ABSTRACT
The presence of anti-polyethylene glycol (PEG) antibodies can limit the clinical efficacy of PEGylated drugs and cause anaphylactic reactions in patients. Monocytes/macrophages are effector cells involved in IgG-mediated passive systemic anaphylaxis. We studied the influence of human blood serum on the efficiency of uptake of PEGylated nanoparticles by human blood monocytes. It has been shown that magnetic nanoparticles modified with PEG-3000 and solid lipid nanoparticles containing PEG-2000 are avidly internalized by human blood monocytes in vitro, the uptake efficiency depends on the features (composition) of donor blood serum, but does not correlate with the level of the IgG antibody against PEG.
Subject(s)
Nanoparticles , Serum , Humans , Monocytes , Immunoglobulin G , Polyethylene GlycolsABSTRACT
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 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
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
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 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
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
Tumor cells can maintain their growth via immunosuppression and escape from host antitumor immunity by controlling the PD-1/PD-L1 system. Expression of PD-L1 (CD274) is an inhibitory signal for T cells, while the increase in CD326 expression in the tumor tissue correlates with metastasis development. The experimental preparation on the basis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan from Acorus calamus L. produces an antitumor effect: it reduces tumor node size and the number and area of metastases after transplantation of Lewis lung carcinoma. Using flow cytometry, we demonstrated a decrease in the population of tumor cells expressing surface CD274 (PD-L1) and CD326 antigens after 20-day course of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan.
Subject(s)
Acorus/chemistry , Antineoplastic Agents, Phytogenic/administration & dosage , B7-H1 Antigen/metabolism , Carcinoma, Lewis Lung/drug therapy , Epithelial Cell Adhesion Molecule/metabolism , Animals , B7-H1 Antigen/genetics , Carcinoma, Lewis Lung/metabolism , Carcinoma, Lewis Lung/pathology , Cell Line, Tumor , Epithelial Cell Adhesion Molecule/genetics , Female , Mice, Inbred C57BL , Plant Extracts/pharmacology , Plant Roots/chemistry , Rats , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
The pharmacological properties of plant polysaccharides are reviewed and original experimental data on the properties of water-soluble polysaccharides isolated from Acorus calamus L. are presented. The possibility of using plant (in particular, Acorus calamus) polysaccharides to increase the effectiveness of anticancer treatment of transferred tumors and to reduce the toxic effects of cytostatic treatment on the normal cells of blood, liver, and epithelium of thin intestine in experimental animals has been demonstrated.
Subject(s)
Acorus/chemistry , Antineoplastic Agents/therapeutic use , Cytotoxins/therapeutic use , Neoplasms/drug therapy , Polysaccharides/therapeutic use , Animals , Antineoplastic Agents/chemistry , Cytotoxins/chemistry , Humans , Polysaccharides/chemistryABSTRACT
Mutagenic properties of water soluble polysaccharides (WSPS) extracted from Acorus calamus L. have been studied. Neither a single intravenous injection nor a course intraperitoneal introduction of WSPS in a dose of 1/2 LD50 to mice of the CBA/CaLac line increases the level of cytogenetic disorders in the bone marrow cells. The investigation of WSPS by means of the somatic mosaicism test showed that the given dose of WSPS does not increase the rate of mutant spots on Drosophila wings.
Subject(s)
Acorus/chemistry , Chromosome Aberrations/chemically induced , Mutagens/chemistry , Mutagens/toxicity , Polysaccharides/chemistry , Polysaccharides/toxicity , Animals , Drosophila melanogaster , Mice , SolubilityABSTRACT
We have studied the influence of water-soluble polysaccharides isolated from Tussilago farfara L. leaves, Betula verrucosa Ehrh. leaves, Calendula officinalis L. flowers, Acorus calamus rhizomes, Inula helenium L. rhizomes, overground part of Trifolium pretense L., and overground part ofArtemisia absinthium L., on Thl immune response induced by sheep red blood cells and on NO production by murine peritoneal macrophages in vitro. All the investigated polysaccharides have stimulated a Th1 response. Polysaccharides isolated from Betula verrucosa leaves did not influence NO synthesis, while polysaccharides of Tussilago farfara leaves and Acorus calamus rhizomes stimulated NO synthase of murine macrophages on a level comparable with that of lipopolysaccharides (LPS). Polysaccharides from Inula helenium rhizomes, Calendula officinalis flowers, and overground parts of Trifolium pretense and Artemisia absinthium also stimulated NO production, but to a lower extent in comparison to LPS.
Subject(s)
Macrophages, Peritoneal/immunology , Nitric Oxide/immunology , Plant Extracts/pharmacology , Plants/chemistry , Th1 Cells/immunology , Animals , Cells, Cultured , Drug Evaluation, Preclinical , Erythrocytes/immunology , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/enzymology , Mice , Mice, Inbred BALB C , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase/immunology , Plant Extracts/chemistry , Sheep , Th1 Cells/metabolismABSTRACT
Experiments on C57LB/6 mice with transplanted Luis lung carcinoma showed that the officinal Echinacea purpurea preparation did not influence the efficacy of cytostatic therapy. This echinacea preparation did not change the development of metastases and even stimulated the tumor growth. In contrast, a hydrophilic polysaccharide complex isolated from echinacea increased the antitumor and antimetastatic activity of cyclophosphamide.
