The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?
Abstract
1. Introduction
2. Basic Pectin Molecular Aspects
2.1. Pectin Molecular Weight
2.2. Monosaccharides, Backbone, and Side Chains
2.3. Esterification Degree
2.4. Rheological Properties
2.5. Food Source
3. Gal-3 Binding Sites and Pectin Interactions
4. Pectin and Gal-3 Controversies
5. Pectin as Dietary Fiber: Some of the Gal-3 Independent Beneficial Effects to Human Health
6. Should Gal-3 Inhibition Be the Main Biological Effect Expected from Pectin?
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Authors | Polysaccharide Residue | Analysis Method | Binding Evaluation |
---|---|---|---|
Wu et al., 2020 [33] | RG-I from citrus canning process water | Surface plasmon resonance | Smooth binding curve through SPR with decreased affinity with galactan side-chain removal |
Zhang et al., 2016 [34] | MCP, RG-I-4, and p-galactan | Gal-3 hemagglutination, bio-layer interferometry, and surface plasmon resonance | RG-I-4 demonstrated higher Gal-3 avidity in comparison to the other two polysaccharides, with a KD at sub-micromolar range (RG-I-4 and p-galactan), but no significant result when testing competitive assays with known S-face inhibitors such as lactose |
Gao et al., 2013 [40] | Ginseng RG-I-4 domain | Gal-3 hemagglutination and surface plasmon resonance | RG-I-4 inhibited G3H and was bound specifically to CRD with high affinity with Ara residue location in the RG-I, changing the activity detected at the G3H assay |
Gunning, Bongaerts, Morris et al., 2009 [51] | RG-I, PG, and galactans | Atomic force microscopy, fluorescence microscopy, nuclear magnetic resonance, and flow cytometry | Galactan binding to Gal-3 is lectin-saccharide highly specific, while RG-I has low specificity, and PG was not specific. The data suggest that the lesser “sterical crowding” of the galactans alongside its beta-1,4 linear chain could be the reason for the better performance observed |
Shi et al., 2017 [52] | Ginseng RG-I-3A domain | Bio-layer interferometry, Gal-3 hemagglutination | Binding kinetics of RG-I-3A showed a high binding affinity with a KD of 28 nM through and also presented notable G3H inhibition |
Zhang et al., 2017 [83] | MCP-derived RG-I and HG portions | Gal-3 hemagglutination, bio-layer interferometry, ELISA, and nuclear magnetic resonance | Gal-3 bound to both portions separately but with a much more notable avidity when a combination of them (RG + HG) is performed, suggesting that this interaction exposes more binding sites at the lectin |
Miller et al., 2015 [84] | Galactomannans (GM) and polymannan | Nuclear magnetic resonance | The primary binding surface of the GM’s located mainly at F-face beta-sheets (7,8 and 9) |
Zheng et al., 2020 [89] | MCP-derived HGs of varying molecular weights | Nuclear magnetic resonance heteronuclear single quantum coherence spectroscopy and crystallography | Higher molecular weight HGs demonstrated more perturbances at F-face resonances and involved more S-face beta-sheets at the binding footprint. A possible binding of Gal-3 to the non-terminal HG sites is suggested, and it is shown a different S-face binding pattern of HG’s compared to lactose |
Miller et al., 2019 [90] | Galactan oligosaccharides of varying chain lengths | Nuclear magnetic resonance heteronuclear single quantum coherence spectroscopy | Binding affinity at the terminal non-reducing end of the galactans in the CRD S-face (beta-sheets 4, 5, and 6 chemical shifts mostly) increases with the increase in chain length |
Zhao et al., 2017 [91] | Pumpkin RG-I-containing pectin | Surface plasmon resonance | Moderate binding affinity towards Gal-3 through SPR, with a fast association between protein and polysaccharide (KA) and slow dissociation (KD) |
Miller et al., 2017 [92] | Ginseng RG-I-4 domain | Nuclear magnetic resonance heteronuclear single quantum coherence spectroscopy | Epitopes from RG-I-4 bind to three different labeled Gal-3 sites, two at the CRD and another one at NT. At lower concentrations, the F-face site is more activated, turning to S-face at higher ones |
