https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154165/
Untitled Document
Plants contain numerous glycoconjugates that are metabolized by specific glucosyltransferases and hydrolyzed by specific glycosidases, some also catalyzing synthetic transglycosylation reactions.
The documented value of plant-derived glycoconjugates to beneficially modulate metabolism is first addressed. Next, focus is given to glycosidases, the central theme of the review.
The therapeutic value of plant glycosidases is discussed as well as the present production in plant platforms of therapeutic human glycosidases used in enzyme replacement therapies.
The increasing knowledge on glycosidases, including structure and catalytic mechanism, is described. The novel insights have allowed the design of functionalized highly specific suicide inhibitors of glycosidases. These so-called activity-based probes allow unprecedented visualization of glycosidases cross-species. Here, special attention is paid on the use of such probes in plant science that promote the discovery of novel enzymes and the identification of potential therapeutic inhibitors and chaperones.
Balanced consumption of vegetables is nowadays in the center of attention, particularly prompted by the worldwide epidemic of obesity and associated health problems. There is considerable interest in plant products from practitioners of regular medicine and pharmaceutical industry. Of note, the first generation of pharmaceuticals largely consisted of plant-derived products or minor chemical modifications thereof. The longstanding popularity of natural plant products with alternative medicine advocates stems in many cases from ancient use of such materials in traditional medicine.
The chemical structure of plant glycosides determines their biological action(s) and bioavailability (uptake). In this respect, attention is first paid to glycosylated flavonoids.
Glycosylated Flavonoids
The predominant polyphenols in food (i.e., fruits, vegetables, nuts) and beverages (i.e., tea, wine) are flavonoids. Plant flavonoids can be categorized into subclasses: flavonols, isoflavonols, flavones, flavanones, flavanols (catechins), and anthocyanidins. Daily consumption of several milligrams of flavonoids (25 mg to 1 g/day) is common.
Many plant flavonoids are glycosylated. Glycosides are linked to the phenolic hydroxyls, via α- or β-d-glycosidic linkages. This type of modification may involve a single oligosaccharide or in some cases a polysaccharide moiety. Commonly reported benefits of flavonoid glycosides are anti-oxidants and anti-inflammatory activities which find application in prevention and disease management
The anti-inflammatory effects of flavonoids can be attributed to reduction of cytokine-induced inflammation by the inhibition of tumor necrosis factor-α (TNF-α) signaling and reduced expression of pro-inflammatory genes by down-regulation of NF-κB. An example is provided by the anti-inflammatory flavonol kaempferol which is present in broccoli, tea and vegetables. During osteoporosis, pro-inflammatory cytokines, e.g., TNF-α, are expressed and cause bone disruption and further cytokine production. Kaempferol antagonizes the TNF-α induced production of interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP1a), as well as the RANKL triggered osteoclast precursor cell differentiation. Another example is the anti-inflammatory effect of glycosylated anthocyanins present in blueberries, malvidin-3-O-glucoside and malvidin-3-O-β-d-galactoside. These molecules reduce the levels of MCP1, intercellular adhesion and vascular cell adhesion molecule-1 at protein and mRNA level in endothelial cells through the inhibition of TNF-α. In addition, they block the NF-κB pathway by affecting IκBα degradation and the nuclear translocation of p65.
For many flavonoids miscellaneous anti-cancer effects have been reported. The presumed modes of action of flavonoids as anti-cancer agents are diverse and the role of glycosylation in such anti-tumor effect is often not well understood. Examples of flavonoids with reported anti-tumor action are kaempferol, peonidin 3-O-β-d-glucoside, genistein, genistin, and EGCG. Genistein and genistin are, however, also reported to stimulate breast cancer cells in vivo at very low concentrations (nM range), acting as estrogen agonists in mice mammary glands. Daidzin of soybeans is another well-studied isoflavone 7-O-β-d-glucoside with similar anti-cancer properties as genistein. Anti-cancer action has also been documented during the last decades for apigenin, hesperidin and its aglycone hesperetin.
