Dendritic cell-targeting polymer nanoparticle-based immunotherapy for cancer: A review.

Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems.

Highly efficient synthesis and antitumor activity of monosaccharide saponins mimicking components of Chinese folk medicine Cordyceps sinensis.

Ergosterol 3-O-ß-D-glucopyranoside (1a) and ergosterol 3-O-ß-D-galactopyranoside (1b) were highly efficiently synthesized and evaluated for their inhibitory activities against two tumor cell lines. The structures of these compounds were extensively confirmed by (1)H, (13)C NMR, IR, and HRMS. Compounds 1a and 1b exhibited interesting cytotoxic profiles. The antitumor activity of compound 1a was higher than that of 1b.

The chromatographic analysis of oligosaccharides and preparation of 1-kestose and nystose in yacon.

The thin-layer chromatographic analysis of the crude oligosaccharides extracted from yacon revealed the presence of glucose, fructose, sucrose, 1-kestose and nystose. The qualitative and quantitative analysis was carried out on oligosaccharides by high pressure liquid chromatography and the results showed that the contents of d-glucose, fructose, sucrose, 1-kestose, nystose and 1-fructofuranosyl nystose in oligosaccharides were 38.30%, 16.44%, 14.58%, 12.29%, 12.17%, 6.20%, respectively. The content of the fructooligosaccharides in oligosaccharides was 30.66%. The crude oligosaccharides were separated and purified by silica gel column chromatography. The two fractions obtained from crude oligosaccharides were 1-kestose and nystose, which were identified by mass spectra. The yield of 1-kestose and nystose were 10.36% and 9.73%, respectively. The purity of 1-kestose was 82.9% and of nystose was 73.6%.

Chemical analysis of a polysaccharide from Cristaria plicata (Leach).

A polysaccharide (MPS) isolated from Cristaria plicata (Leach) consisted of d-glucose. Its structural characteristics were investigated by High Performance Liquid Chromatography (HPLC), infrared analysis, gas chromatography-MS, total acid hydrolysis, methylation analysis, periodate oxidation and Smith degradation. The results indicated that the polysaccharide of C. plicata (Leach) has the weight-average molecular weight of about 2.97 × 106 Da. The structure of the polysaccharide was composed of glucose with α-(1 → 4)-linkages with short exterior chains. The fundamental information obtained from this work is beneficial to the interpretation in the relationship of the polysaccharide structure and its biological functions, and suggests that the polysaccharide from mussel may contribute to be used as a dietary supplement for health foods and therapeutics.

Immunomodulatory effect of polysaccharides from submerged cultured Cordyceps gunnii.

CONTEXT: The genus Cordyceps (Clavicipitaceae) is a group of entomopathogenic fungi that is widely used as tonic food or invigorant with broad-spectrum medicinal properties in China. Cordyceps gunnii (Berk.)Berk (C. gunnii), is also well known as the Chinese rare caterpillar fungus and has similar pharmacological activities with Cordyceps sinensis (C. sinensis). Polysaccharides (PS) from various Cordyceps species have demonstrated many interesting biological activities, including antitumor, immunopotentiation, hypoglycemic, and hypocholesterolemic activities. OBJECTIVE: To investigate the effect of C. gunnii PS on the immunostimulatory antitumor function and expression of immune related cytokines in normal, immuno-suppressive, and H22-bearing mice, respectively. METHODS: C. gunnii PS were extracted with hot water at 80°C for 2 h. Normal, immuno-suppressive, and H22-bearing mice were treated with PS respectively. By detecting the value of macrophage phagocytic index, proliferation of lymphocytes, natural killer (NK) cell activity and expression of related cytokines, interleukin (IL-4), tumor necrosis factor-α (TNF-a) and interferon-γ (IFN-γ), and tumor inhibition index in H22-bearing mice additionally, the effect of PS on immunostimulatory antitumor function and its mechanism were studied. RESULTS: The total sugar content of the PS was determined to be 95% after purification. PS markedly increased the thymus and spleen indexes, the macrophage phagocytosis, the proliferation of splenic cells, and the level of IFN-γ and TNF-α. In tumor growth inhibition test, PS showed remarkable inhibition effects. CONCLUSION: PS from the C. gunnii could enhance nonspecific immunological function, humoral immunity, cellular immunity in mice, and inhibit tumor growth.

