ABSTRACT
Substances of silver nanoparticles dialyzed through a 13 kDa membrane, synthesized in a medium of humic ligands modified with hydroquinone and 2-hydroxynaphthoquinone from PowHumus brown coal, specifically enhance the M2 properties of peritoneal macrophages due to inhibition of NO synthase and significant activation of arginase, thus enhancing anti-inflammatory properties of cells. In small, but effective concentrations, they do not have cytotoxic properties and do not contain pyrogenic impurities. The studied humates are able to influence the mechanisms of immune response formation and are an effective means for correcting inflammation and regeneration.
Subject(s)
Arginase , Arginine , Humic Substances , Macrophages, Peritoneal , Silver , Animals , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/metabolism , Mice , Arginine/pharmacology , Arginine/chemistry , Arginase/metabolism , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Hydroquinones/pharmacology , Hydroquinones/chemistry , Male , Nitric Oxide/metabolism , Nitric Oxide Synthase/metabolism , Naphthoquinones/pharmacology , Naphthoquinones/chemistryABSTRACT
Humic acids isolated by sodium pyrophosphate extraction from various types of peat activate macrophages in the classical proinflammatory pathway and stimulate nitric oxide production by these cells. This effect is mediated by activation of intracellular signaling pathways involving MAPK p38, PI3K, MEK 1/2 kinase, cAMP, and NF-κB via TLR-2 and TLR-4 receptors.
Subject(s)
Humic Substances , Soil , Macrophage Activation , Nitric Oxide Synthase Type II/metabolism , Signal Transduction , NF-kappa B/metabolism , Nitric Oxide/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Lipopolysaccharides/pharmacologyABSTRACT
The effect of humic acids and substances with similar action - derivatives of succinic acid (ethylmethylhydroxypyridine succinate) and combined agent consisting of succinic acid, nicotinamide, riboflavin, and riboxin on the performance and stress resistance of experimental rats was studied. Performance was assessed in the test of exhaustive forced swimming with a load, stress resistance was evaluated by the serum level of corticosterone and open field behavior, and the state of anaerobic metabolism was estimated by the serum level of lactate after swimming test. Humic acids from peat showed anti-stress activity comparable to that of the officinal preparation and preventive effect on fatigue during physical exercise. They can be recommended as a component for the development of drugs that increase human performance and stress resistance.
Subject(s)
Humic Substances , Soil , Rats , Humans , Animals , Humic Substances/analysis , Succinic Acid , Fatigue , SwimmingABSTRACT
In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.
Subject(s)
Betula , Cholesterol , Cricetinae , Male , Animals , Mesocricetus , Bile Acids and Salts/metabolism , Triglycerides , Pectins , Liver/metabolism , Diet, High-Fat , FecesABSTRACT
The course administration of humic acids isolated by the sodium pyrophosphate method from pine-sphagnum-cotton sedge peat reduced the general anaphylaxis reaction in mice and guinea pigs immunized with ovalbumin and decreased serum content of IgG1 and IgE in mice. The serum from mice treated with humic acids and sensitized with ovalbumin did not increase the rate of degranulation of mast cells isolated from intact Wistar rats in the presence of ovalbumin in comparison with the serum of control animals.
Subject(s)
Anti-Allergic Agents , Sphagnopsida , Animals , Anti-Allergic Agents/pharmacology , Cell Degranulation , Guinea Pigs , Humic Substances , Immunoglobulin E , Mast Cells , Mice , Ovalbumin , Rats , Rats, Wistar , SoilABSTRACT
The course administration of humic acids isolated with sodium pyrophosphate from raised bog sphagnum peat reduces the parameters of a Th1-type immune response in C57BL/6 mice, the severity of an anaphylactic shock in outbred CD1 mice, and degranulation of mast cells after their immunization with ovalbumin. The addition of humic acids increases the stimulated production of IL-4, IL-10 and reduces the production of IL-2, IFNγ by peripheral blood mononuclear cells of healthy donors.
