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Galactomannans are naturally occurring biocompatible and biodegradable nonionic polysaccharides comprised of mannose and galactose residues. They are under investigation for the design of various drug delivery carriers such as matrix tablets, microparticles, nanoparticles/nanocomposites, polymeric micelles, hydrogels, as well as pharmaceutical excipients. Amongst galactomannans, guar gum, locust bean gum, and fenugreek gum are the biomaterials mostly investigated for their potential utility as nanocarriers for various purposes, either in their native or modified forms. The galactomannan-based nanomaterials have been fabricated by adopting various strategies. These galactomannan nanomaterials have been tested for oral vaccination, oral insulin delivery, cancer cell & macrophage targeting, controlled drug delivery, heavy metal extraction and wound dressing applications. The galactomannan has attracted the attention of researchers as reducing agents for the green synthesis of metal nanoparticles as well. These nanometals have shown improved antimicrobial, antioxidant and anticancer activities. In vitro toxicity of the nanomaterials is also assessed in some instances. Others such as cassia gum, tara gum, Delonix, Leucaena leucocephala, Punica granatum galactomannans are amongst the least studied materials for biological applications. This review describes various strategies adopted for the synthesis of galactomannan-based nanomaterials, their properties and applications, especially in the field of drug delivery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The search for lipid-lowering drugs is important for clinical medicine. This review summarizes our research findings regarding the hypolipidemic activity of polysaccharides. There are several validated agents altering lipid levels which reduce the risk of atherosclerotic cardiovascular events. Nonetheless, for many people, the risk of such an event remains unacceptably high despite treatment with these agents. This situation has prompted the search for new therapies to reduce the residual cardiovascular risk. The lipid-lowering effect of β-glucans consumed with food was demonstrated in patients with atherosclerosis. The mechanism of the protective effect of β-glucans is poorly studied. The effects of β-glucans are mediated by Toll-like receptors, by dectin-1, and possibly by other receptors. Nevertheless, the mechanism of the protective action of β-glucan in lipemic mice has been studied insufficiently. This review will present up-to-date information regarding experimental hypolipidemic polysaccharide compounds that hold promise for medicine. Phagocyte-specific chitotriosidase in humans contributes to innate immune responses against chitin-containing fungi. This enzyme has been first described in patients with Gaucher disease and serves as an important diagnostic biomarker. It has been reported that, in mice, chitin particles of certain size are recognized by macrophages through Toll-like receptors, dectin-1, and to a lesser extent through mannose receptor.

Objective: Certain plant polysaccharides may provide psychological health benefits. The aim of this study was to evaluate whether they can acutely improve mood and cognitive function., Method: In a randomized, double-blind, placebo-controlled, between subjects design trial, 73 middle-aged adults consumed 4 g of a proprietary mixture of non-starch polysaccharides (NSPs) (Ambrotose® complex), a rice flour placebo, or a sucrose control. Participants completed testing at baseline and 30 minutes post-consumption. Acute effects of consumption on mood, cognition, and blood glucose were evaluated during mental tests designed to induce mental fatigue., Results: Significant improvement in recognition and working memory performance was observed in the group that consumed NSP compared with placebo or sucrose. Improvements in memory performance following NSP intake were independent of changes in blood glucose., Discussion: This is the first report of acute behavioural improvement following plant polysaccharide intake in healthy middle-aged adults under conditions of mental fatigue. The findings suggest that certain NSP may enhance memory performance through mechanisms other than elevated blood glucose.

