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Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.
Kuo, Huey-Liang; Chuang, Haw-Ling; Chen, Chang-Mu; Chen, Yu-Ya; Chen, Yu-Syuan; Lin, Ssu-Chia; Weng, Pei-Yu; Liu, Ting-Chun; Wang, Pei-Yun; Huang, Chun-Fa; Guan, Siao-Syun; Liu, Shing-Hwa; Yang, Shun-Fa; Wu, Cheng-Tien.
Afiliación
  • Kuo HL; School of Medicine, China Medical University, Taichung, 40402, Taiwan; Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40402, Taiwan; Clinical Nutrition, China Medical University Hospital, Taichung, 40402, Taiwan. Electronic address: 012307@tool.
  • Chuang HL; Department of Emergency, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427, Taiwan. Electronic address: tc2050403@tzuchi.com.tw.
  • Chen CM; Division of Neurosurgery, Department of Surgery, College of Medicine and Hospital, National Taiwan University, Taipei 10051, Taiwan. Electronic address: cmchen10@ntuh.gov.tw.
  • Chen YY; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC. Electronic address: u109076010@cmu.edu.tw.
  • Chen YS; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC. Electronic address: u108008441@cmu.edu.tw.
  • Lin SC; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC. Electronic address: cora20001017@gmail.com.
  • Weng PY; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC. Electronic address: zxc0963511081@gmail.com.
  • Liu TC; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC. Electronic address: t3129t3129@gmail.com.
  • Wang PY; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC. Electronic address: lllll520520@gmail.com.
  • Huang CF; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; Department of Nursing, College of Medical and Health Science, Asia University, Taichung, 413, Taiwan. Electronic address: cfhuang@mail.cmu.edu.tw.
  • Guan SS; Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 32546, Taiwan. Electronic address: ssguan@iner.gov.tw.
  • Liu SH; Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. Electronic address: shingwaliu@ntu.edu.tw.
  • Yang SF; Institute of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan. Electronic address: ysf@csmu.edu.tw.
  • Wu CT; Department of Nutrition, China Medical University, Taichung, Taiwan, 40402, ROC; Master Program of Food and Drug Safety, China Medical University, Taichung, 406040, Taiwan. Electronic address: ct-wu@mail.cmu.edu.tw.
Eur J Pharmacol ; 977: 176676, 2024 Aug 15.
Article en En | MEDLINE | ID: mdl-38815787
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-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-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-ß), 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obstrucción Ureteral / Fibrosis / Apoptosis / Flavanonas / Modelos Animales de Enfermedad / Estrés del Retículo Endoplásmico / Chaperón BiP del Retículo Endoplásmico Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obstrucción Ureteral / Fibrosis / Apoptosis / Flavanonas / Modelos Animales de Enfermedad / Estrés del Retículo Endoplásmico / Chaperón BiP del Retículo Endoplásmico Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos