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In this Review, we consider the pathophysiological relevance of specific galectin–glycan interactions from a translational perspective and discuss the design, mechanisms of action, selectivity and therapeutic relevance of galectin-targeted agents. We focus on the results of preclinical studies and clinical trials and highlight lessons learned from targeting galectins in a diverse group of disease states, including nonalcoholic steatohepatitis (NASH) 19, idiopathic pulmonary fibrosis (IPF) 22, 23, 24, as well as various malignancies 11, 17. These examples underscore the numerous potential opportunities to capitalize on galectin–glycan interactions for therapeutic purposes. This was actually a large dose, so the fact that it was tolerated well by children is encouraging. The dose of MCP used in this study was equivalent to one scoop of Pectasol-C modified citrus pectin three-times daily for three months. (In our practice, we treat adults with one scoop twice daily for between 45 and 90 days, which we have found effective at lowering serum lead levels.) Slowing Heart Disease To achieve higher selectivity towards GAL3, interactions between galectins and alternative monosaccharides, including d-mannose, d-talose and d-gulose derivatives have been evaluated, although these compounds exhibited no significant functional activity in in vitro or in vivo assays 177, 178, 179, 180, 181, 182. However, a recent study reported that GAL9C and GAL9N CRDs demonstrated good affinity towards synthetic 3-deoxy-3- N-arylated-α- d-galactoside ( 4) and α-guloside ( 5) derivatives, respectively, compared with other galectins, as determined by fluorescence anisotropy assays 183 (Fig. 3c). H. Dresler, et al., “Effect of PectaSol-C Modified Citrus Pectin (P-MCP) Treatment (tx) on PSA Dynamics in Non-Metastatic Biochemically Relapsed Prostate Cancer (BRPC) Patients (pts): Results of a Prospective Phase II Study,” Eur. Urol Suppl. 17(14): e2849 (2018).
PectaSol-C Modified Citrus Pectin, Potassium, Sodium, Dietary Fiber, Vegetable capsule (natural vegetable cellulose, water), stearic acid, magnesium stearate, microcrystalline cellulose, silicon dioxide.
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GI health: This MCP is also shown to offer functional prebiotic benefits as an oligosaccharide-rich fibre. One study with the USDA and Rutgers showed that as a prebiotic fibre, MCP reduced Shiga toxin cytotoxicity from the aggressive strain of E. coli 0157:H7, which has been implicated in recent food contamination outbreaks. 22 Formulating with MCP Other polysaccharides have also emerged as potential galectin inhibitors. For example, RN1 ( 20, Fig. 4), an arabinogalactan polysaccharide isolated from the flowers of the Chinese ginseng plant ( Panax notoginseng), was proposed as a GAL3 inhibitor. This compound showed antitumoural activity in pancreatic ductal adenocarcinoma both in vitro and in vivo 236. Other ginseng-derived pectins prevented GAL3-driven T cell apoptosis and reduced tumour growth in mouse models of sarcoma 237. Peptides and peptidomimetics
From driving proinflammatory, profibrotic and procancerous pathways to promoting immune evasion, metabolic dysfunction and blood-brain barrier permeability, Gal-3 plays such a fundamental role that some experts are calling for a new category of health conditions: Elevated Galectin-3 Diseases. G. Hossein, et al., “Synergistic Effects of PectaSol-C Modified Citrus Pectin an Inhibitor of Galectin-3 and Paclitaxel on Apoptosis of Human SKOV-3 Ovarian Cancer Cells,” Asian Pac. J. Cancer Prev. 14(12), 7561–7568 (2013). This natural product is derived from the pith of citrus fruit peels, including lemons, limes, oranges and grapefruits, and is modified using a proprietary enzymatic and pH process. This unique modification process ensures that PectaSol-C MCP has the correct molecular weight necessary to promote optimal cellular wellness of the chest, male organ, lungs and more.There were also no negative side effects observed in a clinical trial involving children with lead toxicity in China. For three months, the hospitalized children between the ages of 5 and 12 were given 15 g of MCP in three divided doses a day [ 4]. J. Jiang, I. Eliaz and D. Sliva, “Synergistic and Additive Effects of Modified Citrus Pectin with Two Polybotanical Compounds in the Suppression of Invasive Behavior of Human Breast and Prostate Cancer Cells,” Integr. Cancer Ther. 12(2), 145–152 (2013).
C. Ramachandran, et al., “Activation of Human T-Helper/Inducer Cell, T-Cytotoxic Cell, B-Cell, and Natural Killer (NK)-Cells and Induction of Natural Killer Cell Activity Against K562 Chronic Myeloid Leukemia Cells with Modified Citrus Pectin,” BMC Complement Altern. Med. 11, 59 (2011). Plant-derived polysaccharides have also been proposed as therapeutics for liver, kidney and lung fibrosis, mainly via mechanisms that involve inhibition of GAL3 (refs. 142, 146). Inhibition of GAL3 with belapectin ( 18, Fig. 4) and Davanat ( 19, Fig. 4) was first evaluated in a toxin-induced model of liver fibrosis 232. Intraperitoneal administration of these polysaccharides resulted in decreased collagen content, attenuated liver fibrosis, diminished cirrhosis and a reduced percentage of GAL3-expressing macrophages 232. These two inhibitors were also tested in a murine model of NASH 233. Intravenous administration of belapectin resulted in a substantial reduction in collagen deposition, hepatocellular damage, NASH activity and fibrosis — features that were associated with reduced markers of inflammation that included inducible nitric oxide synthase (iNOS) and CD36 + pro-inflammatory macrophages. By contrast, administration of Davanat had no effect 233. A phase I clinical trial of belapectin ( 18) in patients with NASH with advanced hepatic fibrosis revealed no toxicity and good tolerability 234 (NCT01899859, Table 1). Two phase II clinical trials evaluated the efficacy of this compound in liver fibrosis. In patients with NASH with advanced fibrosis (NCT02421094, Table 1), belapectin had no significant effects on levels of non-invasive biomarkers of liver inflammation or fibrosis over a 4-month period 234. In liver fibrosis and resultant portal hypertension in patients with NASH cirrhosis 235 (NCT02462967, Table 1), belapectin had no impact on fibrosis or nonalcoholic fatty liver disease activity score. However, in a patient subgroup it showed a significant effect on portal pressure and prevented the development of oesophageal varices, which is an early sign of serious complications in patients with cirrhosis. This led to the development of a phase IIb/III trial designed to evaluate its safety and efficacy specifically in patients with NASH-associated cirrhosis for the prevention of oesophageal varices (NCT04365868, Table 1). But there are some differences between these natural pectins and the MCP variety. Our intestines can’t absorb pectin directly from fruits. But the modified version has shorter carbohydrate chains and a lower molecular weight [ 1], allowing it to be absorbed into the bloodstream where it can then potentially exert benefits. Benefits of Modified Citrus Pectin One randomized clinical trial with 125 participants who had mild to moderate high LDL (low-density lipoprotein) cholesterol found that use of guar gum plus pectin helped to normalize cholesterol levels. Lau ES, Liu E, Paniagua SM, Sarma AA, Zampierollo G, López B, et al. Galectin-3 Inhibition With Modified Citrus Pectin in Hypertension. JACC Basic Transl Sci. 2021 Jan 6;6(1):12–21. DOI: 10.1016/j.jacbts.2020.10.006. PMID: 33532663. PMCID: PMC7838053.Natural pectin is something that we’re all familiar with, even if we don’t know what it’s called. This is the spongy pulp found in the peels of citrus fruits such as oranges, limes, lemons, and grapefruit, as well as in apples and plums.
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