Authors | Treatment | Study Type | Treatment Target | Observed Experimental Effects |
---|---|---|---|---|
Pedrosa, Lopes and Fabi, 2020 [7] | Papaya pectin acid and neutral fractions | In vitro | HCT 116, HT-29, and HCT-116 Gal-3−/− | Gal-3-mediated agglutination inhibition, cell viability decrease in both WT and knockout cells (suggesting Gal-3 independent pathways) |
Chen et al., 2018 [10] | SCFAs | In vivo | Male apoE−/− mice | Stimulation of Lxrα mediated genes expression related to intestinal cholesterol uptake and excretion; improved blood lipid profiles and anti-atherosclerotic property |
Li, Zhang, and Yang 2018 [11] | CP | In vivo | Healthy male C57BL/6J mice | Pectin-supplemented high-fat diet mice had reduced lower liver damage, lipid accumulation, and total serum triglyceride |
Brouns et al., 2012 [12] | Different DM and MW apple and citrus pectin (CP) | Human intervention | Mildly hyper-cholesterolemic men and women | Higher DM apple and citrus pectin lowered between 7 and 10% low-density lipoprotein cholesterol (LDL-C) compared to control |
Liu et al., 2016 [13] | CP | In vivo | Male Sprague-Dawley rats with induced type 2 diabetes | Enhanced glucose tolerance, blood lipid levels, reduced insulin resistance, pAKT expression upregulation, and glycogen synthase kinase 3 β (GSK3β) downregulation |
Fotschki et al., 2014 [14] | Apple fiber (low pectin) | In vivo | Male Wistar rats | Disaccharidase activity reduction, higher SCFA production, reduced serum glucose concentration |
Prado et al., 2019 [32] | Chelate-soluble fraction of papaya pectin | In vitro | HCT 116 and HT-29 human colon cancer cells | Gal-3-mediated agglutination inhibition, similar to lactose control; pre-treatment with lactose suggests cell Gal-3 independent proliferation reduction for one of the fractions (3CSF) |
Wu et al., 2020 [33] | CP fragments | In vitro | MCF-7 human breast cancer and A549 human lung carcinoma | Significant binding affinities to Gal-3; dose-responsive cell proliferation inhibition in vitro, not necessarily related to Gal-3 |
Gao et al., 2013 [40] | MCP, ginseng pectin fractions, potato galactans, and RG-I | In vitro | HT-29 human colon cancer cell line | RG I-4 from ginseng strongly inhibited Gal-3 mediated hemagglutination; better inhibition of cell adhesion and homotypic cell aggregation than lactose |
Stegmayr et al., 2016 [50] | MCP | In vitro | JIMT-1 breast cancer cells | No Gal-3 inhibition was detected; however, MCP pre-incubation resulted in the accumulation of Gal-3 molecules around intracellular vesicles |
Prado et al., 2020 [73] | Papaya pectins from different ripening periods | In vitro | THP-1 human monocytic cell | Different TLR’s activation and inhibition depend on the ripening period |
Hu et al., 2020 [85] | Lemon pectin | In vitro | Human pancreatic beta-cell | Unspecific and unspecified reduction of deleterious effects of inflammatory cytokines with very low (5%) degree of esterification pectin at cell culture |
Xu et al., 2020 [86] | MCP | In vivo | Male Wistar rats | Down-regulation of Gal-3, TLR, and MyD88, decreased expression of IL-1β, IL-18, and TNF-α |
Maxwell et al., 2016 [99] | Sugar beet and CP | In vitro | HT-29 human colon cancer cell line | Cell proliferation control and induction of apoptosis |
Pynam and Dharmesh, 2019 [101] | Bael fruit pectin fragments | In vitro and in vivo | Healthy Swiss albino mice and B16F10 cell line | Microbiota protection, tyrosinase down-regulation, Gal-3 binding, downregulation of Gal-3 gene, IL10 and IL17 cytokines |
Fang et al., 2018 [103] | MCP | In vitro | Human urinary bladder cancer (UBC) cells | Gal-3 down-regulation and inactivation of Akt signaling pathway, a decrease in Cyclin B1, G2/M phase arrest, Caspase-3 activation |
Hossein et al., 2019 [104] | MCP | In vitro | SKOV-3 and SOC (serous ovarian cancer) cells | Synergistic effect of PTX and MCP increasing caspase-3 activity and decreasing cyclin D1 expression level |
Abu-Elsaad and Elkashef, 2016 [105] | MCP | In vivo | Adult male Sprague-Dawley rats | Decreased liver fibrosis and necroinflammation, a decrease in MDA, TIMP-1, Col1A1, and Gal-3, increase in Caspase-3, gluthatione, and superoxide dismutase expression |
