Multi-omics studies show that naringin improves cyclophosphamide-induced testicular and intestinal damage by enhancing energy metabolism.

Abstract

Cyclophosphamide (CTX) is an anticancer agent that severely impairs male reproductive health. Naringin (NAR), a flavonoid compound, has the potential to ameliorate CTX-induced damage; however, the underlying mechanisms remain unclear. In this study, an integrative approach combining transcriptomics, microbiome analysis, and serum metabolomics was employed to comprehensively evaluate the protective effects of NAR on reproductive function in CTX-treated mice. Microbiome analysis revealed that NAR restored CTX-induced alterations in gut microbial composition. Metabolomic profiling demonstrated that NAR stabilised cholesterol metabolism and primary bile acid biosynthesis, increased serum choline levels, and alleviated reproductive dysfunction in CTX-exposed mice. Transcriptomic analyses of the testes and intestine indicated that NAR modulated glycolysis and the MAPK signalling pathway in CTX-treated mice. Validation of serum metabolites further supported their role in promoting intestinal and testicular development. Research indicates that naringin ameliorates cyclophosphamide-induced reproductive risks in males, partly due to its enhancement of energy metabolism.

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