Phenolic compounds in the leaves of Populus ussuriensis and their antioxidant activities.

Two new phenolic glucosides [isograndidentatin A (1) isograndidentatin B (2)], 5 known phenolic glucosides [grandidentatin (3), salireposide (4), populoside (5), populoside A (6), and salicortin (7)], and 2 known phenolic acids [P-coumaric acid (8) and caffeic acid (9)] were isolated from the leaves of Populus ussuriensis. Structure elucidation of 1 and 2 was achieved through extensive spectroscopic techniques. Compounds 1-6 and 9 showed significant antioxidant activities, which were evaluated by the DPPH radical-scavenging method (IC(50) values of 6.68, 6.61, 6.75, 6.84, 6.76, 6.79, and 5.92 microM, respectively) and the ABTS .+ radical-scavenging system (TEAC values of 1.21, 1.28, 1.26, 1.05, 1.69, 1.60, and 2.00 mM, respectively).

Senkyunolide H protects against MPP+-induced apoptosis via the ROS-mediated mitogen-activated protein kinase pathway in PC12 cells.

Senkyunolide H (SNH) is a phthalide isolated from the rhizome of Ligusticum chuanxiong Hort. that has been reported to have several pharmacological activities, including anti-atherosclerotic, antiproliferative, and cytoprotective effects. In this study, we investigated the neuroprotective effects and potential mechanisms of SNH against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress. We demonstrated that SNH pretreatment significantly attenuated MPP+-induced neurotoxicity and apoptosis in PC12 cells. In addition, SNH attenuated the effect of MPP+ on the expression of the pro-apoptotic factors Bax and caspase-3. Meanwhile, SNH prevented oxidative stress by reducing reactive oxygen species generation, mitochondrial membrane potential loss, cytochrome C release, and malondialdehyde levels while increasing antioxidant enzyme activity (e.g., superoxide dismutase, catalase, and glutathione peroxidase). In addition, SNH inhibited nuclear accumulation of nuclear factor-κB and c-Jun N-terminal kinase and phosphorylation p38 mitogen-activated protein kinases (MAPKs). Overall, this investigation provides novel evidence that SNH exerts neuroprotective effects via the ROS-mediated MAPK pathway and represents a potential preventive or therapeutic agent for neuronal disorders.

Phenylpropanoid glycosides from the leaves of Paulownia coreana.

Study on the water soluble fraction from the leaves of Paulownia coreana led to the isolation of verbascoside (1), isoverbascoside (2), campneoside II (3), and a new phenylpropanoid glycoside, (R,S)-7-hydroxy-7-(3,4-dihydroxyphenyl)-ethyl-O-alpha-L-rhamnopyranosyl(1 --> 3)-beta-d-(6-O-caffeoyl)-glucopyranoside (4). The structures of these compounds were established on the basis of spectroscopic evidence.

Purification of Four Flavonoid Glycosides from Lotus (Nelumbo nucifera Gaertn) plumule by Macroporous Resin Combined with HSCCC.

High-speed counter-current chromatography (HSCCC) combined with macroporous resin (MR) column was successfully applied to the isolation and purification of four flavonoid glycosides from the medicinal herb Lotus plumule (LP). A polar two-phase solvent system composed of ethyl acetate-n-butanol-water (1:2:3, v/v/v) was selected by high-performance liquid chromatography (HPLC) and run on a preparative scale where the lower aqueous phase was used as the mobile phase with a head-to-tail elution mode. Quercetin-3-O-ß-D-glucopyranoside (15 mg), isorhamnetin-3-O-ß-D-glucopyranoside (13 mg), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (18 mg) and apigenin 6,8-di-C-ß-D-glucopyranoside (48 mg) were obtained in a one-step HSCCC separation from 240 mg of the sample. The purity of each compound was over 95% as determined by HPLC. Chemical structures of the isolated compounds were identified by electrospray ionization mass spectrometry (ESI-MS-MS) and nuclear magnetic resonance (NMR) methods. Moreover, the four compounds were isolated from LP for the first time.

