Ganoderma lucidum polysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters
Ganoderma lucidum polysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters
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灵芝多糖肽通过调节腺苷脱氨酶和尿酸转运蛋白缓解高尿酸血症
DOI：
10.1039/d2fo02431d
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发表时间：
2022-11-17
期刊：
影响因子：
6.1
通讯作者：
Yang，Baoxue
中科院分区：
文献类型：
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作者：
Lin，Simei;Meng，Jia;Yang，Baoxue
高尿酸血症(HUA)影响人类健康，参与常见慢性病的发病机制。以往的研究表明，灵芝提取物能降低动物体内的HUA。然而，灵芝提取物改善HUA的有效成分和药理机制尚不清楚。本研究采用氧酸钾(PO)诱导的小鼠模型和腺苷诱导的细胞模型，研究灵芝多糖肽(GLPP)的抗华作用及其相关机制。实验结果表明，GLPP能剂量依赖性地降低HUA小鼠的血尿酸(UA)，降幅达40.6%。此外，GLPP通过抑制肝脏和血液中腺苷脱氨酶(ADA)的活性，显著减少尿酸的产生，并通过降低葡萄糖转运体9(GLUT9)的表达和增加肾脏有机阴离子转运体1(OAT1)的表达而增加尿酸的排泄。腺苷诱导的细胞模型显示，GLPP对ADA活性的抑制作用可能是GLPP减轻HUA的主要原因。此外，GLPP还能剂量依赖性地减轻PO所致的肾组织病理损伤。实验结果表明，GLPP通过调节尿酸的产生和排泄而发挥抗HUA的作用，提示GLPP有可能发展成为治疗HUA的药物。
Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.