RESUMO
Centipede is an important traditional Chinese medicine with a long history of clinical application and a wide range of effects, and its use in the field of andrology is also expanding.In this study, the drug experience and clinical research progress of centipede in erectile dysfunction, chronic prostatitis, prostate cancer, varicocele, chronic epididymitis, epididymal nodules, functional non-ejaculation, scrotal eczema and other diseases were reviewed.
Assuntos
Andrologia , Epididimite , Disfunção Erétil , Masculino , Animais , Humanos , Quilópodes , EpididimoRESUMO
A rapid, sensitive, and specific LC-MS/MS method was developed and fully validated for the detection of paeoniflorin only in rat plasma, and applied to pharmacokinetic studies, including intravenous, multi-dose oral and combined administrations with verapamil. In this study, tolbutamide was used as the internal standard, and the protein precipitation extraction method, using acetonitrile as the extraction agent, was used for the sample preparation. Subsequently, the supernatant samples were analyzed on a Phenomenex Gemini® NX-C18 column with a flow rate of 1.0 mL/min in a gradient elution procedure. In the extracted rat plasma, the method exhibited high sensitivity (LLOQ of 1.0 ng/mL) upon selecting ammonium adduct ions ([M+NH4]+) as the precursor ions and good linearity over the concentration range of 1.0−2000 ng/mL, with correlation coefficients >0.99. The intra- and inter-batch accuracy RE% values were within ±8.2%, and the precision RSD% values were ≤8.1% and ≤10.0%, respectively. The results show that the method can be successfully applied to quantitate paeoniflorin in biological samples. Additionally, paeoniflorin is subsequently confirmed to be the substrate of the P-gp transporter in vivo and in vitro for the first time, which would be necessary and beneficial to investigate the clinical safety and efficacy of PF with other drugs in the treatment of rheumatoid arthritis.
Assuntos
Espectrometria de Massas em Tandem , Verapamil , Ratos , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Monoterpenos/farmacocinética , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Heparan sulfate (HS) is a complex linear polysaccharide that modulates a wide range of biological functions. Elucidating the structure-function relationship of HS has been challenging. Here we report the generation of an HS-mutant mouse lung endothelial cell library by systematic deletion of HS genes expressed in the cell. We used this library to (1) determine that the strictly defined fine structure of HS, not its overall degree of sulfation, is more important for FGF2-FGFR1 signaling; (2) define the epitope features of commonly used anti-HS phage display antibodies; and (3) delineate the fine inter-regulation networks by which HS genes modify HS and chain length in mammalian cells at a cell-type-specific level. Our mutant-cell library will allow robust and systematic interrogation of the roles and related structures of HS in a cellular context.
Assuntos
Anticorpos/imunologia , Endotélio Vascular/metabolismo , Epitopos/imunologia , Heparitina Sulfato/química , Heparitina Sulfato/imunologia , Pulmão/metabolismo , Mutação , Animais , Especificidade de Anticorpos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Heparitina Sulfato/genética , Heparitina Sulfato/metabolismo , Pulmão/citologia , Pulmão/imunologia , Camundongos Endogâmicos C57BL , Biblioteca de Peptídeos , Transdução de Sinais , Relação Estrutura-Atividade , Enxofre/químicaRESUMO
Complement-mediated inflammation and tissue damage is an important drive to pathology in autoimmune diseases, targeting inhibit the complement activation is promising treatment strategy for these diseases. We performed anticomplement activity-guided fractionation of the water extract of Eclipta prostrata by ion-exchange and size-exclusion chromatography, yielding two bioactive polysaccharides EAP20-1 and EAP20-2. The molecular weights of EAP20-1 and EAP20-2 were respectively calculated to be 5.2 kDa and 6.3 kDa by HPGPC, both polysaccharides was composed by d-Gal, l-Glc, and Ara at different ratios of 7.3:2.7:1 and 7.6:3.1:1. In addition, the main linkage types of EAP20-1 and EAP20-2 were ß-1,4-Gal, ß-1,6-Gal and α-1,4,6-Glc according to methylation analyses. EAP20-1 and EAP20-2 exhibited significant inhibitory effect on the complement activation through both classical and alternative pathways and with no influence on the coagulation system. Preliminary mechanism study indicated that both EAP20-1 and EAP20-2 inhibited the activation of the complement system by interacting with C1q, C1r, C1s, C2, C4, C5, C7, and C9 components.
