Penjai ThongnuanjanSirima SoodvilaiSomsak FongsupaNapason ChabangPornpun VivithanapornPatoomratana TuchindaSunhapas SoodvilaiRangsit UniversityFaculty of Medicine Ramathibodi Hospital, Mahidol UniversityMahidol UniversityThammasat University2022-08-042022-08-042021-06-01Biological and Pharmaceutical Bulletin. Vol.44, No.6 (2021), 830-83713475215091861582-s2.0-85107194643https://repository.li.mahidol.ac.th/handle/123456789/78959Background: Cisplatin is an effective chemotherapy but its main side effect, acute kidney injury, limits its use. Panduratin A, a bioactive compound extracted from Boesenbergia rotunda, shows several biological activities such as anti-oxidative effects. The present study investigated the nephroprotective effect of panduratin A on cisplatin-induced renal injury. Methods: We investigated the effect of panduratin A on the toxicity of cisplatin in both mice and human renal cell cultures using RPTEC/TERT1 cells. Results: The results demonstrated that panduratin A ameliorates cisplatin-induced renal toxicity in both mice and RPTEC/ TERT1 cells by reducing apoptosis. Mice treated with a single intraperitoneal (i.p.) injection of cisplatin (20mg/kg body weight (BW)) exhibited renal tubule injury and impaired kidney function as shown by histological examination and increased serum creatinine. Co-administration of panduratin A (50mg/kg BW) orally improved kidney function and ameliorated renal tubule injury of cisplatin by inhibiting activation of extracellular signal-regulated kinase (ERK)1/2 and caspase 3. In human renal proximal tubular cells, cisplatin induced cell apoptosis by activating pro-apoptotic proteins (ERK1/2 and caspase 3), and reducing the anti-apoptotic protein (Bcl-2). These effects were significantly ameliorated by co-treatment with panduratin A. Interestingly, panduratin A did not alter intracellular accumulation of cisplatin. It did not alter the anticancer efficacy of cisplatin in either human colon or non-small cell lung cancer cell lines. Conclusions: The present study highlights panduratin A has a potential protective effect on cisplatin’s nephrotoxicity.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1248/bpb.b21-00036