背景:近年来,除了高血压,高血糖症,和高脂血症,高尿酸血症(HUA)的患病率已大大增加。作为第四大健康风险因素,HUA可影响肾脏和心血管系统。菊花是一种含有黄酮类化合物的传统中成药,具有降低尿酸(UA)的作用。然而,富含菊花的黄酮部分(CYM。E)介导的HUA缓解仍未阐明。
目的:本研究旨在阐明CYM的疗效。E在预防和治疗HUA及其对UA相关转运蛋白的特异性影响,探索可能的机制。
方法:CYM中buddleoside的含量。E通过高效液相色谱法测定。在小鼠模型中使用腺嘌呤和草酸钾诱导HUA。随后,小鼠服用10mg/kg别嘌醇,和30、60和90mg/kgCYM。E评价CYM的作用。E对HUA小鼠模子。在这里,血浆尿酸(UA),肌酐(CR),血尿素氮(BUN),总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-c),低密度脂蛋白胆固醇(LDL-c)含量,随着血清谷丙转氨酶(ALT),并测定天冬氨酸转氨酶(AST)活性。此外,测定肝脏中的黄嘌呤氧化酶(XOD)和腺苷脱氨酶(ADA)活性。通过苏木精和伊红染色检查肝脏和肾脏组织的组织形态。促进葡萄糖转运蛋白9(GLUT9)的信使RNA(mRNA)表达,通过实时定量聚合酶链反应评估肾脏中的有机阴离子转运体(OAT)1,OAT3和三磷酸腺苷结合盒亚家族G2(ABCG2).此外,尿酸转运蛋白1(URAT1)的表达,肾脏中的GLUT9、OAT1和OAT3,通过免疫组织化学和蛋白质印迹测定OAT4和ABCG2蛋白。
结果:CYM中buddleoside的含量。E约为32.77%。CYM.E改善HUA小鼠的体重和自主活动。此外,它降低了血浆UA,BUN,和CR水平和血清ALT和AST活性,从而改善肝肾功能,这进一步降低了血浆UA含量。CYM.E减少对肾脏的组织病理学损害。此外,它降低了血浆TC,TG,和LDL-c水平,从而改善脂质代谢紊乱。CYM.E给药抑制肝脏XOD和ADA活性,并降低肾脏GLUT9的mRNA表达。CYM.E抑制肾脏URAT1、GLUT9和OAT4的蛋白表达,增加肾脏OAT1、OAT3和ABCG2的mRNA和蛋白表达。总之,这些结果表明CYM。E可抑制UA的产生,促进UA的重吸收及其排泄。
BACKGROUND: In recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated.
OBJECTIVE: This study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism.
METHODS: The buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting.
RESULTS: The buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.