Preliminary study on the material basis and mechanism underlying uric acid reduction by Thlaspi arvense L.

Abstract

Ethnopharmacological relevanceIn 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. Aim of studyNetwork 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. Materials and methodsA 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−1 benzbromarone in the positive drug group, and 3.5 g kg−1Thlaspi 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. ResultsThe 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. ConclusionIn 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.