Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.584942
Keywords
scutellarin; hyperuricemia; hyperuricemic nephropathy; CCN1; NLRP3 inflammasome
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Funding
- National Natural Science Foundation of China [81470973, 81770679, 81970582]
- Qingdao Municipal Science and Technology Bureau [20-3-4-36nsh]
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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.
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