Main constituents of polyphenol complex from seagrasses of the genus Zostera, their antidiabetic properties and mechanisms of action

Abstract

The present review analyzed the recent experimental studies of the alleviating activity of main constituents of the polyphenol complex from seagrasses of the genus Zostera, namely rosmarinic acid, luteolin and its sulfated derivatives, on carbohydrate and lipid metabolism disorders. A number of studies by our group and others, in which various experimental models of diabetes and hyperlipidemia were used, show a therapeutic action of the polyphenol complex and the abovementioned phenolic constituents, when applied separately and in combination. Based on the analysis of the results of these studies, the probable mechanisms of the therapeutic action of these compounds in diabetes and hyperlipidemia were proposed.

Keywords: diabetes; flavonoids; hyperlipidemia; luteolin; metabolic syndrome; rosmarinic acid.

Figure 1.

Chemical structures of main components of polyphenol complex from seagrasses of the genus Zostera. (A) rosmarinic acid, (B) luteolin and (C) 7,3′-disulfate luteolin.

Figure 2.

High-performance liquid chromatography/mass spectrometry spectrum of polyphenol complex. Retention times (min): 12.48, 7,3′-disulfate luteolin; 12.83, rosmarinic acid; 14.88, luteolin; 15.54, apigenin.

Figure 3.

Signaling pathways of inflammatory gene expression in type 2 diabetes and metabolic syndrome and the strategy to prevent these pathologies with RA, LT and its analogues. RA, rosmarinic acid; LT, luteolin; NF, nuclear factor; FFA, free fatty acids; PPAR, peroxisome proliferator-activated receptor; TLR, Toll-like receptor; JNK, c-Jun N-terminal kinase.

Figure 4.

Proposed mechanisms of the AA of RA, LT and DSL. RA, rosmarinic acid; LT, luteolin; DSL, 7,3′-disulfate luteolin; NSAID, non-steroidal anti-inflammatory agent; SAID, steroidal anti-inflammatory agent; PKC, protein kinase C; PTC, protein tyrosine kinase; MAPK, mitogen-activated protein kinase; iNOS, inducible nitric oxide synthase; COX, cyclooxygenase; LOX, lipoxygenase; TNF-α, tumor necrosis factor; IL, interleukin; PLA2, phospholipase A2; AA, arachidonic acid.

Figure 5.

Proposed mechanisms of the protective effects of luteolin and 7,3′-disulfate luteolin on the example of macrophage cells.

Figure 6.

Proposed ways of permeation of LT and DSL into blood vessel cells and their inhibitory effect on scavenger receptors of oxLDL. (A) Permeation of DSL through damaged endothelial cells into the intima, where macrophage cells are located. (B) Inhibitory effect of LT and DSL on permeation of oxLDL into macrophage cells. oxLDL, oxidized low-density lipoproteins; LT, luteolin; DSL, 7,3′-disulfate luteolin.