Assuntos
Ativação do Complemento/efeitos dos fármacos , Proteínas do Sistema Complemento/imunologia , Eclipta/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Cromatografia em Gel , Polissacarídeos/isolamento & purificação , OvinosRESUMO
Radix Paeoniae Alba is widely used in Chinese traditional medicine to treat various diseases such as gastrointestinal disorders, cancer, and other diseases. In this study, two polysaccharides RPAPW1 and RPAPW2 were isolated from Radix Paeoniae Alba by DEAE-52 cellulose chromatography and G-25 sephadex. According to physicochemical methods, NMR and methylation analysis, RPAPW1 and RPAPW2 were established to be α-glucans consisting of predominant 4-linked α- Glc residues branched at O-6 and contained trace amount of protein and uronic acid. Immunological tests indicated that RPAPW1, RPAPW2 and could promote splenocyte proliferation and RAW264.7 phagocytic activity. In vitro, RPAPW1 and RPAPW2 elicited a week reducing power, DPPH scavenging activity and could not protect the PC12 cells from H2O2 damage. These data implied polysaccharides RPAPW1 and RPAPW2 had the potential to be a natural immunopotentiating and antioxidant supplement for preparing functional foods and nutraceuticals.
Assuntos
Proliferação de Células/efeitos dos fármacos , Paeonia/química , Fagocitose/efeitos dos fármacos , Polissacarídeos , Baço/imunologia , Animais , Linhagem Celular , Masculino , Camundongos , Células PC12 , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ratos , Baço/citologiaRESUMO
According to the potential anti-hepatoma therapeutic effect of Schisandra chinensis polysaccharides presented in previous studies, a bioactive constituent, homogeneous Schisandra chinensis polysaccharide-0-1 (SCP-0-1), molecular weight (MW) circa 69.980 kDa, was isolated and purified. We assessed the efficacy of SCP-0-1 against human hepatocellular liver carcinoma (HepG2) cells to investigate the effects of its antitumour activity and molecular mechanisms. Anticancer activity was evaluated using microscopy, 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 staining, acridine orange (AO) staining, flow cytometry (FCM), and cell-cycle analysis. SCP-0-1 inhibited the HepG2 cells' growth via inducing apoptosis and second gap/mitosis (G2/M) arrest dose-dependently, with a half maximal inhibitory concentration (IC50) value of 479.63 µg/mL. Western blotting of key proteins revealed the apoptotic and autophagic potential of SCP-0-1. Besides, SCP-0-1 upregulated Bcl-2 Associated X Protein (Bax) and downregulated B-cell leukemia/lymphoma 2 (Bcl-2) in the HepG2 cells. The expression of caspase-3, -8, and -9; poly (ADP-ribose) polymerase (PARP); cytochrome c (Cyt C); tumor protein 53 (p53); survivin; sequestosome 1 (p62); microtubule-associated protein 1 light chain-3B (LC3B); mitogen-activated protein kinase p38 (p38); extracellular regulated protein kinases (ERK); c-Jun N-terminal kinase (JNK); protein kinase B (AKT); and heat shock protein 90 (Hsp90) were evaluated using Western blotting. Our findings demonstrate a novel mechanism through which SCP-0-1 exerts its antiproliferative activity and induces mitochondrial apoptosis rather than autophagy. The induction of mitochondrial apoptosis was attributed to the inhibition of the Hsp90/AKT signalling pathway in an extracellular signal-regulated kinase-independent manner. The results also provide initial evidence on a molecular basis that SCP-0-1 can be used as an anti-hepatocellular carcinoma therapeutic agent in the future.
Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Schisandra/química , Apoptose/efeitos dos fármacos , Citocromos c/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células Hep G2 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
G19 is a novel homogeneous sulfated oligosaccharide, prepared from Grateloupia filicina. In the present study, we first reported that oligosaccharide G19 exhibited a dose- and time-dependent anti-proliferation effect against U-87 malignant gliomas (MG) human glioma cells. Further studies indicated that G19 strongly bound to epidermal growth factor (EGF), suppressed EGF receptor phosphorylation and interrupted the phosphatidylinositol-3 kinase/Akt pathway in the cancer cells. Moreover, G19 elevated intracellular reactive oxygen species levels and caused endogenous DNA damage. These actions were associated with activation of ataxia-telangiectasia-mutated/checkpoint kinase 2 pathway. The downregulation of MDM2 with stabilizing p53 and the nuclear location of p21 were induced by G19 to cause cell cycle arrest and apoptosis to some extent. Meanwhile, intrinsic mitochondrial pathway and extrinsic death receptor pathway were involved in G19-mediated apoptosis. Pretreatment with free radical scavenger N-acetyl-l-cysteine nearly completely inversed G19-induced cell growth inhibition, cell cycle arrest and apoptosis in U-87 MG cells. Importantly, G19 could inhibit the growth of U-87 MG tumor cells xenograft in nude mice. The results suggested that G19 could be served as a new targeting drug candidate for human glioma treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Glioma/tratamento farmacológico , Oligossacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioma/metabolismo , Glioma/patologia , Humanos , Terapia de Alvo Molecular , Rodófitas/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Two natural homogalacturonan (HG) pectins (MW ca. 20 kDa) were isolated from green tea based on their immunomodulatory activity. The crude tea polysaccharides (TPS1 and TPS2) were obtained from green tea leaves by hot water extraction and followed by 40% and 70% ethanol precipitation, respectively. Two homogenous water soluble polysaccharides (TPS1-2a and TPS1-2b) were obtained from TPS1 after purification with gel permeation, which gave a higher phagocytic effect than TPS2. A combination of composition, methylation and configuration analyses, as well as NMR (nuclear magnetic resonance) spectroscopy revealed that TPS1-2a and TPS1-2b were homogalacturonan (HG) pectins consisting of a backbone of 1,4-linked α-D-galacturonic acid (GalA) residues with 28.4% and 26.1% of carboxyl groups as methyl ester, respectively. The immunological assay results demonstrated that TPS1-2, which consisted mainly of HG pectins, showed phagocytosis-enhancing activity in HL-60 cells.
Assuntos
Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Pectinas/química , Pectinas/farmacologia , Chá/química , Linhagem Celular , Humanos , Fatores Imunológicos/isolamento & purificação , Metilação , Pectinas/isolamento & purificação , Fagocitose/efeitos dos fármacosRESUMO
Arabinogalactan (AG), a biologically active substance found abundantly in plants, is of significant interest in plant physiology due to its unique physicochemical properties. Yariv reagent, widely utilized in AG-II related applications, forms insoluble precipitates when bound to AG-II. This paper provides a comprehensive overview of the synthesis methods, physicochemical properties, and various dissociation methods of the Yariv reagent to enhance its utility in AG-II studies. Furthermore, the review explores the binding mechanisms and applications of the Yariv reagent, highlighting the advancements in studying the Yariv-AG complex in plant physiology. The aim of this review is to inspire new research ideas and foster novel applications of the Yariv reagent from synthesis to implementation.
Assuntos
Glucosídeos , Floroglucinol , Glucosídeos/química , Glucosídeos/metabolismo , Floroglucinol/química , Fenômenos Fisiológicos Vegetais , Polissacarídeos , Proteínas de Plantas/metabolismo , Mucoproteínas/metabolismoRESUMO
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.
