥蓂有效成分可显著改善 HUA 大鼠的病情，包括降低血清尿酸（UA）、黄嘌呤氧化酶（XOD）、肌酐（CREA）、尿素（UREA）、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和肝组织 XOD、ADA、超氧化物歧化酶（MDA）的活性。网络药理学分析显示，有 40 种活性化合物，包括有机酸和黄酮类化合物，作用于 HUA 治疗靶点。这些靶点主要集中在尿酸代谢调节相关的途径上，如 XOD、SLC22A12、ABCG2、SLC22A8 等，从而降低 HUA。肾组织 mRNA 测序和 RT-PCR 数据分析表明，调节尿酸代谢的靶点为 SLC22A8、SLC12A1 和 SLC16A7。
综上所述，有机酸和黄酮类化合物可能是菥蓂缓解 HUA 的活性成分。其主要作用机制为：抑制血清中 XOD 的活性，减少尿酸的生成；调节肾脏对尿酸的重吸收和分泌，增加尿酸的排泄；减轻氧化应激反应，减少全身损伤，最终治疗 HUA。