Martinez-Martinez et al., 2016 [106] | MCP | In vivo | Adult male Wistar rats | Attenuation of renal fibrosis-related biomarkers, osteopontin, cytokine A2, albuminuria and TGF-β1 |
Calvier et al., 2015 [109] | MCP | In vivo | Adult male Wistar rats, C57BJ6 WT and Gal-3−/− mice | Reverted fibrosing markers and Gal-3 augmentation levels, similarly to spironolactone |
Li et al., 2018 [110] | MCP | In vitro and in vivo | HEK293 cells and C57BL/6 male mice | Amelioration of renal interstitial fibrosis, lower collagen I and fibronectin in the kidney, reduced IL-1β mRNA levels, lower Gal-3 expression |
Prud’homme et al., 2019 [111] | MCP | Cohort and in vivo | C57BL6/J and C57BL6/J Gal-3 KO male mice | Cardiac fibrosis induced by model prevented by MCP treatment, IL-1β level maintained, protected, treated mice against renal inflammation |
Ibarrola et al., 2019 [112] | MCP | In vivo | Male Wistar rats | BNP serum level normalization, lower Gal-3 cardiac expression, reticulocalbin-3 and fumarase in the myocardium, IL-1β and CRP in serum |
Li et al., 2019 [113] | MCP and perindopril | In vivo | New Zealand male rabbits | Gal-3, collagen I, and III downregulation |
Vergaro et al., 2016 [114] | MCP | In vivo | Transgenic mice with aldosterone synthase gene overexpression | Reduced cardiac hypertrophy, fibrosis, Coll-1, and Coll-3 genes expression and also enhanced anti-inflammatory and anti-fibrotic effects when synergistically acting with Canrenoate |
Ibarrola et al., 2017 [115] | MCP | In vivo | Male Wistar rats | Gal-3, mRNA expression normalized, collagen I, fibronectin, α-SMA, TGF-β1, and CTGF mRNA expression reduced compared to pressure overload group, vascular inflammatory markers expression was also controlled |
Xue et al., 2019 [116] | Ginseng pectin fractions | In vitro and In vivo | Jurkat (human leukemia cells) and male IRC mice | MCP inhibited IL-2 expression, and the three pectin fractions utilized reversed cleaved caspase-3 formation alongside lactose. MCP and ginseng pectins inhibited ROS production in vitro. Reduced tumor weight and increased IL-2 secretion in vivo |
Lau et al., 2021 [117] | MCP | Interventional trial | Participants with high Gal-3 levels and hypertension | MCP had no impact regarding attenuating of cardiac-related risk factors |
Busato et al., 2020 [122] | Broccoli stalks pectin | In vitro and in vivo | Female albino swiss mice and peritoneal exsudate cells | Macrophage activation and higher phagocytic activity; IL-10 presence was higher at peritoneal fluid in vivo, but not at in vitro model |
Liu et al., 2008 [125] | MCP | In vitro and in vivo | CT-26 cells and Balb/c female mice | MCP did not alter Gal-3 expression at metastatic liver cells, although it did inhibit tumor growth and metastatic rate |
Courts, 2013 [126] | MCP | In vitro | Caco-2 monolayer | MCP fragments were absorbed through paracellular and to a lower degree by transcellular transports at in vitro culture |
Huang et al., 2012 [127] | Enzyme-treated CP | In vitro and In vivo | HepG2, A549, Colo 205, and HEK293 cells, BALB/c mice | Altered membrane permeability (LDH release) in the cancer cell lines; low weight oligogalacturonide was absorbed by the mice and the tumor cells, enhancing Gal-3 release to the medium |
Fan et al., 2018 [129] | Ginseng RG-I enriched pectins | In vitro | L-929 fibroblast cells | Modulation of cell migration and adhesion, independent of Gal-3 |
Nishikawa et al., 2018 [130] | Modified citrus pectin (MCP) | In vivo | Male C57BL/6 mice | Attenuated blood-brain barrier disruption Gal-3 upregulation, inactivation of ERK 1/2, STAT and MMP |
Sivaprakasam et al., 2016 [143] | 2% inulin, 2% pectin, and 1% cellulose | In vivo | Human colon cancer tissue and Ffar-2−/− C57BL/6J mice | Microbiota modulation, promotion of Bifidobacterium growth, and reduction of Prevotellaceae |
Kim et al., 2013 [144] | SCFAs | In vivo | WT, GPR41−/− and GPR43−/− mice | Activation of intestinal epithelial cells to produce chemokines and cytokines, GPR’s were essential in T effector cell activation and signaling pathways |