Objectives: To determine the efficacy and the immunomodulatory function of Z-100 alone or combined with meglumine antimoniate on Leishmania amazonensis infection., Methods: The effect of the compounds was evaluated by microscopic counting of intracellular amastigotes in macrophages stained with Giemsa, or axenic promastigotes, and IC(50) was determined by linear regression. The antileishmanial effect of the compounds was assessed in infected BALB/c mice by a limiting dilution analysis and the production of gamma interferon (IFN-gamma), interleukin 10 (IL-10), IL-4, IgG1 and IgG2a was measured by ELISA., Results: In vitro, Z-100 showed antileishmanial activity against intracellular amastigotes of L. amazonensis with an IC(50) of 13 mg/L. Moreover, infected macrophages treated with Z-100 (12 mg/L) showed smaller parasitophorous vacuoles with fewer parasites than the control. In addition, the efficacy of Z-100 plus meglumine antimoniate [14 mg/L pentavalent antimony (Sb(v))] was higher (46% inhibition) than either Z-100 or meglumine antimoniate alone. Nevertheless, no effect of Z-100 on axenic promastigotes was observed. Infected BALB/c mice treated with Z-100 (100 microg/kg) alone did not show any antileishmanial effects in comparison with the control group, and IFN-gamma, as well as IL-10 and IL-4, was up-regulated by the treatment. In addition, both IgG1 and IgG2a were also increased by the Z-100 treatment. Although Z-100 plus meglumine antimoniate (14 or 28 mg/kg Sb(v)) controlled both the parasite load and the footpad swelling in comparison with control mice, no significant differences were found with meglumine antimoniate alone., Conclusions: In vitro, Z-100 alone or combined with meglumine antimoniate showed an antileishmanial effect on L. amazonensis. However, no effect was observed in infected BALB/c mice treated with Z-100, suggesting that the up-regulation of IL-10 and IL-4 production by the treatment could be interfering with the development of a protective Th1-type response. For further understanding of the effects of Z-100 in vivo, another strain of mice such as C57BL/6 should be tested in future.

Tamm-Horsfall glycoprotein (THGP), produced exclusively by renal cells from the thick ascending limb of Henle's loop, is attached by a glycosyl-phosphatidylinositol (GPI)-anchor to the luminal face of the cells. Urinary excretion of THGP (50-100 mg/day) occurs upon proteolytic cleavage of the large ectodomain of the GPI-anchored form. N-Glycans, consisting of a large repertoire of sialylated polyantennary chains and high-mannose structures, account for approximately 30% of the weight of human urinary THGP. We describe: (i) the involvement of urinary THGP high-mannose glycans in defense against infections of the urinary tract, caused by type-1 fimbriated Escherichia coli, which recognize high-mannose structures, (ii) the role of GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4GlcNAcbeta1-3Gal (Sd(a) determinant) carried by human THGP in protecting the distal nephron from colonization of type-S fimbriated E. coli which recognise NeuAcalpha2-3Gal, (iii) the inhibitory effect of sialylated THGP on crystal aggregation of calcium oxalate and calcium phosphate, thus preventing nephrolithiasis. Finally, we outline the importance of N-glycans in promoting the polymerization of THGP, a process resulting in the formation of homopolymers with an M(r) of several million in urine. Since THGP defense against diseases of the urinary tract mainly consists in binding damaging agents, its ability to behave as a multivalent ligand significantly enhances this protective role.

Lichens have been used for medicinal purposes throughout the ages, and beneficial claims have to some extent been correlated with their polysaccharide content. Of 13,500 lichen species growing worldwide, less than 100 species have been investigated for polysaccharide content. Lichen polysaccharides are mainly of three different structural types: beta-glucans, alpha-glucans, and galactomannans. In addition, a few complex heteroglycans have recently been described, such as thamnolan, a water-soluble, immunologically active heteroglycan with a novel rhamnopyranosylgalactofuranan type of structure. A number of investigations have been carried out on biological effects of lichen polysaccharides, most notably antitumour, immunomodulating, antiviral, and memory-enhancing effects. The current review summarizes present knowledge on the structural characteristics and biological activity of lichen polysaccrides.

The effect of different polysaccharides fermented in the large intestine and liable to lower plasma cholesterol was investigated in rats. Male rats were assigned to one of five treatment groups: control diet or a diet containing pectin, guar gum, gum arabic or beta-cyclodextrin. The four compounds were effectively fermented, yielding cecal short-chain fatty acids (SCFA) concentrations in the range of 130 to 170 mmol/L. Relative to controls, the cecal concentration of propionate was significantly higher in rats fed all fibers, especially those fed guar gum (+190%) or beta-cyclodextrin (+385%). All the fermented carbohydrates elicited a significant cholesterol-lowering effect, which was most potent in rats fed guar gum or beta-cyclodextrin, the two fibers that also significantly depressed plasma triglycerides. These two carbohydrates significantly lowered LDL and HDL1 cholesterol, triglyceride-rich lipoprotein triglycerides and apolipoprotein E levels. Apolipoprotein B was lowered only by beta-cyclodextrin. The microsomal activities of hydroxymethylglutaryl (HMG) CoA reductase and of cholesterol 7 alpha-hydroxylase were markedly elevated in rats fed guar gum or beta-cyclodextrin and, to a lesser extent, in those fed pectin compared with controls. Increased bile acid excretion seems to be essential in the cholesterol-lowering effect of soluble fibers and related compounds. This effect is connected to induction of HMG CoA reductase and lowering concentrations of apolipoprotein E-containing particles.