Subject(s)
Humic Substances , Sphagnopsida , Mice , Animals , Humic Substances/analysis , Soil , Leukocytes, Mononuclear/chemistry , Wetlands , Mice, Inbred C57BL , Immunity , Th2 Cells , Cytokines , Th1 CellsABSTRACT
The in vitro addition of water-soluble polysaccharides isolated from the leaves of Crataegus sanguinea Pall. to culture of mouse peritoneal macrophages induced classical activation of antigen-presenting cells by increasing NO synthase activity and reducing arginase expression.
Subject(s)
Crataegus/chemistry , Macrophages, Peritoneal/drug effects , Nitric Oxide/metabolism , Polysaccharides/pharmacology , Animals , Arginase/drug effects , Arginase/metabolism , Cells, Cultured , Female , Macrophages, Peritoneal/enzymology , Macrophages, Peritoneal/metabolism , Mice , Mice, Inbred C57BL , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Polysaccharides/isolation & purification , Solubility , Water/chemistryABSTRACT
Humic acids extracted with sodium pyrophosphate from Oligotrophic Sphagnum magellanicum peat reduce mitogen-stimulated production of anti-inflammatory cytokine IL-10 by mouse peritoneal macrophages and do not affect the secretion of IL-4 by lymphocytes. The studied humic acid sample stimulates the production of proinflammatory cytokines IL-12, TNFα, IL-1ß, and IFNγ by immunocompetent mouse cells and human mononuclear cells. Course administration of humic acids to mice enhances the humoral immunity, increasing the number of antibody-forming cells in the spleen and the titer of antibodies in the blood serum after immunization with sheep red blood cells.
Subject(s)
Humic Substances , Soil , Animals , Interleukin-12/metabolism , Interleukin-1beta/metabolism , Macrophages, Peritoneal/metabolism , Mice, Inbred C57BL , Sphagnopsida/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes 99mТÑ-DPAH-UBI29-41 and 99mТÑ-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%. Accumulation of the complexes in the focus of bacterial inflammation in bone structures and the absence of this complex in the site of aseptic inflammation was confirmed in a rat model of traumatic osteomyelitis by single-photon emission computed tomography.
Subject(s)
Osteomyelitis/drug therapy , Pore Forming Cytotoxic Proteins/chemistry , Ribosomal Proteins/chemistry , Technetium/chemistry , Animals , Diagnosis, Differential , Female , Rats , Rats, Wistar , Tomography, Emission-Computed, Single-PhotonABSTRACT
Addition of water-soluble polysaccharides isolated from Conium maculatum L. to the mouse peritoneal macrophage culture induces classical activation of antigen-presenting cells due to an increase in NO synthase activity and a decrease in arginase expression.
Subject(s)
Conium/metabolism , Polysaccharides/chemistry , Solubility , Water/chemistry , Alkaloids/metabolism , Animals , Antigen-Presenting Cells , Arginase/metabolism , Female , Immune System , Lymphocytes/metabolism , Mice , Mice, Inbred C57BL , Nitric Oxide/chemistry , PoaceaeABSTRACT
Myelotoxicity is a serious side effect of anticancer drugs. The search for drugs that can reduce the hematological complications of chemotherapy through modulation of hematopoietic stem cells is an urgent task of oncopharmacology. In the present study we showed that administration of Tussilago farfara L. polysaccharides to C57BL/6 mice treated with cyclophosphamide can increase the number of hematopoietic stem cells (CD117+34+) in the bone marrow.
Subject(s)
Antineoplastic Agents, Alkylating/toxicity , Bone Marrow Cells/drug effects , Bone Marrow/drug effects , Cyclophosphamide/antagonists & inhibitors , Hematopoietic Stem Cells/drug effects , Polysaccharides/pharmacology , Tussilago/chemistry , Animals , Antigens, CD34/genetics , Antigens, CD34/immunology , Biomarkers/metabolism , Bone Marrow/immunology , Bone Marrow Cells/cytology , Bone Marrow Cells/immunology , Cell Count , Cyclophosphamide/toxicity , Female , Gene Expression , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/immunology , Immunophenotyping , Injections, Intraperitoneal , Mice , Mice, Inbred C57BL , Plant Extracts/chemistry , Polysaccharides/isolation & purification , Proto-Oncogene Proteins c-kit/genetics , Proto-Oncogene Proteins c-kit/immunologyABSTRACT
The study substantiated the possibility of using peat humic acids for improving endurance during extreme physical exertion. The mature outbred Wistar rats weighing 200-250 g (n=40) were subjected to forced swim test until complete exhaustion. The humic acids (1%) were administered intragastrically (0.5 ml/100 g body weight) 30 min prior to the test. Chronic administration of peat humic acids for 5 days increased physical capacity and endurance of rats in exhaustive forced swim test without the changes in serum lactate and corticosterone.