Simple and green fabrication of AgCl/Ag-cellulose paper with antibacterial and photocatalytic activity.

A green in situ technique to prepare a kind of multifunctional hybrid paper, AgCl/Ag particles hybrid cellulose-paper (AgCl/Ag-paper), was established. The AgCl/Ag-paper was obtained from a facile ultrasound agitation procedure. Scanning electron microscope observation showed that AgCl/Ag particles were highly dispersed outside surface and inside of the paper matrix. The resultant AgCl/Ag-paper demonstrated satisfactory antibacterial activity and biocompatibility. Moreover, AgCl/Ag-paper showed good photocatalytic activity and stability for decomposing organic pollutants (methyl blue) under the direct sunlight. Overall, this work provided a simple and green approach for the preparation of a new paper-based material with effectively antibacterial, photocatalytic activity, and biocompatibility for various applications and also showed the potential of scale-up production.

Fabrication of high-performance poly(l-lactic acid)/lignin-graft-poly(d-lactic acid) stereocomplex films.

The need for green renewable alternatives such as lignin to traditional fillers has driven recent interest in polylactic acid blend materials. Herein, lignin-graft-polylactic acid copolymers (LG-g-PDLA, LG-g-PDLLA, and LG-g-PLLA) have been synthesized via ring-opening polymerization of d-, dl-, and l-lactic acid. Then poly(l-lactic acid)/lignin-graft-polylactic acid (PLLA/LG-g-PDLA, /LG-g-PDLLA, and /LG-g-PLLA) complex films have been prepared. The results showed that, compared with LG-g-PDLA and LG-g-PLLA, a small amount of LG-g-PDLA addition could improve the crystallization rate, reduce the glass transition temperature and cold crystallization temperature of PLLA due to the stereocomplex crystallites. The thermal stability, tensile strength and strain of the stereocomplex films were also enhanced. Moreover, the PLLA/LG-g-PDLA films have good ultraviolet resistance and excellent biocompatibility. This study provides a green approach to design advanced polylactic acid-based blends with renewable natural resources.

Bioconversion of conjugated linoleic acid by Lactobacillus plantarum CGMCC8198 supplemented with Acer truncatum bunge seeds oil.

Conjugated linoleic acid (CLA) isomers, c9, t11-CLA and t10, c12-CLA, have been proved to exhibit excellent biomedical properties for potential use in anti-cancer applications and in reducing obesity. Acer truncatum Bunge (ATB), which is rich in unsaturated fatty acids, including oleic acid, linoleic acid, and nervonic acid, is a new resource for edible oil. In the present study, we developed a new method for producing two CLA isomers from ATB-seed oil by fermentation using Lactobacillus plantarum CGMCC8198 (LP8198), a novel probiotics strain. Polymerase chain reaction results showed that there was a conserved linoleate isomerase (LIase) gene in LP8198, and its transcription could be induced by ATB-seed oil. Analyses by gas chromatography-mass spectrometry showed that the concentration of c9, t11-CLA and t10, c12-CLA in ATB-seed oil could be increased by about 9- and 2.25-fold, respectively, after being fermented by LP8198.

Apigenin-7-O-ß-D-glucuronide inhibits LPS-induced inflammation through the inactivation of AP-1 and MAPK signaling pathways in RAW 264.7 macrophages and protects mice against endotoxin shock.

