Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 25, Issue 23, Pages 5613-5618Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2015.10.035
Keywords
Cornus walteri; Triterpenoid; Nephrotoxicity; MAPKs; Caspase-3
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2015R1C1A1A02037383]
- R&D program research grants of Jeollabuk-Do, Republic of Korea
- R&D program research grants of Imsil-Gun, Republic of Korea
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The present study reports a renoprotective effect and the mechanism of action of lupane triterpenes isolated from Cornus walteri in cisplatin-induced renal toxicity. A phytochemical investigation of the MeOH extract of the stems and stem bark of C. walteri resulted in the isolation and identification of twelve lupane triterpenes. Among these, betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125 mu M. Upregulated phosphorylation of JNK, ERK, and p38 following cisplatin treatment were markedly decreased after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. In addition, the protein expression level of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after co-treatment with betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol. These results show that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of betulinic acid, 29-oxobetulinic acid, betulin 3-acetate, and lupeol isolated from C. walteri extract. (C) 2015 Elsevier Ltd. All rights reserved.
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