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Catalpol alleviates adriamycin-induced nephropathy by activating the SIRT1 signalling pathway in vivo and in vitro.
- Source :
-
British Journal of Pharmacology . Dec2019, Vol. 176 Issue 23, p4558-4573. 16p. 2 Diagrams, 1 Chart, 7 Graphs. - Publication Year :
- 2019
-
Abstract
- <bold>Background and Purpose: </bold>Catalpol, a water-soluble active ingredient isolated from Rehmannia glutinosa, exhibits multiple pharmacological activities. However, the mechanism(s) underlying protection against renal injury by catalpol remains unknown.<bold>Experimental Approach: </bold>Adriamycin-induced kidney injury models associated with podocyte damage were employed to investigate the nephroprotective effects of catalpol. In vivo, TUNEL and haematoxylin-eosin staining was used to evaluate the effect of catalpol on kidney injury in mice. In vitro, effects of catalpol on podocyte damage induced by adriamycin was determined by elisa kit, flow cytometry, Hoechst 33342, and TUNEL staining. The mechanism was investigated by siRNA, EX527, and docking simulations.<bold>Key Results: </bold>In vivo, catalpol treatment significantly improved adriamycin-induced kidney pathological changes and decreased the number of apoptotic cells. In vitro, catalpol markedly decreased the intracellular accumulation of adriamycin and reduced the calcium ion level in podocytes and then attenuated apoptosis. Importantly, the regulatory effects of catalpol on sirtuin 1 (SIRT1), multidrug resistance-associated protein 2 (MRP2), and the TRPC6 channel were mostly abolished after incubation with SIRT1 siRNA or the SIRT1-specific inhibitor EX527. Furthermore, docking simulations showed that catalpol efficiently oriented itself in the active site of SIRT1, indicating a higher total binding affinity score than that of other SIRT1 activators, such as resveratrol, SRT2104, and quercetin.<bold>Conclusion and Implications: </bold>Taken together, our results suggest that catalpol exhibits strong protective effects against adriamycin-induced nephropathy by inducing SIRT1-mediated inhibition of TRPC6 expression and enhancing MRP2 expression. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MULTIDRUG resistance-associated proteins
*KIDNEY diseases
*QUERCETIN
*CALCIUM ions
*KIDNEY injuries
*DOXORUBICIN
*RESVERATROL
*RESEARCH
*CELL culture
*ANIMAL experimentation
*ORAL drug administration
*RESEARCH methodology
*GLYCOSIDES
*APOPTOSIS
*CELL physiology
*EVALUATION research
*MEDICAL cooperation
*PREVENTIVE health services
*CELLULAR signal transduction
*PLANTS
*COMPARATIVE studies
*TRANSFERASES
*RESEARCH funding
*ACUTE kidney failure
*MICE
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 176
- Issue :
- 23
- Database :
- Academic Search Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 140851027
- Full Text :
- https://doi.org/10.1111/bph.14822