Assuntos
Autoimunidade , Encefalomielite Autoimune Experimental , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Inulina , Camundongos Endogâmicos C57BL , Esclerose Múltipla , Prebióticos , Células Th17 , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Inulina/administração & dosagem , Inulina/farmacologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/microbiologia , Células Th17/imunologia , Camundongos , Prebióticos/administração & dosagem , Feminino , Ácidos Graxos Voláteis/metabolismo , Autoimunidade/efeitos dos fármacos , Esclerose Múltipla/imunologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/microbiologia , Sistema Nervoso Central/imunologia , Bactérias/classificação , Bactérias/isolamento & purificaçãoRESUMO
Secondary lymphedema is a chronic and incurable disease lacking satisfactory therapeutic drugs. It primarily results from lymphatic vessel dysfunction resulting from factors such as tumor-related surgery, injury, or infection. Promoting lymphangiogenesis and lymphatic vessel remodeling is crucial for restoring tissue fluid drainage and treating secondary lymphedema. In this study, we discovered that the oral administration of a type-II arabinogalactan (CAPW-1, molecular weight: 64 kDa) significantly promoted lymphangiogenesis and alleviated edema in mice with secondary lymphedema. Notably, the tail diameter of the CAPW-1200 group considerably decreased in comparison to that of the lymphedema group, with an average diameter difference reaching 0.98 mm on day 14. CAPW-1 treatment also reduced the average thickness of the subcutaneous area in the CAPW-1200 group to 0.37 mm (compared with 0.73 mm in the lymphedema group). It also facilitated the return of injected indocyanine green (ICG) from the tail tip to the sciatic lymph nodes, indicating that CAPW-1 promoted lymphatic vessel remodeling at the injury site. In addition, CAPW-1 enhanced the proliferation and migration of lymphatic endothelial cells. This phenomenon was associated with the activation of the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, thereby promoting the expression of vascular endothelial growth factor-C (VEGF-C), which can be abolished using a TLR4 antagonist. Despite these findings, CAPW-1 did not alleviate the symptoms of lymphedema or restore lymphatic drainage in VEGFR3flox/flox/Prox1-CreERT2 mice. In summary, CAPW-1 alleviates secondary lymphedema by promoting lymphangiogenesis and lymphatic vessel remodeling through the activation of the TLR4/NF-κB/VEGF-C signaling pathway, indicating its potential as a therapeutic lymphangiogenesis agent for patients with secondary lymphedema.
Assuntos
Galactanos , Linfangiogênese , Vasos Linfáticos , Linfedema , Receptor 4 Toll-Like , Animais , Linfangiogênese/efeitos dos fármacos , Camundongos , Linfedema/tratamento farmacológico , Linfedema/metabolismo , Linfedema/etiologia , Vasos Linfáticos/efeitos dos fármacos , Vasos Linfáticos/metabolismo , Galactanos/farmacologia , Galactanos/química , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , NF-kappa B/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , MasculinoRESUMO
Steamed Polygonatum cyrtonema has been commonly used clinically for its gaining effect, whose main active ingredient is a polysaccharide. A water-soluble polysaccharide named PSP-W-1 was isolated from steamed Polygonatum cyrtonema. PSP-W-1 was characterized as a galactan having a backbone consisting predominately of 1,4-ß-linked Galp branched at the C-6 position by T-ß-linked Galp with a molecular weight of 14.4 kDa. PSP-W-1 could inhibit the overproduction of inflammatory factors and inflammatory mediators (iNOS, IL-6, COX-2) in dextran sodium sulfate-induced colitis mice. Oral administration of PSP-W-1 dramatically alleviated colonic pathological damage, repaired the intestinal barrier (occludin and ZO-1) and regulated the intestinal microbiota by increasing the abundance of norank_f_Muribaculaceae, Lactobacillus and norank_f_norank_o_Clostridia UCG-014, while decreasing the abundance of Bacteroides and Escherichia-Shigella to alleviate colitis symptoms. Overall, our findings suggest that PSP-W-1 might be a therapeutic option for both the prevention and treatment of colitis.
