Phlorotannins: From isolation and structural characterization, to the evaluation of their antidiabetic and anticancer potential

Abstract

Glossary of Abbreviations iNOS: inducible nitric oxide synthase COX-2: cyclooxygenase 2 CAT: catalase SOD: superoxide dismutase GSH-px: glutathione peroxidase Bcl-2: -cell lymphoma 2 (anti-apoptotic protein of the Bcl-2 family) GLUT-4: glucose transporter type Fas: cell surface death receptor XIAP: X-linked inhibitor of apoptosis protein FLIP: FLICE (caspase 8)-inhibitory protein AKT: serine/threonine-specific protein kinase, also known as PKB (protein kinase B) Bid: BH3 interacting domain death agonist (pro-apoptotic protein of the Bcl-2 family) Bim: BH3 only protein (pro-apoptotic member of the Bcl-2 family) Bak: Bcl-2 homologous antagonist/killer (pro-apoptotic protein of the Bcl-2 family) Bax: Bcl-2-associated X protein (pro-apoptotic member of the Bcl-2 family) p53: tumor suppressor protein (p) 53 NF-B: nuclear factor kappa B, a transcription factor involved in stress responses and regulation of cell proliferation and apoptosis Bcl-xl: -cell lymphoma-extra large (anti-apoptotic protein of the Bcl-2 family) PI3K: phosphatidylinositol 3-kinase RAF-1: rapidly accelerated fibrosarcoma, a serine/threonine-specific kinase ERK: extracellular signal-regulated kinase EGFR: epidermal growth factor receptor, a proliferation-stimulating protein Con formato: Español (Chile) Con formato: Inglés (Estados Unidos) Con formato: Inglés (Reino Unido) According to Liu (2004), phytochemicals are categorized into six major groups: phenolic compounds, alkaloids, nitrogen-containing compounds, organosulfur compounds, phytosterols and carotenoids. According to Liu (2004), phytochemicals are bioactive non-nutritive compounds present in fruit, vegetables and other plant foods that have been related to reductions in the risks of major NCDs. They have been widely studied in the last two decades through in vitro assays, in vivo models and clinical trials, which have shed light into the structure-function relation responsible for their healthpromoting effects. In plants, phytochemicals accomplish defence and reproductive functions (Huang, Xiao, Burton-Freeman, & Edirisinghe, 2016). They are categorized into six major groups: phenolic compounds, alkaloids, nitrogen-containing compounds, organosulfur compounds, phytosterols and carotenoids. Phenolic compounds are the most studied phytochemicals since they are ubiquitous and abundant in all plant-based diets (Tsao, 2010). They are chemically defined as compounds having one or more aromatic rings with one or more hydroxyl groups (Liu, 2004). One high-value group of polyphenolic compounds-or polyphenols-only found in brown seaweeds are phlorotannins. These have attracted considerable interest because of their superior antioxidant capacity (Shibata, Ishimaru, Kawaguchi, Yoshikawa, & Hama, 2008; Wang et al., 2012) and valuable biological activities, such as anti-inflammatory, antihyperglycaemic and anti-tumour (Catarino, Silva, & Cardoso, 2017). Although phlorotannins have been widely studied through in vitro assays, in vivo models and some clinical trials, which have shed light into a possibl...

Extraction, Enrichment, and LC-MSn-Based Characterization of Phlorotannins and Related Phenolics from the Brown Seaweed, Ascophyllum nodosum

“…However, the level of complexity for the major phlorotannin component (m/z [M − 2H] 2− = 1117; apparent MW 2234; possible fucaphlorethol of DP 18) highlighted in this paper illustrates the daunting extent of data interpretation required to make inferences of overall structure. Also, MS-based analyses are inherently limited by their mass range and cannot deal with the high molecular weight phlorotannin species known to be present in brown seaweeds [2,15]. However, the molecular range could be extended by using other MS systems with higher MW ranges such as MALDI-TOF, as described previously e.g., [32].…”

“…Overall, the MS 2 evidence ( Table 2) strongly suggested that the phlorotannin oligomers were fucophlorethols as they contained aryl ether linkages [2]. Due to the three-way symmetry of the phloroglucinol molecule, -C-C-phenyl linkages are always effectively meta-orientated [15]. However, PG units attached through aryl ether bridges can occur at hydroxyls at ortho, meta or para positions on the rings so the possibilities for different isomeric structures are large especially as the DP increases.…”

“…The phlorotannin series outlined above is based on a phlorethol structure, oligomers of phloroglucinol attached through aryl ether (-C-O-C) bonds but the addition of phloroglucinol units (124 amu) to achieve this series could also be achieved through phenyl (-C-C-) linkages (see Figure 3). In fact, this series of m/z values could arise from phloroglucinol units linked by all phenyl linkages (called fucols), all aryl ether linkages (called phlorethols) or a mixture of both (called fucophlorethols) [2,15] It was notable that these "phlorotannin" MS signals were approximately 4-fold enriched in the bound fraction obtained after SPE (see FSD in Figure 1B). Also, the bound acetone fractions from the Sephadex LH-20 separation also showed this enrichment in UV-absorbing peaks between 12 and 21 min ( Figure 4A).…”

“…For example, extending from a diphorethol structure to a triphlorethol structure can produce structurally discernible triphlorethol A and B isomers [2] depending on the positioning of the "new" aryl ether bond. Also, branching can also occur within fucol type phlorotannins composed of only phenyl linkages if one of the PG units has 3 rather than 2 linkages to other PGs [2,15]. Indeed, other studies have reported multiple apparent isomers of phlorotannin oligomers from Ascophyllum [28,29,31] and other brown seaweeds [37].…”

“…The phlorotannins have considerable antioxidant activity e.g., [13][14][15] and have been mooted as food-grade additives to prevent spoilage [16]. They have also been associated with specific health beneficial effects in related to disease states such as inflammation [17], cancers [18], diabetes [19] and hyperlipidemia associated with cardiovascular issues [20], which may be independent of their antioxidant activity.…”