Tian et al., 2016 [146] | Sugar beet, soy, low DM, and high DM citrus pectin | In vivo | Male Wistar rats | More stimulation of Lactobacillus and Lachnospiraceae growth in sugar beet pectin, higher production of SCFA’s for low DM citrus and soy pectin |
Tian et al., 2017 [147] | Low DM and high DM citrus pectin | In vivo | Piglets | The slower fermentation process, alteration of main fermentation region, and higher Bacteroidetes predominance |
Ferreira-Lazarte et al., 2019 [148] | CP | In vitro | Dynamic gastric simulator with healthy volunteer fecal slurry donated | Growth stimulation of Bifidobacterium spp., Bacteroides spp., and Faecalobacterium prausnitzii, high increase in acetate and butyrate production |
Chen et al., 2013 [149] | Apple pectin oligosaccharides | In vitro | Fecal batch culture fermentation | Increased numbers of Lactobacillus and Bifidobacteria, a higher concentration of acetic, lactic, and propionic acid decreased number of Clostridia and Bacteroides |
Onumpai et al., 2011 [150] | Potato galactan, methylated citrus pectin, beet arabinan, Arabidopsis thaliana RG-I | In vitro | Fecal batch culture fermentation | Higher Bifidobacterium populations and higher SCFA’s yield increased Bacteroides-Prevotella groups |
Merheb, Abdel-Massih, and Karam, 2019 [153] | CP and MCP | In vivo | Female BALB/c mice | Upregulation of IL-17, IFN-γ, and TNF-α through IL-4 cytokine secretion in the spleen |
Amorim et al., 2016 [154] | Theobroma cacao pod husk modified pectin | In vivo | Female albino Swiss mice | Promotion of macrophage differentiation, nitric oxide production, and upregulation of IL-12, TNF-α, and IL-10 secretion |
Do Nascimento et al., 2017 [155] | Sweet pepper pectin | In vitro | THP-1 human monocytic cell | Modulation of TNF-α, IL-1β, and IL-10 production and secretion |
Popov et al., 2011 [156] | Sweet pepper pectin | In vivo | Male BALB/c mice | Higher IL-10 production with lower TNF-α release |
Ishisono et al., 2017 [157] | CP | In vivo | Male C57BL/6 mice | Suppression of IL-6 secretion from TLR activated macrophages and CD11c+ cells |
Vogt et al., 2016 [158] | Different DM lemon pectin | In vitro | T84 intestinal epithelial cells | NF-kB/AP-1 activation through TLR/MyD88 and protective effects in the intestinal barrier |
Wang et al., 2018 [159] | Hippophae rhamnoides L. berries pectin | In vivo | Cyclophosphamide induced immunosuppressive mice | Macrophage activation, MyD88 increased expression and upregulated expression of TLR4 |
Park et al., 2013 [160] | RG-II from P. ginseng | In vivo and In vitro | C57BL6 WT, TCR KO, TLR KO mice, and BMDC cells | Facilitation of CD8+ T cells, induced production of TNF-α, IL-12, IFN-γ, and IL-1β during dendritic cell maturation |
Sahasrabudhe et al., 2018 [161] | Lemon pectins with different DM | In vitro and In vivo | HEK-Blue WT and mutated cell lines, female C57BL/6 mice | Inhibition of TLR2-1 heterodimer, prevention of ileitis in the mice model |
Hu et al., 2021 [162] | Lemon pectins with different DM | In vivo | Sprague-Dawley male rats and C57BL/6 mice | Reduced peri-capsular fibrosis in vivo and decreased DAMP-induced TLR2 immune activation in vitro |
Kolatsi-Jannou et al., 2011 [163] | MCP | In vivo | Male C57BL/6J mice | Reduced Gal-3 expression, reduced renal cell proliferation, apoptosis, fibrosis, and proinflammatory cytokine expression |
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Pedrosa, L.d.F.; Raz, A.; Fabi, J.P. The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement? Biomolecules 2022, 12, 289. https://doi.org/10.3390/biom12020289
Pedrosa LdF, Raz A, Fabi JP. The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement? Biomolecules. 2022; 12(2):289. https://doi.org/10.3390/biom12020289
Chicago/Turabian StylePedrosa, Lucas de Freitas, Avraham Raz, and João Paulo Fabi. 2022. "The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?" Biomolecules 12, no. 2: 289. https://doi.org/10.3390/biom12020289
APA StylePedrosa, L. d. F., Raz, A., & Fabi, J. P. (2022). The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement? Biomolecules, 12(2), 289. https://doi.org/10.3390/biom12020289