Assuntos
Colite , Microbioma Gastrointestinal , Polygonatum , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Intestinos , Vapor , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Colo , Sulfato de Dextrana , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
The present study was designed to observe the protection of Grateloupia filicina polysaccharide (GFP) against hepatotoxicity induced by Dioscorea bulbifera L in mice and its underlying mechanism. GFP was intragastrically (ig) given to mice at various doses. After 6 days, the mice were treated with ethyl acetate extract of Dioscorea bulbifera L (EF, ig). Serum levels of alanine/aspartate aminotransferase (ALT/AST), alkaline phosphatase (ALP), total bilirubin (TB) were measured, and liver histological evaluation was conducted. Furthermore, reductions of liver glutathione (GSH) amount and glutamate cysteine ligase (GCL) activity were tested. The expressions of GCL-c, GCL-m, and HO-1 (heme oxygenase-1) in liver were observed by Western-blot. The results showed that GFP (600 mg x kg(-1)) decreased EF-induced the increase of serum ALT, AST and TB, and GFP (400, 600 mg x kg(-1)) inhibited EF-induced the increase of serum ALP. Liver histological evaluation showed that the liver injury induced by EF was relieved after treated with GFP. GFP further increased liver GSH amount and reversed EF-induced the decrease of GCL activity. The Western-blot result showed that GFP augmented EF-induced the increase of HO-1, and reversed EF-induced the decrease of GCL-c. In conclusion, GFP can act against the oxidative stress liver injury induced by Dioscorea bulbifera L in mice.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dioscorea/toxicidade , Compostos Heterocíclicos de 4 ou mais Anéis/toxicidade , Polissacarídeos/farmacologia , Rodófitas/química , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/antagonistas & inibidores , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Plantas Medicinais/química , Polissacarídeos/isolamento & purificação , Distribuição AleatóriaRESUMO
Pectin exists extensively in nature and has attracted much attention in biological applications for its unique chemical and physical characteristics. Functionalized pectin, especially pectic conjugates, has given many possibilities for pectin to improve its properties and bioactivity as well as to deliver active molecules. To better exploit this strategy of pectic functionalization, this review presents in detail the structural modifications of pectin, different synthetic methods, and design strategies of pectic conjugates involving both traditional chemical and "green" approaches. Here, the research ideas and applications of pectic prodrugs as well as the development of preparation based on pectic conjugates are reviewed, with emphasis on crosslinking systems of functionalized pectin and nanosystems based on self-assembly techniques. We hope this review will provide comprehensive and valuable information for the functionalization and systematization of the pectic conjugate from synthesis to application.
Assuntos
Pectinas , Pectinas/químicaRESUMO
The pollen of Typha angustifolia L. decoction was clinically used to treat hyperlipidemia in China. A pectin polysaccharide (PTPS-2-2) was obtained from T. angustifolia pollen through water extraction, ion-exchange chromatography, and gel chromatography. Structural characterization showed that PTPS-2-2 had a molecular weight of 54 kDa and was composed of rhamnose, arabinose, xylose, galactose, and galacturonic acid with a molar ratio of 11.5: 36.5: 4.1: 36.7: 11.2. PTPS-2-2 consisted of rhamnogalacturonan I (RG-I) and arabinogalactan II (AG-II) domains. Its backbone was predominantly composed of â4-α-D-GalpA-(1 â 2)-α-L-Rhap-(1â, with branches of 1,3-Galp, 1,6-Galp, 1,3,6-Galp, T-Araf, 1.5-Araf and T-Xylp, connected to the 4-position of 1,2-Rhap and the 3-position of 1,4-GalpA. The inhibitory effect of PTPS-2-2 on lipid accumulation was studied in vitro, using L02 cells induced by oleic acid. This experiment shows that PTPS-2-2 treatment at 100-400 µg/mL dose-dependently reduce cellular triglycerides (TG), cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, while elevated superoxide dismutase (SOD) levels. This indicated that PTPS-2-2 potentially ameliorated oleic acid-induced hepatic steatosis by inhibiting lipid accumulation and oxidative stress.