Subject(s)
Biological Factors/pharmacology , Humic Substances/analysis , Physical Conditioning, Animal/physiology , Physical Endurance/drug effects , Physical Exertion/drug effects , Soil/chemistry , Animals , Corticosterone/blood , Gastric Absorption/physiology , Lactic Acid/blood , Male , Physical Endurance/physiology , Rats , Rats, Wistar , Swimming/physiologyABSTRACT
One of prospective methods for immunotherapy of tumors is modulation via immunological checkpoints, specifically, via the PD-1(CD279)/PD-L1(CD274) system. Interactions between tumor cell receptor (CD279) and the ligand on lymphocytes (CD274) leads to lymphocyte inactivation, which allows tumor escape from the immune control. Experiments on C57BL/6 mice with Lewis lung carcinoma demonstrate the possibility of reducing the expression of CD279 and CD274 on the peripheral blood and tumor tissue lymphocytes under the effects of Tussilago farfara L. polysaccharides. This phenomenon can underlie the antitumor and antimetastatic effects of these substances.
Subject(s)
B7-H1 Antigen/metabolism , Carcinoma, Lewis Lung/drug therapy , Carcinoma, Lewis Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Polysaccharides/therapeutic use , Programmed Cell Death 1 Receptor/metabolism , Tussilago/chemistry , Animals , Female , Flow Cytometry , Immunotherapy , Mice , Mice, Inbred C57BLABSTRACT
A course of treatment with humic acids extracted with sodium pyrophosphate from high-moor pine-peat moss-cotton grass peat improves humoral immune response of C57BL/6 mice, stimulates the production of TNFα, IL-1ß, and IL-12 by the animal peritoneal macrophages and the production of IFNγ and TNFα by donor peripheral blood mononuclears, causing no changes in the production of IL-10 in vitro.
Subject(s)
Cytokines/metabolism , Humic Substances , Immunity, Humoral/drug effects , Animals , Cells, Cultured , Humans , Humic Substances/analysis , Immunity, Humoral/physiology , Immunocompetence/drug effects , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred C57BL , Pinus/chemistry , Poaceae/chemistry , Sphagnopsida/chemistryABSTRACT
A possibility for correction of damaging effects of polychemotherapy on the intestinal epithelium with Tussilago farfara L. polysaccharides was studied on C57Bl/6 mice with Lewis lung carcinoma. The polysaccharides had protective and/or stimulating effects on the intestinal epithelium during polychemotherapy and promoted reparative regeneration in the intestine.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Lewis Lung/drug therapy , Intestinal Mucosa/drug effects , Polysaccharides/pharmacology , Tussilago/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Lewis Lung/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Eosine Yellowish-(YS) , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Hematoxylin , Histocytochemistry , Intestinal Mucosa/pathology , Irinotecan/administration & dosage , Irinotecan/adverse effects , Mice , Mice, Inbred C57BL , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Plant Extracts/chemistry , Polysaccharides/isolation & purificationABSTRACT
Prions are proteins that can exist under the same conditions in two or more conformations, at least one of them is infectious. Usually, acquisition of infectious prion conformation is associated with the formation of amyloids - protein aggregates with a characteristic spatial structure. About 10 prions have been identified in the yeast Saccharomyces cerevisiae. The Gln3 protein, which is one of the key regulators of nitrogen metabolism in S. cerevisiae, contains an amyloidogenic region manifesting prion-like properties. The prion properties of the full-length Gln3 have not been studied. We have found that the amyloidogenic region of Gln3 acts as a template and initiates aggregation of the full-length Gln3 in the presence of the [PIN+] prion when Gln3 is overexpressed. Full-length Gln3 in its aggregated form manifests prion-like properties, including infectivity and dependence on the anti-prion agents; however, unlike other known yeast prions, prion-like state of Gln3 is observed only upon the protein overproduction. Here, we suggest the term "conditional prions" for proteins, whose prion state is maintained exclusively under non-physiological conditions.
