Abstract
BackgroundPlantaginis 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.MethodsA 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).ResultsCompared 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.ConclusionsPlantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.
Highlights
Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear
Plantaginis semen decreased the level of serum uric acid (UA) in HUA rats After 28 days, rats fed potassium oxonate showed a significant change in the level of serum UA (Fig. 1a)
Relative intensities of 13 differential metabolites in serum samples of 6 groups are listed in Table 2, the specific p-values are provided in the supplementary material Table 8-Table 20. These findings suggested that the metabolic perturbations induced by HUA could be normalized by benzbromarone and Plantaginis Semen treatment
Summary
Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. The URAT1 and PI3K/Akt pathway are two important potential targets of Plantaginis Semen in the treatment of HUA. The PI3K/Akt pathway is able to trigger inflammatory and kidney injuries, impairing renal excretion of uric acid and HUA [18,19,20,21,22,23,24], the treatment of gouty nephropathy with Plantaginis Semen is mainly involved with the PI3K/ Akt signaling pathway [25]. There has been some research, it remains necessary to conduct in-depth studies on the pharmacological effects of Plantaginis Semen in treating HUA and its potential mechanism
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