Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

Abstract

Background Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. Methods A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875 or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Results Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was most affected. These perturbations were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. Conclusions Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.

Tongbixiao Pills Improve Gout by Reducing Uric Acid Levels and Inhibiting Inflammation

“…10 Uric acid-lowering treatment is beneficial for the dissolution of sodium urate crystals, thereby preventing gout attacks. 11 In the clinic, the current drugs for treating hyperuricemia mainly include uric acid excretion agents and xanthine oxidase (XOD) inhibitors; 12 however, challenges such as side effects and easy recurrence after drug withdrawal exist. 13 For example, although febuxostat and allopurinol drugs can reduce uric acid levels, they increase the risk of cardiovascular disease.…”

Investigation of pathogenesis of hyperuricemia based on untargeted and targeted metabolomics

“…The screening of candidate biomarkers should meet the following three conditions: AUC greater than 0.9 (high accuracy); It has high participation in the metabolic pathway. We refer to the frequency mentioned in previous studies 35 – 38 . …”

Beneficial effects of psyllium on the prevention and treatment of cardiometabolic diseases

“…In the potassium oxonate-induced hyperuricemia rat, psyllium treatment may achieve the effect of treating hyperuricemia by downregulating the mRNA expression of URAT1. 123 Additionally, a high dose of psyllium possesses inhibitory activity over the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, which plays a role in anti-inflammatory and renal protection, and ultimately indirectly improves hyperuricemia.…”

“…These studies demonstrated that psyllium is a potential therapeutic agent for the treatment of hyperuricemia via inhibiting XOD activities and URAT1 expression. 123…”