Chemical Profiling of Citrus sinensis Root and the Effects of Its Secondary Metabolites on Cisplatin-Induced Renal and Cardiac Toxicities

Citrus fruits are among the most important economical crops, because of their nutritional value, medicinal importance, and unique flavor. Gas liquid chromatography-mass spectrometry of the hydro-distilled oil from the root resulted in the identification of 110 compounds with germacrene B (22%), aromadendrene (21.6%), alpha-santalene (7.1%), geijerene (4,81%), germacrene D (4.3%), and limonene (3.4%) as major constituents. In addition, chemical profiling the dichloromethane fraction of the root analyzed by high-performance liquid chromatography-photo diode array detector-electrospray tandem mass spectrometry afforded the identification of 43 compounds belonging to acridone alkaloids, coumarins, and flavonoids. Moreover, xanthyletin, citracridone I and II, clausarin, O-methylcitrusinine-I, and grandisinine were isolated as major metabolites using column chromatography and characterized depending on different spectroscopic techniques. Xanthyletin and citracridone I were investigated for their in vitro cytotoxicity against hepatocellular carcinoma and breast adenocarcinoma cell lines, and in vivo protective effect against cisplatin-induced nephrotoxicity and cardiotoxicity in different dose levels in a rat model. Xanthyletin and citracridone I showed protective activity against cisplatin-induced nephrotoxicity. It attenuated cisplatin-induced elevation of both serum urea and creatinine in a dose-dependent manner. Moreover, xanthyletin attenuated cisplatin-induced elevation of malondialdehyde and glutathione in both renal and cardiac tissues.

Automated summary

Citrus fruits are economically important due to their nutrition value, medicinal importance, and unique flavor. The oil extracted from the roots contains compounds such as aromadendrene, germacrene B, and limonene. Chemical analysis of the roots also revealed the presence of acridone alkaloids, coumarins, and flavonoids. Xanthyletin and citracridone I showed protective effects against cisplatin-induced nephrotoxicity and elevated levels of malondialdehyde and glutathione in renal and cardiac tissues.