Investigation of the Potential Phlorotannins and Mechanism of Six Brown Algae in Treating Type II Diabetes Mellitus Based on Biological Activity, UPLC-QE-MS/MS, and Network Pharmacology

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.