Natural products are small molecules naturally produced by multiple sources such as plants, animals, fungi, bacteria and archaea. They exert both beneficial and detrimental effects by modulating biological targets and pathways involved in oxidative stress and antioxidant response. Natural products’ oxidative or antioxidative properties are usually investigated in preclinical experimental models, including virtual computing simulations, cell and tissue cultures, rodent and nonhuman primate animal models, and human studies. Due to the renewal of the concept of experimental animals, especially the popularization of alternative 3R methods for reduction, replacement and refinement, many assessment experiments have been carried out in new alternative models. The model organism Caenorhabditis elegans has been used for medical research since Sydney Brenner revealed its genetics in 1974 and has been introduced into pharmacology and toxicology in the past two decades. The data from C. elegans have been satisfactorily correlated with traditional experimental models. In this review, we summarize the advantages of C. elegans in assessing oxidative and antioxidative properties of natural products and introduce methods to construct an oxidative damage model in C. elegans. The biomarkers and signaling pathways involved in the oxidative stress of C. elegans are summarized, as well as the oxidation and antioxidation in target organs of the muscle, nervous, digestive and reproductive systems. This review provides an overview of the oxidative and antioxidative properties of natural products based on the model organism C. elegans.

Humantenine, an alkaloid isolated from the medicinal herb Gelsemium elegans (Gardner & Chapm.) Benth., has been reported to induce intestinal irritation, but the underlying toxicological mechanisms remain unclear. The object of the present study was to investigate the RNA N6-methyladenosine (m6A) modification and distinct mRNA transcriptome profiles in humantenine-treated HCT116 human colon cancer cells. High-throughput MeRIP-seq and mRNA-seq were performed, and bioinformatic analysis was performed to reveal the role of abnormal RNA m6A modification and mRNA expression in humantenine-induced intestinal cell toxicity. After humantenine treatment of HCT116 cells, 1401 genes were in the overlap of differentially m6A-modified mRNA and differentially expressed mRNA. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology annotation terms for actin cytoskeleton, tight junctions, and adherens junctions were enriched. A total of 11 kinds of RNA m6A methylation regulators were differentially expressed. The m6A methylation levels of target genes were disordered in the humantenine group. In conclusion, this study suggested that the HCT116 cell injury induced by humantenine was associated with the abnormal mRNA expression of m6A regulators, as well as disordered m6A methylation levels of target genes.