Assuntos
Ácido Oleico , Typhaceae , Pectinas/farmacologia , Pectinas/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Galactose/químicaRESUMO
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by inflammation and hepatic steatosis that may coincide with fibrotic activity. To date, no pharmacological agents have been approved for NASH treatment. Here, a homogeneous (1,3),(1,6)-ß-D-glucan (PUP-W-1, Mw: 41.07 kDa) was successfully purified from Polyporus umbellatus (Pers.) Fries sclerotia and characterized. The analysis showed that the PUP-W-1 backbone consisted of a repeating chain of eight â3)-ß-D-Glcp-(1 â units, with branched chains of four ß-D-Glcp residues, joined by repeating 1,6-linkage units at the O-6 position of the backbone. The pharmacological effects of PUP-W-1 treatment in the context of NASH pathogenesis were explored using a methionine choline-deficient (MCD) diet-induced murine steatohepatitis model. The MCD model mice exhibited pronounced steatohepatitis, inflammatory activity, steatosis, stellate cell activation, and mild fibrotic activity. Treatment of the mice for three weeks with PUP-W-1 prevented the development of NASH due to the suppression of inflammation, lipid accumulation, and fibrosis. As suggested by these findings, PUP-W-1 may hold promise as a natural drug candidate or precursor for the treatment of NASH.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Polyporus , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/patologia , Glucanos/farmacologia , Polyporus/química , Dieta , Colina/análise , Metionina/análise , Inflamação/patologia , Camundongos Endogâmicos C57BL , FígadoRESUMO
An arabinogalactan (PTPS-1-2) was isolated and characterized from Pollen Typhae, and its potential antitumor effects on activating macrophages to produce immunomodulatory factors and promoting apoptosis in colorectal cancer cells were investigated. Structural characterization showed that PTPS-1-2 had a molecular weight of 59 kDa and was composed of rhamnose, arabinose, glucuronic acid, galactose, and galacturonic acid with a molar ratio of 7.6: 17.1: 6.5: 61.4: 7.4. Its backbone was predominantly composed of T-ß-D-Galp, 1,3-ß-D-Galp, 1,6-ß-D-Galp, 1,3,6-ß-D-Galp, 1,4-α-D-GalpA, 1,2-α-L-Rhap, additionally, branches contained 1,5-α-L-Araf, T-α-L-Araf, T-ß-D-4-OMe-GlcpA, T-ß-D-GlcpA and T-α-L-Rhap. PTPS-1-2 activated RAW264.7 cell by triggering the NF-kB signaling pathway and M1 macrophage polarization. Furthermore, the conditioned medium (CM) of Mφ pretreated with PTPS-1-2 exerted marked antitumor effects by inhibiting RKO cell proliferation and suppressing cell colony formation. Collectively, our findings suggested that PTPS-1-2 might be a therapeutic option for the prevention and treatment of tumors.
Assuntos
Apoptose , Galactanos , Macrófagos , Galactose , Animais , Camundongos , Células RAW 264.7RESUMO
The genus Polygonatum is gaining increasing attention from nutrition experts as well as health-conscious consumers because of its excellent performance in providing nutrients. Among these plants, Polygonatum sibiricum and Polygonatum odoratum have been selected for inclusion in China's Medicinal Food Directory due to their high safety profile. Polysaccharides are considered the main functional component and one of the main active ingredients of the plant. In addition, polysaccharides from genus Polygonatum have a variety of nutritional, biological and health-promoting properties, such as immunomodulatory, anti-inflammatory, cardiovascular protective, neuroprotective, antitumor, antidiabetic, antiosteoporosis, and hepatoprotective properties. This paper reviews the origin, extraction, purification, structural characteristics, biological activity, safety, toxicological evaluation, and structure-activity relationship of polysaccharides from the genus Polygonatum. Ultimately, we hope that this work can provide a more useful reference for understanding the polysaccharide structure and developing of new functional foods from polysaccharides of the genus Polygonatum.
