Identification and mechanism of action of renoprotective constituents from peat moss Sphagnum palustre in cisplatin-induced nephrotoxicity

In search for bioactive constituents from natural resources, the ethanol (EtOH) extract of Sphagnum palustre showed significant renoprotective effects against cisplatin-induced damage in kidney cells. Phytochemical investigation of the EtOH extract led to the identification of a new flavonoid, 6-methyl-(2R,35)-alpinone, along with six known flavonoids, four steroids, six triperpenoids, and three fatty acids. Among them, ergosterol peroxide, (3 beta,22E,24S)-3-hydroxy-ergosta-5,22-dien-7-one, and betulinic acid ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 125, 125 and 50 mu M, respectively. Moreover, the elevated percentage of apoptotic cells by cisplatin was significantly reduced after co-treatment with the EtOH extract of S. palustre and ergosterol peroxide, (3 beta,22E,24S)-3-hydroxy-ergosta-5,22-dien-7-one, and betulinic acid. Upregulated phosphorylation of INK and p38 by cisplatin treatment was markedly decreased after co-treatment with ergosterol peroxide, (3 beta,22E,24S)-3-hydroxy-ergosta-5,22-dien-7-one, and betulinic acid. These results show that blocking the MAPKs signalling cascade plays a critical role in mediating the renoprotective effect of S. palustre. (C) 2015 Elsevier Ltd. All rights reserved.