Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.
Journal
European journal of pharmacology
Series/Report No.
European Journal of Pharmacology
Journal Volume
977
Start Page
176676
ISSN
1879-0712
Date Issued
2024-08-15
Author(s)
Kuo, Huey-Liang
Chuang, Haw-Ling
Chen, Yu-Ya
Chen, Yu-Syuan
Lin, Ssu-Chia
Weng, Pei-Yu
Liu, Ting-Chun
Wang, Pei-Yun
Huang, Chun-Fa
Guan, Siao-Syun
Yang, Shun-Fa
Wu, Cheng-Tien
DOI
10.1016/j.ejphar.2024.176676
Abstract
Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-β) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-β-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-β), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.
Subjects
Chronic kidney disease
ER stress
Fibrosis
Inflammation
Wogonin
SDGs
Publisher
Elsevier B.V.
Type
journal article