AUTHOR=Li Guozheng , Guan Chen , Xu Lingyu , Wang Lin , Yang Chengyu , Zhao Long , Zhou Bin , Luo Congjuan , Luan Hong , Jiang Wei , Li Chenyu , Xu Yan TITLE=Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice JOURNAL=Frontiers in Pharmacology VOLUME=Volume 11 - 2020 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.584942 DOI=10.3389/fphar.2020.584942 ISSN=1663-9812 ABSTRACT=Considerable evidences have indicated that the elevated uric acid (UA) was involved in renal tubular injury leading to hyperuricemic nephropathy (HN). Scutellarin is a biologically active flavonoid derived from 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 decreased in renal function with the increased SCr and BUN (P < 0.05). HE staining results showed a histological injury in HN mice kidney tissues with severe tubular damage. Scutellarin dose-dependently alleviated the renal injury of HN model (P < 0.05), and a dose of 20 mg/kg/day remarkably reduced Scr level (26.10 ± 3.23 μmol/mL vs. 48.39 ± 7.51 μmol/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 the NGAL, Kim-1, Cystatin C and IL-18 protein expression levels in HN mouse (P< 0.05). Overexpressed CCN1 could not induce the 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.