Apigenin-7-O-ß-D-glucuronide (AG), an active flavonoid derivative isolated from the agricultural residue of Juglans sigillata fruit husks, possesses multiple pharmacological activities, including anti-oxidant, anti-complement, and aldose reductase inhibitory activities. To date, no report has identified the anti-inflammatory mechanisms of AG. This study was therefore designed to characterize the molecular mechanisms of AG on lipopolysaccharide (LPS)-induced inflammatory cytokines in RAW 264.7 cells and on endotoxin-induced shock in mice. AG suppressed the release of nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without affecting cell viability. Additionally, AG suppressed LPS-induced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α. AG treatment decreased the translocation of c-Jun into the nucleus, and decreased activator protein-1 (AP-1)-mediated luciferase activity through the inhibition of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) phosphorylation. Consistent with the in vitro observations, AG protected mice from LPS-induced endotoxin shock by inhibiting proinflammatory cytokine production. Taken together, these results suggest that AG may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

A novel self-assembled targeted nanoparticle platform based on carboxymethylcellulose co-delivery of anticancer drugs.

Single-drug therapy for cancer is greatly hampered by its non-specific delivery to the target tissue, limited efficacies, poor tolerability, and resistance profiles. In order to overcome these limitations, we developed a new targeted nanoparticle platform for co-delivery of two different anticancer drugs. A conjugate based on carboxymethylcellulose (CMC) was first synthesized by introducing hydrophilic molecules (PEG), target molecules (folate), and drug molecules (betulinic acid) into CMC. Then another anticancer drug hydroxycamptothecine (HCPT) was encapsulated into the nanoparticles from the conjugate using a simple nanoprecipitation method. The obtained nanoparticles possessed appropriate size (∼180 nm), high drug loading efficiency (∼23 wt% BA, 21.15 wt% HCPT), a slow drug release rate, higher blood circulation half-time of free BA (6.4-fold) and HCPT (6.0-fold), and high synergetic activity of BA and HCPT toward cancer cells. Furthermore, the targeted nanoparticles showed rapid cellular uptake by tumor cells. The antitumor effect of the nanoparticles in a mouse tumor xenograft model exhibited a much better tumor inhibition efficacy and fewer side effects than that of BA and HCPT, strongly supporting their application as efficient carriers for anticancer therapy.

Self-assembled targeted folate-conjugated eight-arm-polyethylene glycol-betulinic acid nanoparticles for co-delivery of anticancer drugs.

In this study, a targeted nanoparticle platform for co-delivery of anticancer drugs based on folate-conjugated eight-arm-polyethylene glycol-betulinic acid (F-8arm-PEG-BA) was first presented. F-8arm-PEG-BA was synthesized by introducing target molecules (folate) and drug molecules (betulinic acid, BA) to hydrophilic molecules (8arm-PEG). Then another anticancer drug, hydroxycamptothecin (HCPT), was encapsulated into the self-assembled nanoparticles from the conjugate by a simple nanoprecipitation method. These F-8arm-PEG-BA/HCPT nanoparticles (NPs) had a small size (∼120 nm), acceptable critical aggregation concentration (∼64.8 µg mL-1), and high drug loading (∼18 wt% BA and ∼16 wt% HCPT). Compared to the free drugs, the nanoparticles significantly improved the cellular cytotoxicity and exhibited an obvious synergistic effect by the co-delivery of two different anticancer drugs, BA and HCPT. Pharmacokinetics study revealed the nanoparticles could prolong the circulation of BA and HCPT in the blood. In vivo studies indicated that the nanoparticles enhanced tumor targeting and antitumor activity with lower systemic toxicity. In conclusion, F-8arm-PEG-BA/HCPT NPs have great potential for targeted chemotherapy for cancer.

Antibacterial active compounds from Hypericum ascyron L. induce bacterial cell death through apoptosis pathway.

