Garlic organic sulfides are dietary bioactive components with multiple biofunctions to prevent chronic diseases/inflammation and promote human health. DADS (diallyl disulfide), DATS (diallyl trisulfide), and DTS (diallyl tetrasulfide) are typical organic sulfides with similar structures from garlic. However, the structure-activity relationship of garlic organic sulfides remained unknown. The aim of the present study was to investigate the effect of DADS, DATS, and DTS on the gene expression profiling of human hepatocellular carcinoma cells (HepG2) by application of microarray and specialized analysis software, GO, Bio-Plex-based cytokines assay and IPA and analyze their structure-activity relationship according to antioxidant, anti-inflammatory, and metabolic-related properties. According to the microarray data, with the increase of S atom in garlic organic sulfides, its biological activity was gradually enhanced. In the general catalog of GO, garlic organic sulfides mainly affect biological process, molecular function, and cellular component. RT-qPCR results indicated that the microarray data is trustworthy, and the structure-activity analysis data found that more sulfur atoms have more powerful properties; thus, microarray data of DTS was preceded to the subsequent IPA analysis. The results of IPA analysis showed that the top 5 signaling pathways and molecular functions were disturbed by DTS; the molecular functions with the highest scores affected by DTS are cancer, cell apoptosis, and cell proliferation, which imply that the occurrence or metabolism of these diseases is related to the differential expression of the above-mentioned related genes and the activation of signaling channels, and the core of the most significant molecular network is inflammation. Finally, the results found that the secretions of 6 cytokines in macrophages were significantly inhibited by DTS treatment. This is the first study that analyzed the structure-activity relationship of garlic organic sulfides, which will provide useful genetic information for its multi-biofunction and promote their clinical application in the near future.

Glycolipid metabolic disorder is a serious threat to human health. Dark tea is a kind of traditional Chinese tea, which may regulate the glycolipid metabolic disorders. Dark tea extract (DTE) is the water extraction obtained from dark tea. Compared with traditional dark tea, DTE has the benefits of convenient consumption and greater potential for promoting health. However, the regulation of DTE on glycolipid metabolism and its molecular mechanism is rarely investigated. In our study, DTE was used as raw material to study the effect and molecular mechanism of its intervention on the glycolipid metabolic in db/db diabetic mice by using multiomics analysis and modern biological techniques. (1) DTE could significantly reduce fasting glucose in diabetic db/db mice, and the higher dose group has a better effect. Histopathological examination showed that DTE slightly improve the number of islets and decrease the number of islet β cells in the pancreatic tissue in db/db mice. (2) RNA-Seq was used to analyze the gene expression in liver tissue. In terms of biological processes, DTE mainly affected the inflammation and fatty acid metabolism. In terms of cell components, the lipoprotein and respiratory chain are mainly affected. In the aspect of molecular function, DTE mainly affected the redox related enzyme activity, iron ion binding and glutathione transferase. Arachidonic acid metabolism pathway, glutathione metabolism and PPAR signaling pathway were enriched by DTE with the results of KEGG pathway enrichment. In addition, real-time PCR results confirmed that DTE could significantly activate key genes of PPAR signaling pathway like Fabp1, Cyp4a1, Ehhadh, Cyp4a32, Aqp7 and Me1. (3) 16s rDNA showed that DTE could significantly decrease the ratio of Firmicutes/Bacteroidetes and the abundance of Proteobacteria, and increased the relative abundance of Verrucomicrobia at the phylum level. At the genus level, the relative abundance of Akkermansia, Prevotellaceae, Bacteroides and Alloprevotella was significantly increased after DTE treatment. This study provides multiomics molecular evidence for the intervention effect of DTE on abnormal glucose and lipid metabolism and the application of precise nutritional diet intervention of dark tea extract.