Plantaginis Semen Ameliorates Hyperuricemia Induced by Potassium Oxonate

Plantaginis semen is the dried ripe seed of <i>Plantago asiatica</i> L. or <i>Plantago depressa</i> Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (<i>Urat1</i>) and glucose transporter 9 (<i>Glut9</i>) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of <i>Slc7a8</i>, <i>Pck1</i>, <i>Mgll</i>, and <i>Bhmt</i> were significantly elevated, and <i>Fkbp5</i> was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved <i>Pparα</i>, <i>Pparγ</i>, <i>Lpl</i>, <i>Plin5</i>, <i>Atgl</i>, and <i>Hsl</i> were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.