RESUMEN
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.
Asunto(s)
Betula , Colesterol , Cricetinae , Masculino , Animales , Mesocricetus , Ácidos y Sales Biliares/metabolismo , Triglicéridos , Pectinas , Hígado/metabolismo , Dieta Alta en Grasa , HecesRESUMEN
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.
Asunto(s)
Crataegus/química , Macrófagos Peritoneales/efectos de los fármacos , Óxido Nítrico/metabolismo , Polisacáridos/farmacología , Animales , Arginasa/efectos de los fármacos , Arginasa/metabolismo , Células Cultivadas , Femenino , Macrófagos Peritoneales/enzimología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Polisacáridos/aislamiento & purificación , Solubilidad , Agua/químicaRESUMEN
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.
Asunto(s)
Conium/metabolismo , Polisacáridos/química , Solubilidad , Agua/química , Alcaloides/metabolismo , Animales , Células Presentadoras de Antígenos , Arginasa/metabolismo , Femenino , Sistema Inmunológico , Linfocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/química , PoaceaeRESUMEN
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.
Asunto(s)
Antineoplásicos Alquilantes/toxicidad , Células de la Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Ciclofosfamida/antagonistas & inhibidores , Células Madre Hematopoyéticas/efectos de los fármacos , Polisacáridos/farmacología , Tussilago/química , Animales , Antígenos CD34/genética , Antígenos CD34/inmunología , Biomarcadores/metabolismo , Médula Ósea/inmunología , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Recuento de Células , Ciclofosfamida/toxicidad , Femenino , Expresión Génica , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Inmunofenotipificación , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Polisacáridos/aislamiento & purificación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/inmunologíaRESUMEN
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.
Asunto(s)
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Polisacáridos/uso terapéutico , Receptor de Muerte Celular Programada 1/metabolismo , Tussilago/química , Animales , Femenino , Citometría de Flujo , Inmunoterapia , Ratones , Ratones Endogámicos C57BLRESUMEN
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.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Polisacáridos/farmacología , Tussilago/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Pulmonar de Lewis/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Eosina Amarillenta-(YS) , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Hematoxilina , Histocitoquímica , Mucosa Intestinal/patología , Irinotecán/administración & dosificación , Irinotecán/efectos adversos , Ratones , Ratones Endogámicos C57BL , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Extractos Vegetales/química , Polisacáridos/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/antagonistas & inhibidores , Células de la Médula Ósea/efectos de los fármacos , ADN/química , Mucosa Intestinal/efectos de los fármacos , Polisacáridos/farmacología , Tussilago/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Cisplatino/antagonistas & inhibidores , Cisplatino/toxicidad , Ensayo Cometa , ADN/metabolismo , Duodeno/citología , Duodeno/efectos de los fármacos , Duodeno/metabolismo , Femenino , Inyecciones Intraperitoneales , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Irinotecán/antagonistas & inhibidores , Irinotecán/toxicidad , Ratones , Ratones Endogámicos C57BL , Paclitaxel/antagonistas & inhibidores , Paclitaxel/toxicidad , Extractos Vegetales/química , Polisacáridos/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Cisplatino/farmacología , Paclitaxel/farmacología , Polisacáridos/farmacología , Tussilago/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/patología , Femenino , Filgrastim/farmacología , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , Granulocitos/patología , Fármacos Hematológicos/farmacología , Recuento de Leucocitos , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Polisacáridos/aislamiento & purificación , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
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.
Asunto(s)
Acorus/química , Antineoplásicos Fitogénicos/administración & dosificación , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Molécula de Adhesión Celular Epitelial/metabolismo , Animales , Antígeno B7-H1/genética , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Molécula de Adhesión Celular Epitelial/genética , Femenino , Ratones Endogámicos C57BL , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ratas , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A screening study of biological activity of native humic acids isolated from peat was performed; several physical and chemical parameters of their structures were studied by UV- and infrared spectroscopy. Spectroscopy yielded similar shape of light absorption curves of humic acids of different origin, which can reflect similarity of general structural principles of these substances. Alkaline humic acids have more developed system of polyconjugation, while molecular structures of pyrophosphate humic acids were characterized by higher aromaticity and condensation indexes. Biological activity of the studied humic acids was assessed by NO-stimulating capacity during their culturing with murine peritoneal macrophages in a wide concentration range. It was shown that due to dose-dependent enhancement of NO production humic acids can change the functional state of macrophages towards development of pro-inflammatory properties. These changes were associated with high activity of humic acids isolated by pyrophosphate extraction, which allows considering effects of isolation method on biological activity.
