title: Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity.
abstract: 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 μM. 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seulah
authors.initials: S
authors.lastname: Lee
authors.affiliation: Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Seongnam 13488, Republic of Korea.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Jung
authors.affiliation: College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
authors.forename: Dahae
authors.initials: D
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seoung Rak
authors.initials: SR
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Kang Ro
authors.initials: KR
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea. Electronic address: kkang@gachon.ac.kr.
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: khkim83@skku.edu.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000633:toxicity; D029768:Cornus / Q000737:chemistry*; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D012015:Reference Standards; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology; D053978:Pentacyclic Triterpenes
chemical_list: D002945:Cisplatin; D018696:Neuroprotective Agents; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes
keywords: Caspase-3; Cornus walteri; MAPKs; Nephrotoxicity; Triterpenoid