Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice

Li, Guozheng; Guan, Chen; Xu, Lingyu; Wang, Lin; Yang, Chengyu; Zhao, Long; Zhou, Bin; Luo, Congjuan; Luan, Hong; Jiang, Wei; Li, Chenyu und Xu, Yan (22. Oktober 2020): Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice. In: Frontiers in Pharmacology, Bd. 11, 584942: S. 1-12

Abstract

Considerable evidences have indicated that elevated uric acid (UA) was involved in renal tubular injury leading to hyperuricemic nephropathy (HN). Scutellarin is a biologically active flavonoid derived from the Chinese traditional herb Erigeron breviscapus Hand-Mazz, which has been widely used in the treatment of cardiovascular and cerebrovascular diseases. In the present study, we analyzed the effect of scutellarin on HN, by using C57BL/6 mice and human renal tubular epithelial cell line HK-2 which was subjected to adenine/potassium oxonate and UA to mimic a HN injury. The HN mice showed a significant decrease in renal function with the increased SCr and blood urea nitrogen (BUN) (p < 0.05). Hematoxylin-eosin staining results showed a histological injury in HN mice kidney tissues with severe tubular damage. Scutellarin dose dependently alleviated the renal injury of the HN model (p < 0.05), and a dose of 20 mg/kg/day remarkably reduced the Scr level (26.10 +/- 3.23 mu mol/ml vs. 48.39 +/- 7.51 mu mol/ml, p < 0.05) and BUN (151.12 +/- 30.24 mmol/L vs. 210.43 +/- 45.67 mmol/L, p < 0.05) compared with the HN model group. Similarly, scutellarin decreased NGAL, Kim-1, cystatin C, and IL-18 protein expression levels in HN mouse (p < 0.05). Overexpressed CCN1 could not induce NLRP3 inflammasome activation, with no change of mRNA and protein expression levels of NLRP3, ASC, and pro-caspase-1 compared with the control HK-2. However, HK-2 showed a significant NLRP3 inflammasome activation and apoptosis. Importantly, knockdown of CCN1 not only aggravated NLRP3 inflammasome activation and apoptosis but also abrogated the protective effect of scutellarin in UA-induced HK-2 injury. Thus, scutellarin might alleviate HN progression via a mechanism involved in CCN1 regulation on NLRP3 inflammasome activation.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Keywords: Scutellarin; hyperuricemia; hyperuricemic nephropathy; CCN1; NLRP3 inflammasome
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1663-9812
• Sprache: Englisch