Subject(s)
Prions/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Transcription Factors/metabolism , Drug Resistance, Fungal/drug effects , Metallothionein/genetics , Microscopy, Confocal , Protein Aggregates/physiology , Saccharomyces cerevisiae Proteins/genetics , Sirolimus/pharmacology , Transcription Factors/geneticsABSTRACT
The cardioprotective and inotropic effects of standardized active natural substance based on high-molecular-weight compounds of humic origin were studied on the model of global ischemia (40 min) and reperfusion of isolated perfused rat heart. Preventive administration of the test substance (0.1 mg/ml) before ischemia/reperfusion modeling reduced reperfusion contracture and necrotic death of cardiomyocytes and promoted recovery of myocardial contractility. Blockade of NO synthase with L-NAME (100 µM) abolished the above effects of the test substance. It was hypothesized that NO synthase plays an important role in the development of the cardioprotective and inotropic effects of the test natural substance.
Subject(s)
Ischemia/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Nitric Oxide Synthase/metabolism , Animals , Heart , Humic Substances , Ischemia/genetics , Male , Myocardial Reperfusion Injury/genetics , NG-Nitroarginine Methyl Ester/metabolism , Nitric Oxide Synthase/genetics , Rats , Rats, WistarABSTRACT
Using DNA comet assay we found that polysaccharides from Tussilago farfara L. reduced the intensity of polychemotherapy-induced apoptosis and DNA damage in bone marrow cells and small intestinal epithelium of C57Bl/6 mice, which attested to genoprotective properties of these polysaccharides.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/antagonists & inhibitors , Bone Marrow Cells/drug effects , DNA/chemistry , Intestinal Mucosa/drug effects , Polysaccharides/pharmacology , Tussilago/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Combined Chemotherapy Protocols/toxicity , Apoptosis/drug effects , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cisplatin/antagonists & inhibitors , Cisplatin/toxicity , Comet Assay , DNA/metabolism , Duodenum/cytology , Duodenum/drug effects , Duodenum/metabolism , Female , Injections, Intraperitoneal , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Irinotecan/antagonists & inhibitors , Irinotecan/toxicity , Mice , Mice, Inbred C57BL , Paclitaxel/antagonists & inhibitors , Paclitaxel/toxicity , Plant Extracts/chemistry , Polysaccharides/isolation & purificationABSTRACT
The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Lewis Lung/drug therapy , Cisplatin/pharmacology , Paclitaxel/pharmacology , Polysaccharides/pharmacology , Tussilago/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Carcinoma, Lewis Lung/immunology , Carcinoma, Lewis Lung/pathology , Female , Filgrastim/pharmacology , Granulocytes/drug effects , Granulocytes/immunology , Granulocytes/pathology , Hematologic Agents/pharmacology , Leukocyte Count , Mice , Mice, Inbred C57BL , Plant Extracts/chemistry , Polysaccharides/isolation & purification , Treatment Outcome , Tumor Burden/drug effectsABSTRACT
Prion and some other incurable human neurodegenerative diseases are associated with misfolding of specific proteins, followed by the formation of amyloids. Despite the widespread usage of the transmission electron and of the atomic force microscopy for studing such amyloids, many related methodological issues still have not been studied until now. Here, we consider one of the first amyloids found in Saccharomyces cerevisiae yeast, i.e. Sup35NMp, to study the adsorption of monomeric protein and its fibrils on the surface of mica, silica, gold and on formvar film. Comparison of linear characteristics of these units calculated by processing of images obtained by the atomic force, transmission and scanning electron microscopy was carried out. The minimal number of measurements of fibril diameters to obtain the values in a given confidence interval were determined. We investigated the film formed by monomeric protein on mica surface, which veiled some morphology features of fibrils. Besides, we revealed that parts of the Sup35NMp excluded from the fibril core can form a wide "coat". The length of the protein forming the core of the fibrils was estimated.