Asunto(s)
Sustancias Húmicas , Macrófagos Peritoneales/metabolismo , Óxido Nítrico/biosíntesis , Suelo/química , Animales , Células Cultivadas , Evaluación Preclínica de Medicamentos , Femenino , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Ratones Endogámicos C57BLRESUMEN
Screening study of the effects of sweet flag (Acorus calamus L.) rhizome and clover (Trifolium pratense L.) aerial part on the production of NO by mouse macrophages was carried out. The polysaccharides were separated by ion exchange chromatography into fractions differing by monomeric composition and ramification type and were used in concentrations of 20, 40, and 100 µg/ml. Four fractions of Acorus calamus L. (PSF-101, PSF-102, PSF-103, and PSF-105), used in different concentrations, moderately stimulated nitrite production by macrophages. Three of five Trifolium pratense L. polysaccharides (PS62-3, PS62-4, and PS62-5) exhibited a significant specific effect on NO production. Rhamnogalactouronans from clover PS63-3 in all concentrations and from PS62-5 in a concentration of 100 µg/ml exhibited the highest activity, comparable to the NO-stimulatory activity of the reference LPS, while polysaccharide PS62-3 in a concentration of 40 µg/ml exhibited even higher activity.
Asunto(s)
Acorus/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Pectinas/farmacología , Polisacáridos/farmacología , Trifolium/química , Animales , Células Cultivadas , Femenino , Masculino , Ratones , Pectinas/química , Polisacáridos/químicaRESUMEN
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.
Asunto(s)
Macrófagos Peritoneales/inmunología , Óxido Nítrico/inmunología , Extractos Vegetales/farmacología , Plantas/química , Células TH1/inmunología , Animales , Células Cultivadas , Evaluación Preclínica de Medicamentos , Eritrocitos/inmunología , Lipopolisacáridos/farmacología , Macrófagos Peritoneales/enzimología , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa/inmunología , Extractos Vegetales/química , Ovinos , Células TH1/metabolismoRESUMEN
A pectic polysaccharide was isolated from the rhizomes of Acorus calamus L. The main component of its carbohydrate chain was represented by residues of D-galacturonic acid (>85%). In addition, this polysaccharide contained residues of galactose, arabinose, xylose and rhamnose (<10%). Structural analysis of pectic polysaccharide from A.calamus L. with NMR spectroscopy indicated that it contains the regions of a linear 1,4-alpha-D-galactopyranosyluronan, which represents a major component of the macromolecule. A considerable amount of galacturonic acid residues was not methoxylated. We demonstrate here that the pectic polysaccharide from A. calamus L. in low concentrations was able to stimulate in vitro IL-12 and nitric oxide production by murine macrophages. It also induced TNF-alpha secretion by human peripheral blood mononuclear cells, reduced arginase activity but did not affect IL-10 secretion by murine macrophages or human peripheral blood mononuclear cells. The IL-12 and NO-stimulating effects on murine macrophages were similar to that of LPS. In addition, the polysaccharide promoted in vivo Th1 immune response in mice which were immunized with sheep red blood cells (DTH and quantity of plaque-forming cells) and down regulated serum level of IgG1 and IgE during Th2-depend immune response induced by ovalbumin. The PS increased Th1-induced edema and suppressed Th2-induced paw swelling in adoptive systems. Our results suggest that the pectic polysaccharide from A. calamus L. represents a promising immunomodulating agent that stimulates M1-polarized macrophages and promotes Th1-oriented adaptive immune response. We propose that this polysaccharide could be potentially applied for treatment of infectious, oncological diseases or for immunoglobulin-E-mediated disorders.