The effect of guar (15.6 g/day), a dietary fibre, and simultaneous administration of bezafibrate (600 mg/day) during dietetic treatment on the plasma lipoproteins and apolipoproteins was investigated in 12 patients with familial hypercholesterolemia (corresponding to the HLP type IIa pattern). Either bezafibrate alone or bezafibrate in combination with guar was administered in a cross-over study for 3 months. Guar led to an additional lowering of the total cholesterol in the plasma by 7% (P less than or equal to 0.05) associated with a fall of the low density lipoprotein cholesterol (LDL-cholesterol (LDL-cholesterol) by 13% (P less than or equal to 0.01) without any changes in the very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterols. In parallel with the decrease in LDL-cholesterol, the apoprotein B also was diminished by 20% (P less than or equal to 0.05). The plasma triglyceride level and the triglyceride distribution within the individual lipoprotein fractions were not altered in any consistent manner by the addition of guar. Neither the fasting plasma glucose level nor the body weight were affected. The side-effects due to guar treatment consisted of slight nausea, meteorism and constipation, but this did not in any of the cases lead to early termination of the study. These results demonstrate that guar exerts its cholesterol-lowering effect in addition to that of bezafibrate.

A synthetic stearolymannan phosphate designated as SMP-Fr. I-d, consisting of three components, fatty acid, polysaccharide, and phosphate, enhanced the therapeutic effect of Mitomycin-C in mice implanted with 1 x 10(7) cells of Ehrlich carcinoma ascites form. Namely, 50% of the mice survived more than 60 days when ineffective doses of 0.5 mg/kg of Mitomycin-C and 50 mg/kg of SMP-Fr. I-d were administered intraperitoneally once daily for 7 days. SMP-Fr. I-d was found to be virtually non-toxic even in a dose of 1,000 mg/kg intraperitoneally in mice.

When nine diabetic patients supplemented either their normal home diets (four patients) or metabolic ward diets (five patients) with 25 g guar gum daily for 5 or 7 days their mean urinary glucose excretion fell by 46% (P less than 0-05) and 54% (P less than 0-01), respectively. Gel-forming,, unabsorbable carbohydrate may therefore be a useful adjunct to anti-diabetic therapy, irrespective of the type of treatment or insulin dosage used.

The D-mannan of Saccharomyces cerevisiae X2180-1A-5 mutant strain, which possesses a main chain composed of alpha-(1 yields 6) linked D-mannopyranosyl residues and a small proportion of branches composed of alpha-(1 yields 2)- and alpha-(1 yields 3)-linked D-mannopyranosyl residues, showed strong growth-inhibitory activity against mouse-implanted Sarcoma 180 and Ehrlich-carcinoma solid tumor. The observation that the level of this activity was nearly identical with that of the D-mannan of a wild-type strain of bakers' yeast, which possesses a high proportion of branches composed of alpha-(1 yields 2)-and alpha-(1 yields 3)-linked D-mannopyranosyl residues, suggests that the branches are not essential for antitumor activity. The partial acid-degradation products of both D-mannans, the molecular weight of which was one-third of that of each parent D-mannan, had only one half of the antitumor activity of the parent D-mannans. This suggests that molecular size is the most important factor for the differences in acitvity of the polysaccharides of wild and mutant strains.

The effects of dietary supplementation with granulated guar gum (21 g/day in three divided doses at the main meals), were compared with placebo response during three months in a double-blind, cross-over trial in 11 Type 2 (insulin-independent) diabetes. The nine patients who complete the study (two dropped out because of side-effects) showed a significant reduction in both basal and post-prandial hyperglycaemia as well as of urinary excretion of glucose during guar gum supplementation. No change in mean bodyweight was observed during the study. Mean fasting and post-prandial plasma insulin levels were similar during both study periods, but the two subjects who received no oral hypoglycaemic agents had lower insulin levels during the guar gum period. Mean serum total- and LDL-cholesterol concentrations were significantly lower during the guar gum period, whereas the HDL-cholesterol level remained unchanged. Long-term administration of guar gum induced a sustained improvement in diabetic control in Type 2 diabetes.

