Effect of Tianhuang Formula on Renal Injury and Fibrosis in Hyperuricemia Mice
10.13422/j.cnki.syfjx.20230511
- VernacularTitle:田黄方对高尿酸血症小鼠肾损伤及纤维化的作用
- Author:
Juxian MO
1
;
Kaireng WU
2
;
Minghui LI
3
;
Zhe CHEN
2
;
Tian LAN
1
;
Wei XIAO
1
;
Jiao GUO
1
Author Information
1. Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine， Key Laboratory of Glucolipid Metabolic Disorder， Ministry of Education； Guangdong Traditional Chinese Medicine（TCM） Key Laboratory for Metabolic Diseases， Institute of Chinese Medicine， Guangdong Pharmaceutical University， Guangzhou 510006， China
2. School of Pharmacy， Guangdong Pharmaceutical University， Guangzhou 510006， China
3. School of TCM， Guangdong Pharmaceutical University， Guangzhou 510006， China
- Publication Type:Journal Article
- Keywords:
Tianhuang formula;
hyperuricemia nephropathy;
network pharmacology;
renal injury;
inflammation;
fibrosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(11):72-81
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the protective effect and mechanism of Tianhuang formula (THF) against renal injury in hyperuricemia nephropathy (HN) mice through network pharmacology. MethodAll mice were randomly divided into a normal group, a model group, a febuxostat group (5 mg·kg-1), a low-dose THF group (L-THF, 60 mg·kg-1), and a high-dose THF group (H-THF, 120 mg·kg-1). The mice in the normal group were treated with 0.5% sodium carboxymethylcellulose (CMC-Na) by gavage daily. The HN model was induced by oral administration of 500 mg·kg-1 hypoxanthine and intraperitoneal injection of 200 mg·kg-1 oteracil potassium in mice except for those in the blank group. The mice in the groups with drug intervention were treated with corresponding drugs by gavage for three weeks. The levels of serum uric acid, creatinine, urea nitrogen, and 24-h albuminuria were measured. The renal injury was observed by hematoxylin-eosin (HE) staining and PAS staining, and renal fibrosis was observed by Sirius red staining. The effects and molecular mechanism of THF in HN mice were analyzed by Western blot, network pharmacology, and molecular docking. ResultBiochemical results indicated that compared with model group, BUN and 24 h urinary protein levels were significantly decreased in L-THF group (P<0.05), SUA and SCr levels were significantly decreased (P<0.01), and SUA, BUN, SCr and 24 h urinary protein levels in H-THF group were significantly decreased (P<0.01). The results of pathological staining showed that the kidney injury and interstitial fibrosis were improved in different doses of THF groups (P<0.05). Western blot results showed that the Nod-like receptor heat protein domain associated protein 3 (NLRP3) inflammatorome, interleukin-1β (IL-1β), fibronectin (FN), uric acid transporter 1 (URAT1), phosphorylated p65 (p-p65) and phosphorylated nuclear transcription factor (NF) -κB were inhibited in the H-THF group The expression of protein-producing α (p-IκBα) was reduced to the normal level (P<0.01), but the expression of IL-1β, URAT1 and p-IκBα in HN mice was not affected in the L-THF group. ConclusionTHF ameliorates renal inflammation and fibrosis by inhibiting the activation of NF-κB and NLRP3 inflammasomes to alleviate HN
