Comparative metabolomics reveals the cytotoxic and anti-inflammatory discriminatory chemical markers of raw and roasted colocynth fruit ( Citrullus colocynthis L.).

Colocynth has a long history of use in traditional medicine for treatment of various inflammatory diseases where it is commonly roasted before being applied for medical purposes to reduce its toxicity. This study aims at tracking the effect of heat processing on the metabolic profile of the peels, pulps and seeds of colocynth fruit using UPLC-QqQ-MS-based metabolomics. The analysis resulted in tentative identification of 72 compounds belonging to different chemical classes. With roasting, a decline was observed in the relative amounts of chemical constituents where 42, 25 and 29 compounds were down-regulated in the peels, pulps and seeds, respectively. EC 100 values resulting in 100% cell viability were all higher in roasted samples compared to their relevant raw ones. Correlation analysis indicated that the main cytotoxic chemical markers were cucurbitacin glycosides and their genins. Further, ex vivo anti-inflammatory activity testing multivariate models revealed that unprocessed samples correlated with inhibition of TNF-α, IL-1β and IFN-γ where quercetrin, calodendroside A, and hexanoic acid methyl ester were the most significant chemical markers, while processed samples showed correlation with IL-6 pro-inflammatory marker inhibition with protocatechuic and protocatechuic acid glycoside being the main correlated chemical markers.