Withaferin A protects against endoplasmic reticulum stress-associated apoptosis, inflammation, and fibrosis in the kidney of a mouse model of unilateral ureteral obstruction
| Autor: | Yao Pang Chung, Chia Hung Liu, Chang-Mu Chen, Chen Tien Wu, Kuo Tong Huang, Siao Syun Guan, Chih-Kang Chiang, Shing-Hwa Liu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Pharmaceutical Science Tetrazoles Apoptosis Pharmacology urologic and male genital diseases Kidney chemistry.chemical_compound 0302 clinical medicine Fibrosis Drug Discovery Endoplasmic Reticulum Chaperone BiP 0303 health sciences Nephritis biology Endoplasmic Reticulum Stress female genital diseases and pregnancy complications medicine.anatomical_structure 030220 oncology & carcinogenesis Molecular Medicine medicine.symptom medicine.drug Signal Transduction Ureteral Obstruction Inflammation Withania somnifera Protective Agents 03 medical and health sciences medicine Renal fibrosis Animals Renal Insufficiency Chronic Withanolides 030304 developmental biology business.industry Biphenyl Compounds biology.organism_classification medicine.disease Mice Inbred C57BL Candesartan Disease Models Animal Complementary and alternative medicine chemistry Withaferin A Benzimidazoles business Kidney disease |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 79 |
| ISSN: | 1618-095X |
| Popis: | Background Withaferin A is a functional ingredient of a traditional medicinal plant, Withania somnifera, which has been broadly used in India for protecting against chronic diseases. This bioactive steroidal lactone possesses multiple functions such as anti-oxidation, anti-inflammation, and immunomodulation. Chronic kidney disease (CKD) is one of the major health problems worldwide with the high complication, morbidity, and mortality rates. The detailed effects and underlying mechanisms of withaferin A on CKD progression still remain to be clarified. Purpose We aimed to investigate whether withaferin A treatment ameliorates the development of renal fibrosis and its related mechanisms in a CKD mouse model. Methods A mouse model of unilateral ureteral obstruction (UUO) was used to mimic the progression of CKD. Male adult C57BL/6J mice were orally administered with 3 mg/kg/day withaferin A for 14 consecutive days after UUO surgery. Candesartan (5 mg/kg/day) was used as a positive control. Results Both Withaferin A and candesartan treatments significantly ameliorated the histopathological changes and collagen deposition in the UUO kidneys. Withaferin A could significantly reverse the increases in the protein levels of pro-fibrotic factors (fibronectin, transforming growth factor-β, and α-smooth muscle actin), inflammatory signaling molecules (phosphorylated nuclear factor-κB-p65, interleukin-1β, and cyclooxygenase-2), and cleaved caspase-3, apoptosis, and infiltration of neutrophils in the UUO kidneys. The protein levels of endoplasmic reticulum (ER) stress-associated molecules (GRP78, GRP94, ATF4, CHOP, phosphorylated eIF2α, and cleaved caspase 12) were increased in the kidneys of UUO mice, which could be significantly reversed by withaferin A treatment. Conclusion Withaferin A protects against the CKD progression that is, at least in part, associated with the moderation of ER stress-related apoptosis, inflammation, and fibrosis in the kidneys of CKD. Withaferin A may serve as a potential therapeutic agent for the development of CKD. |
| Databáze: | OpenAIRE |
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