Assuntos
Polygonatum , Polygonatum/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Antioxidantes/química , Imunomodulação , HipoglicemiantesRESUMO
A water-soluble polysaccharide CSPS-2B-2 with a molecular mass of 8.8 kDa, was obtained from the fruits of Capparis spinosa L. Chemical and NMR spectral analysis verified CSPS-2B-2 was a linear poly-(1-4)-α-D-galactopyranosyluronic acid in which 12.9±0.4% of carboxyl groups existed as methyl ester and 2.6±0.1% of D-GalpA residues were acetylated. A sulfated derivative Sul-2B-2 with a sulfation degree of 0.88±0.02 was prepared via the substitution of C-2 and/or C-3 of GalpA residues in CSPS-2B-2. Bioassay on the complement and coagulation system demonstrated that Sul-2B-2 (CH(50): 3.5±0.2 µg/mL) had a stronger inhibitory effect on the activation of complement system through the classic pathway than that of heparin (CH(50): 8.9±0.3 µg/mL). Interestingly, Sul-2B-2 at low dose even middle dose (for example 52 µg/mL) had no effect on coagulation system, which was totally different from heparin. Thus, our observation indicated that Sul-2B-2 was more efficient than heparin in inhibiting the activation of the complement system through classical pathway and exhibiting a relatively less anti-coagulant activity. These results suggested that the sulfated derivative Sul-2B-2 prepared from the homogalacturonan in the fruits of Capparis spinosa L, might be a promising drug candidate in case of necessary therapeutic complement inhibition.
Assuntos
Capparis/química , Inativadores do Complemento/química , Proteínas do Sistema Complemento/química , Frutas/química , Pectinas/química , Ésteres do Ácido Sulfúrico/química , Animais , Anticoagulantes/química , Coagulação Sanguínea , Cromatografia , Inativadores do Complemento/isolamento & purificação , Proteínas do Sistema Complemento/metabolismo , Eritrócitos/química , Heparina/química , Espectroscopia de Ressonância Magnética , Pectinas/isolamento & purificação , Extratos Vegetais/química , Coelhos , OvinosRESUMO
Dendrobium officinale Kimura et Migo has been used as a traditional Chinese medicine (TCM) and a functional food for thousands of years. Carbohydrate is one of the most important effective substances and indicative components in D. officinale. However, since the qualitative and quantitative analysis of polysaccharides in D. officinale remains a challenge and limitation, herein, an oligosaccharide-quality marker approach was newly developed for quality assessment of D. officinale by spectrum-effect relationships between high performance liquid chromatographic (HPLC) fingerprints and anti-inflammatory effects. The HPLC fingerprints of 48 batches of oligosaccharides from D. officinale (DOOS) were developed and analyzed with similarity analysis (SA) and hierarchical cluster analysis (HCA), and eight common peaks were identified. In vitro screening experiment indicated that DOOS potentially inhibited nitric oxide (NO) production and effectively reduced the release of inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß in RAW 264.7 cells, thereby reducing the inflammatory response of cells. Finally, the HPLC fingerprint of different batches of DOOS was combined with in vitro anti-inflammatory activity to assess the spectrum-effect relationships of DOOS by gray correlation analysis (GCA), in addition, the purified oligosaccharide components were identified and validated for NO inhibitory activity. Our results showed four DOOS (maltotetraose, maltopentaose, maltohexaose, and mannohexaose) were relevant to anti-inflammatory effects and could be as quality markers for the quality control of D. officinale. It suggests that the "oligosaccharide-spectrum-effect" relationships approach is a simple and reliable method for the quality control of herb medicines or nutritious foods.