The Authors have studied an experimental product (L. G. 140/S), based on GUAR GUM, to establish its effectiveness and tolerability as a dietetic support in the treatment of obesity. The clinical research work has been conducted on 21 obese subjects (18 females and 3 males) aged 17 to 58 and treated with a hypocaloric and hypoglycemic diet. This preparation has proved useful in helping the patients to conform to the dietary restrictions and/or in normalizing their intestinal transit. No objective or subjective symptoms certainly referable to this preparation have been observed. The administration of the product has been interrupted for precautionary reasons in some cases, since it was not indispensable. Considering the good results they have obtained in terms of tolerability and agreeableness of this product, the Authors conclude that it can be considered a useful support to the restrictive dietary regimen, which is still considered - together with physical activity - the only sound and effective remedy in the treatment of obesity.

Nineteen patients with primary hypercholesterolaemia previously stabilized on diet alone were treated with a new formulation of guar gum (6g t.d.s. with meals) in a placebo-controlled, single-blind study. Seventeen patients completed 3 months treatment without serious side effects, while 2 patients withdrew immediately because of severe diarrhoea. Thirteen patients have completed 12 months treatment with guar gum. There have been no significant changes in safety parameters. Plasma cholesterol was reduced by a significant 15% during the first 3 months of treatment (7.9 +/- 0.8 vs 6.7 +/- 1.0 mmol/l, P less than 0.001) and this effect has been sustained for 12 months. The fall in plasma cholesterol was associated with a significant 20% fall in LDL cholesterol, but with no change in HDL cholesterol. Plasma triglycerides did not change significantly. Percentage cholesterol absorption was reduced by guar gum in 4/5 normal subjects examined.

In a double-blind crossover study the effect of ingested guar gum granules, 15 g/d for 3 months, on blood lipids was evaluated in twelve obese hypercholesterolaemic patients. Serum total cholesterol decreased during the guar gum period in eight of the ten patients who completed the study. The mean serum cholesterol was 8.5 +/- 0.4 mmol/l after the guar gum period as compared to 8.9 +/- 0.3 mmol/l after the placebo period. The mean HDL-cholesterol or body weight showed no significant changes during either treatment period. Guar gum administration did not cause any significant changes in 24-h urinary excretion of sodium, potassium, calcium or magnesium. It is concluded that the administration of guar gum granules seems to reduce serum total cholesterol in hypercholesterolaemic patients without exerting an effect on HDL-cholesterol. The beneficial effect of guar gum is independent of the changes in body weight.

The diet of 10 insulin-dependent diabetics was modified for 3 months by the addition of guar gum to buttermilk rusks. Control of glycaemia was assessed by serial determination of total glycosylated haemoglobin A1. The effect of guar on serum cholesterol levels was noted. Guar gum supplementation failed to improve the long-term diabetic control, but significantly reduced serum cholesterol levels (P less than 0,01). The effect of guar on lipoprotein levels should be investigated more fully.

Guar gum, a storage polysaccharide galactomannan and a form of dietary fiber, was administered to 10 patients with type II a or b hyperlipidemia for 2 weeks. Five grams of gum was given before each of three meals daily, either in a specially prepared soup or mixed with fruit juice or milk. No other deliberate change of diet was made. Three patients had been taking 12 to 16 g/day of cholestyramine for more than 2 years and one had been taking 1000 mg of clofibrate daily. These drugs were continued throughout the trial. Serum cholesterol levels of all 10 patients had been stable for 6 to 18 months before the trial at the start of which the mean level was 345 +/- 15 mg/dl. After 2 weeks of guar gum the mean was 308 +/- 16 mg/dl, a fall of 10.6% (P less than 0.01). Serum triglyceride was not changed significantly. Guar gum, which can be incorporated into foods, merits further study as a potential hypocholesterolemic agent.

Guar gum at different concentrations was incorporated into foods from six groups to establish some principles to aid the production of high-viscosity therapeutic foods. The amounts of gum that could be incorporated into a food, without major loss of acceptability, were higher in products with low final water content than those with high final water content. The domestic preparation of these recipes should be possible provided that recipe modifications are carefully followed.

