Ginsenoside Rg1 is one of the major ginsenosides found in roots of Panax ginseng and Panax notoginseng. Ginsenoside Rg1 is known to possess various biological activities including immunity enhancement activity. However, it is not clear whether the regulation of immune function by Rg1 is related to the intestinal microbiota. In the present study, the immuno-modulatory and gut microbiota-reshaping effects of ginsenoside Rg1 were evaluated. Ginsenoside Rg1 acts as an immune-enhancing agent to increase spleen index and the number of T, B and dendritic cells in dexamethasone (Dex)-treated mice. Ginsenoside Rg1 also increased the production of sIgA and regulated the expression of interleukin 2 (IL-2), IL-4, IL-10 and IFN-γ. Meanwhile, Rg1 administration regulated the structure of intestinal microbiota. The relative abundance of mouse intestinal microbial groups, such as Alistipes, Ruminococcaceae, Lachnospiraceae, and Roseburia were increased by Rg1 administration, whereas a decrease in the potential pathogens like Helicobacteraceae, Dubosiella, Mycoplasma, Alloprevotella, Allobaculum was observed. Moreover, Rg1 metabolites of Lachnospiraceae bacterium enhanced the proliferation of CD4⁺ T cells and T regulatory (Treg) cells. Ginsenoside Rg1 improved the inflammatory condition of the colonic tissue and repaired the destructed mucosal barrier. This study suggested that Rg1 strengthens immunity with regulating the homeostasis of intestinal microbiota in mice.

Type 2 diabetes mellitus (T2DM) has developed into an important health concern worldwide. The discovery of phlorotannins and their efficacy in the treatment of T2DM has become a hotspot for research in various fields. In this study, the potential phlorotannins and mechanism of six brown algae against T2DM were in-depth investigated using biological activity assays, LC-MS, and network pharmacology. First, the ethyl acetate fraction (EA frac.) showed high polyphenolic content and possessed significantly antioxidant and enzyme inhibitory abilities. Further, a total of fifty-nine peaks were obtained from six EA fracs. via UPLC-QE-MS/MS analysis, and fifteen of them were identified as phlorotannins and their isomers or derivatives. In detail, the chemical structures of six phlorotannins were inferred as dibenzodioxine-1,3,6,8-tetraol, bifuhalol, dioxinodehydroeckol, eckol, fucofurodiphlorethol, and fucotriphlorethol; three phlorotannin isomers were deduced to be fucophlorethol, trifucol, triphlorethol A, or triphlorethol B; and the phlorotannin derivative of m/z 263 was determined to be dibenzodioxine-1,2,3,6,8-pentanol or dibenzodioxine-1,2,4,5,7-pentanol. Moreover, 43 T2DM-related targets acted on by these chemicals were identified, and the function of phlorotannin to prevent and treat T2DM was elucidated in a holistic way based on the established compound-target-disease network, and GO function and KEGG pathway enrichment analysis.

Cannabis sativa L. (cannabis) is a medicinal plant and has been used for many years for the treatment of epilepsy (EP), which is a common neurological disease. This study aimed to investigate the mechanism of cannabis action in EP, with emphasis on the leading compounds, targets and pathways. In this study, systematic pharmacology and bioinformatics approaches were employed to identify the active ingredients and potential targets of cannabis for treating EP. Furthermore, network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking were used to elucidate the mechanism of cannabis against EP. A total of 360 compounds were collected in this work. Among them, 226 active compounds and 116 predicted targets were obtained based on absorption, distribution, metabolism and excretion (ADME) screening and databases, respectively. Among the 226 active compounds, most were cannabinoids. The topological analysis showed that cannabinoid receptor 1, albumin and glycogen synthase kinase-3 beta (CNR1, ALB and GSK3B) were the key targets with intense interaction. The GO and KEGG enrichment analysis suggested cannabis might produce the antiepileptic effects by regulating many pathways, including calcium signalling pathway, MAPK signalling pathway, GABAergic synapse, etc. Additionally, cannabinol methyl ether (M54) might be the leading compound based on molecular docking. Consequently, this study holistically illuminates the active constituents and mechanism of cannabis based on network pharmacology, which contributes to searching for leading compounds and development of new drugs in the treatment of EP. Supplemental data for this article is available online at https://doi.org/10.1080/13102818.2021.1942208 .