Phlorizin isolated from seagrass Syringodium isoetifolium inhibits diethylnitrosamine and carbon tetrachloride-induced hepatocellular carcinoma in BALB/c mice

Abstract

Marine-derived natural products are secondary metabolites widely used for various therapeutic applications. The present study was carried out to isolate the bioactive compound from seagrass Syringodium isoetifolium and explored the in vitro, in silico and in vivo anticancer activity against hepatocellular carcinoma. The bioactive compound was isolated from an aqueous ethanol extract of S. isoetifolium by column chromatography. The in vitro anticancer effect of the isolated compound was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Acridine Orange/Ethidium Bromide (AO/EtBr), DNA fragmentation, flow cytometry and western blotting against HepG2 cell lines. The molecular docking and diethylnitrosamine and carbon tetrachloride-induced hepatocellular carcinoma in BALB/c mice were also done. Liver morphology, hematological and biochemical parameters and histopathological examination were also performed in the present work. The structure of the isolated compound was confirmed by 1H NMR, 13C NMR, FT-IR and mass spectral data. The in vitro anticancer activity confirmed the occurrence of apoptosis in isolated phlorizin-treated HepG2 cells. Docking studies of the isolated compound into the binding site of NAD+-dependent deacetylase showed a better binding cavity against SIRT3 protein. The in vivo anticancer activity of phlorizin significantly reduced the malignant tumor and normalized the hematological and biochemical parameters. The histopathological examination of DEN+CCl4-induced HCC mice reveals promising anticancer activity. The present study concluded that the isolated compound of phlorizin from Syringodium isoetifolium had potential anticancer activity against hepatocellular carcinoma.