Chemical characterization of a renoprotective metabolite from termite-associated Streptomyces sp. RB1 against cisplatin-induced cytotoxicity

Abstract

Platinum-based anticancer drug therapies can cause renal damage and apoptotic kidney cell damage. The development of reno- and kidney-protective molecules is therefore urgently required. To address this challenge, we explored secondary metabolites of termite-associated Streptomyces sp. RB1 isolated fromthe cuticle of the South African termite,Macrotermes natalensis for their renoprotective ability using bioassay-guided fractionation and LLC-PK1 cells. Chemical investigation of the MeOH extract of Streptomyces sp. RB1 resulted in the isolation and identification of a renoprotectivemetabolite, 1-O-(2-aminobenzoyl)-α-L-rhamnopyranoside (ABR) (1) from the active fraction, which ameliorated cisplatin-induced cytotoxicity to 80% of the control value at 25 µM. Upregulated phosphorylation of c-Jun N-terminal kinases (JNK) and p38 following cisplatin treatment was markedly decreased after pre-treatment of cells with ABR. In addition, levels of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after pre-treatment with ABR. These findings provide experimental evidence that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of ABR, which may inspire the development of novel therapeutic substances to prevent anticancer drug-induced nephrotoxicity.