ABSTRACT
Objective To make a preliminary investigation on the mechanism of the glycyrrhizin flavonoids alleviating the gastrointestinal toxicities of irinotecan. The pharmacological effects of glycyrrhizin flavonoids on the changes of endogenous differential metabolites of irinotecan-induced gastrointestinal toxicities were evaluated by using GC-MS metabolomics methods. Methods C57BL/6 mice were divided into normal group, model group, positive group (ciprofloxacin), and glycyrrhizin flavonoids group. Irinotecan induced colitis model were established in mice by intraperitoneally injected. The body weight, length of colon, and tissue sections were used to evaluate the effect of glycyrrhizin flavonoids on alleviating irinotecan-induced experimental colitis. Meanwhile, to evaluate the attenuating effect of glycyrrhizin flavonoids from the perspective of metabonomics, GC-MS was used for non-targeted metabolism in order to find out the the change of related metabolites in plasma between experimental colitis mice and glycyrrhizin flavonoids treatment mice. Furthermore, metabolic pathway was constructed by MetaboAnalyst software to explore the potential mechanism. Results Glycyrrhizin flavonoids could significantly reduce the loss of body weight, colon shortening, and intestinal damage caused by irinotecan administration, and effectively reverse the irinotecan-induced plasma metabolic disorders in mice, including fatty acid metabolism, amino acid metabolism and carbohydrate metabolism, significantly callback seven long-chain fatty acids such as lauric acid, palmitic acid, linoleic acid, oleic acid, linolenic acid, palmitic acid monoglyceride, and oleic acid monoglyceride. Conclusion Glycyrrhizin flavonoids could improve the irinotecan-induced experimental colitis in mice by regulating linoleic acid metabolism and alpha-linolenic acid metabolism.
ABSTRACT
Irinotecan was a commonly used chemotherapeutic drug for treating colorectal cancer recurrence and deterioration. Despite its good efficacy, gastrointestinal toxicities such as delayed-onset diarrhea, nausea, and vomiting have severely restrained its clinical application. Recent studies have suggested that the gastrointestinal toxicities of irinotecan were closely related to its metabolism in microbiota-gut-liver axis and the associated bile acid and tryptophan metabolic disturbance. Therefore, this review was mainly focused on the relationship between the disturbed metabolism of endogenous and gastrointestinal toxicities of irinotecan. What’s more, in order to provide reference for further study and development of related drugs, the effect of Chinese materia medica in intervention and treatment of irinotecan-induced gastrointestinal toxicity have also been discussed.