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 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 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.
Highlights
Hyperuricemia (HUA), a common metabolic disorder of purine, is characterized by high serum uric acid (SUA)-precipitated urate crystals in both the kidneys and joints
Scutellarin possesses strong anti-inflammatory activities in many disease (Wang W. et al, 2016; Zhao et al, 2016; Liu et al, 2017) but remains elusive whether this agent had any potential effects on hyperuricemic nephropathy (HN), which, had been involved in various inflammatory conditions ranging from Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation to apoptosis
Our study confirmed that scutellarin significantly inhibited NLRP3 inflammasome activation and apoptosis in mice and HK-2 cells induced by UA, unraveling a previously unappreciated action mechanism for scutellarin in preventing NLRP3 inflammasome activation and apoptosis in UA-induced kidney tissues and renal tubular epithelial cell injury
Summary
Hyperuricemia (HUA), a common metabolic disorder of purine, is characterized by high serum uric acid (SUA)-precipitated urate crystals in both the kidneys and joints. Elevated SUA may cause the formation of monosodium urate crystals in connective tissues, eventually leading to gout. Numerous studies revealed that elevated uric acid (UA) was associated with renal tubular injury and subsequent tubulointerstitial fibrosis, causing hyperuricemic nephropathy (HN), which can eventually cause CKD. Current studies revealed that activation of NLRP3 inflammasome can be triggered by soluble UA and UA crystals, causing maturation of pro-inflammatory cytokines like IL-1β and leading to congenital immune defense against danger signals such as infection and metabolic disorder (Isaka et al, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
