ABSTRACT
Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.
Subject(s)
Emodin , Fibrosis , Mitochondria , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Renal Insufficiency, Chronic , Animals , Emodin/pharmacology , Emodin/therapeutic use , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Fibrosis/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism , Male , Rats , Rats, Sprague-Dawley , Homeostasis/drug effects , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Ureteral Obstruction/pathology , Ureteral Obstruction/drug therapy , Transforming Growth Factor beta1/metabolism , Cell LineABSTRACT
Nonylphenol is an endocrine disrupting chemicals that can disrupt the organisms' reproductive system, and exists widely in rivers and lakes. Lycium barbarum polysaccharide (LBP) is the main active constituent (about 10%) in Lycium barbarum, which is used to protect reproductive health. In this study, we investigated whether LBP can alleviate nonylphenol exposure induced testicular injury in juvenile zebrafish. We detected histological alteration, anti-oxidant enzyme profile and P450 gene transcription to assess LBP effect on testicular development. The GSI reduced significantly due to nonylphenol exposure, while LBP can improve the GSI. The densities of sperms increased and non-celluar zone decreased after LBP treatment. Meanwhile, Cyp11b gene was up regulated to NP group, and cyp19a gene was down regulated to NP group. In sum, the LBP could repair the testicular injury in zebrafish. This findings provide a basis research to remit the estrogen effect of artificial endocrine disruptor.