The effect of guar gum in lowering urinary glucose excretion and plasma cholesterol was studied in ten sulphonylurea-treated non-insulin dependent diabetic patients during a four week treatment period. The 24-hour urinary glucose excretion fell gradually and increased again to pretreatment value after withdrawal of guar. The glucose output dropped by 33 and 51% in the 3rd and 4th week of the guar treatment period (p less than 0.01) compared to the mean of the pre-plus postguar level. The plasma cholesterol concentration also fell significantly during treatment with guar (p less than 0.01).

The effect of guar gum preparation on the glycemic control of 12 pregnant insulin-dependent diabetic patients was investigated. The study was performed on inpatients and lasted 3 wk (from week 32 of pregnancy and onward). Weeks 32 and 34 were control periods during which time the patients had their normal diet only. During week 33, the diet was supplemented with guar. The mean blood glucose level of week 33 was 14% lower than that of week 32 (P less than 0.01) but equal to that of week 34. Mean fluctuations of blood glucose during individual days of the 3 wk were similar. The M-value declined significantly from week 32 to week 33, but the M-value of week 33 was not different from that of week 34. The average 24-h glycosuria declined by 63% from week 32 to week 33 (P less than 0.05), whereas the values of weeks 33 and 34 were not significantly different. The mean daily insulin doses of weeks 32, 33, and 34 were similar. The results show that whereas admission of pregnant insulin-dependent diabetic women to a diabetes ward exerts a favorable influence on diabetes control, no further improvement is obtainable if the diet is supplemented with guar.

Guar gum was incorporated into the diets of six insulin dependent diabetics drawn from one general practice. Amounts between 6 and 59.6 g daily were used for four to six weeks and compared with a previous two week control period. Unlike some other studies, little improvement was obtained in diabetic control and a small reduction in cholesterol levels occurred. The guar was well tolerated in amounts below 30 g a day.

A new type of guar-containing biscuit has been developed and incorporated into the diabetic diet in both short- and medium-term studies. It has been found to be effective in reducing the postprandial rise in the blood glucose level and in improving glycaemic control, as shown by reduced fasting blood glucose values and decreased 24-hour urinary glucose excretion. This form of guar has proved to be palatable and acceptable to patients. It was effective in smaller quantities than have previously been tested and may prove a valuable adjunct in the treatment of diabetes.

Symptoms associated with carbohydrate malabsorption limit the usefulness to diabetics of a powerful glycoside-hydrolase inhibitor (acarbose) which reduces postprandial glycaemia. Addition of a low dose (50 mg) of a acarbose together with 14.5 g guar gum to a breakfast test meal taken by 8 healthy volunteers reduced the mean peak rise in blood-glucose at 30 min by 70%. Areas under the insulin and gastrointestinal-polypeptide response curves were also greatly reduced. No evidence of carbohydrate malabsorption, as assessed by measurement of breath hydrogen, was found during any of the test periods. When acarbose was taken alone, 3 of the 8 subjects had troublesome symptoms and the 30 min rise in blood-glucose was reduced by only 28%. Thus, combination of these two agents effectively reduces the rate of carbohydrate absorption without increasing side-effects and may make combined acarbose and guar acceptable in the management of some diabetics.

High-fibre diets, particularly with the addition of guar gum, have been reported to improve control of blood glucose concentration in diabetics. These studies are reviewed, and the results of a study of 22 obese, poorly controlled, poorly compliant diabetic outpatients are presented. In a random, single-blind controlled trial, either guar, or bran, or placebo were added to the previous diet. Over a three-month period, there were no changes in weight, fasting blood glucose levels, or random blood glucose levels. Problems of tolerance were experienced with guar gum. Therefore, supplementation of the diet of such patients with guar gum or bran does not produce long-term improvements in diabetic control in a clinical context. The use of naturally occurring high-fibre foods may slightly improve diabetic control in motivated patients, but further long-term trials are required to establish whether dietary fibre will have any significant role in the practical management of diabetes.

Two test meals were taken in random order on separate days by 8 non-insulin-requiring diabetic volunteers after 14-hour overnight fasts. Addition of 16 g guar and 10 g pectin to the control meal containing 106 g carbohydrate decreased markedly and significantly the rise in blood-glucose between 30 and 90 minutes and also resulted in significantly lower insulin levels between 30 and 120 minutes. When these meals were fed to 3 insulin-dependent diabetic subjects, a similar flattening of the post-prandial glucose rise ensued. This addition of certain forms of dietary fibre to the diet of diabetics significantly decreases post-prandial hyperglycaemia and would be expected to improve the control of blood-glucose concentration.