Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create s...Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create safer and more potent therapeutic medications since the current clinical treatment for HUA has a number of negative effects.Objective:To explore the antihyperuricemic benefits of the total flavonoids from Carya cathayensis leaves(CCTF)in HUA model mice and to elucidate the underlying mechanisms.Methods:The mouse HUA model was induced with potassium oxonate and hypoxanthine and then the mice were given normal saline,allopurinol,or various dosages of CCTF for one week.The weight of the mice was recorded,followed by measurements of their blood uric acid(UA),creatinine(Cr),urea nitrogen(BUN),aspar-tate aminotransferase(AST),alanine aminotransferase(ALT),and xanthine oxidase(XOD)activity.Hematoxylin and eosin(H&E)staining and Manson staining were used to simultaneously detect pathological abnormalities in the liver and kidney tissues.Afterward,the mRNA expression of urate transporters in kidney was determined by qRT‒PCR experiments,including ATP-binding cassette transporter subfamily G member 2(Abcg2),urate trans-porter 1(Urat1),and glucose transporter 9(Glut9).Finally,immunohistochemistry(IHC)staining was performed to confirm ABCG2 protein expression in the kidney.Results:In contrast to the model group,the CCTF group lowered blood levels of UA,Cr,BUN,ALT,and AST in serum,downregulated XOD levels in serum and liver,and significantly improved liver and renal damage,exhibiting outstanding antihyperuricemic effects.The levels of Urat1 and Glut9 were further shown to be much lower in the kidney,whereas both Abcg2 expression and ABCG2 level were increased,according to the findings.Conclusion:CCTF ameliorated hyperuricemia-related kidney damage and had antihyperuricemic effects,suggest-ing that CCTF might have the potential to protect against HUA by regulating the expression of relative urate transporters and XOD.展开更多
基金The Zhejiang Traditional Chinese Medicine Administration(CN)(Project No.2023ZF012).
文摘Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create safer and more potent therapeutic medications since the current clinical treatment for HUA has a number of negative effects.Objective:To explore the antihyperuricemic benefits of the total flavonoids from Carya cathayensis leaves(CCTF)in HUA model mice and to elucidate the underlying mechanisms.Methods:The mouse HUA model was induced with potassium oxonate and hypoxanthine and then the mice were given normal saline,allopurinol,or various dosages of CCTF for one week.The weight of the mice was recorded,followed by measurements of their blood uric acid(UA),creatinine(Cr),urea nitrogen(BUN),aspar-tate aminotransferase(AST),alanine aminotransferase(ALT),and xanthine oxidase(XOD)activity.Hematoxylin and eosin(H&E)staining and Manson staining were used to simultaneously detect pathological abnormalities in the liver and kidney tissues.Afterward,the mRNA expression of urate transporters in kidney was determined by qRT‒PCR experiments,including ATP-binding cassette transporter subfamily G member 2(Abcg2),urate trans-porter 1(Urat1),and glucose transporter 9(Glut9).Finally,immunohistochemistry(IHC)staining was performed to confirm ABCG2 protein expression in the kidney.Results:In contrast to the model group,the CCTF group lowered blood levels of UA,Cr,BUN,ALT,and AST in serum,downregulated XOD levels in serum and liver,and significantly improved liver and renal damage,exhibiting outstanding antihyperuricemic effects.The levels of Urat1 and Glut9 were further shown to be much lower in the kidney,whereas both Abcg2 expression and ABCG2 level were increased,according to the findings.Conclusion:CCTF ameliorated hyperuricemia-related kidney damage and had antihyperuricemic effects,suggest-ing that CCTF might have the potential to protect against HUA by regulating the expression of relative urate transporters and XOD.
文摘目的：研究山核桃叶总黄酮及其4种单体化合物球松素查尔酮、松属素、白杨素、汉黄芩素对血管紧张素Ⅱ（angiotensin Ⅱ，AngⅡ）诱导的血管平滑肌细胞（vascular smooth muscle cells，VSMC）增殖和迁移的作用。方法：组织贴块法培养大鼠胸主动脉VSMC。调细胞密度2．0×10^4／mL，血清饥饿处理后用100nmol·L^-1 Ang Ⅱ诱导增殖12h。调细胞密度6．0×10^4／mL，用100nmol·L^-1 Ang Ⅱ诱导迁移12h。均给予12．5～62．5mg·L～总黄酮，10～50mg·L^-1球松素查尔酮、松属素、白杨素、汉黄芩素作用12h。用细胞计数法检测VSMC增殖，伤口愈合实验检测VSMC迁移。结果：12．5mg·L～总黄酮可剂量依赖性地显著抑制AngII诱导的VSMC增殖，50mg·L。球松素查尔酮、白杨素和汉黄芩素对AngⅡ诱导的VSMC增殖有微弱抑制。12．5mg·L^-1总黄酮，10mg·L^-1球松素查尔酮、松属素、白杨素、汉黄芩素均能剂量依赖性地显著抑制AngⅡ诱导的VSMC迁移。其中总黄酮、白杨素、汉黄芩素的效果优于松属素和球松素查尔酮。结论：山核桃叶总黄酮能有效抑制AngII诱导的VSMC增殖和迁移；白杨素、汉黄芩素、松属素和球松素查尔酮对AngⅡ诱导的VSMC迁移的抑制作用强于对其诱导的VSMC增殖的抑制作用。