Hypericum ascyron L. has been used as a traditional medicine for the treatment of wounds, swelling, headache, nausea and abscesses in China for thousands of years. However, modern pharmacological studies are still necessary to provide a scientific basis to substantiate their traditional use. In this study, the mechanism underlying the antimicrobial effect of the antibacterial activity compounds from H. ascyron L. was investigated. Bioguided fractionation of the extract from H. ascyron L. afforded antibacterial activity fraction 8. The results of cup plate analysis and MTT assay showed that the MIC and MBC of fraction 8 is 5 mg/mL. Furthermore, using Annexin V-FITC/PI, TUNEL labeling and DNA gel electrophoresis, we found that cell death with apoptosis features similar to those in eucaryon could be induced in bacteria strains after exposure to the antibacterial activity compounds from H. ascyron L. at moderate concentration. In addition, we further found fraction 8 could disrupt the cell membrane potential indicate that fraction 8 exerts pro-apoptotic effects through a membrane-mediated apoptosis pathway. Finally, quercetin and kaempferol 3-O-ß-(2″-acetyl)-galactopyranoside, were identified from fraction 8 by means of Mass spectrometry and Nuclear magnetic resonance. To our best knowledge, this study is the first to show that Kaempferol 3-O-ß-(2″-acetyl)-galactopyranoside coupled with quercetin had significant antibacterial activity via apoptosis pathway, and it is also the first report that Kaempferol 3-O-ß-(2″-acetyl)-galactopyranoside was found in clusiacea. Our data might provide a rational base for the use of H. ascyron L. in clinical, and throw light on the development of novel antibacterial drugs.

The extract of Hypericum ascyron L. induces bacterial cell death through apoptosis pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum ascyron L. (H. ascyron L.) has been used as a traditional medicine for the treatment of wounds, swelling, headache, nausea, stomach ache, abscesses, dysentery and chronic bronchitis. Pharmacological studies are necessary to provide a scientific basis to substantiate their traditional use. In this study, antimicrobial effect and its mechanism of the H. ascyron L. extract was investigated. MATERIALS AND METHODS: Antimicrobial activity of the H. ascyron L. extract was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT). To confirm the antimicrobial mechanism of H. ascyron L. extract on bacterial cells, Annexin V/propidium iodide (PI) double staining, TUNEL, and DNA laddering analysis were performed. RESULTS: Antibacterial effects of the H. ascyron L. extract were tested on Enterobacter cloacae, Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus and Micrococcus luteus, and the results showed that the sensitive bacteria of H. ascyron L. extract mainly included E. coli, S. aureus and M. luteus, especially M. luteus. The MBC value of H. ascyron L. extract on M. luteus was equal to the MIC (20mg/mL). H. ascyron L. extract could induce cells death of M. luteus through apoptosis pathway. CONCLUSIONS: This study provides scientific support for some of the traditional uses and the pharmacological activities of H. ascyron L. Our data provide a rational base for the folkloric use of H. ascyron L.

Neuroprotective effects of macranthoin G from Eucommia ulmoides against hydrogen peroxide-induced apoptosis in PC12 cells via inhibiting NF-κB activation.

Oxidative stress-mediated cellular injury has been considered as a major cause of neurodegenerative diseases including Alzheimer and Parkinson diseases. The scavenging of reactive oxygen species (ROS) mediated by antioxidants may be a potential strategy for retarding the disease's progression. Macranthoin G (MCG), isolated from Eucommia ulmoides, is a derivative from chlorogenic acid methyl ester and caffeic acid. This study is aimed to investigate the protective role of MCG against the cytotoxicity induced by hydrogen peroxide (H2O2) and to elucidate potential protective mechanisms in rat pheochromocytoma (PC12) cells. The results showed that the treatment of PC12 cells with MCG prior to H2O2 exposure effectively increased the cell viability, and stabilized the mitochondria membrane potential (MMP); furthermore, it enhanced the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and the levels of intracellular glutathione (GSH); it also decreased the malondialdehyde (MDA) content, intracellular ROS, caspase-3 activation, as well as cell apoptosis. In addition, the MCG treatment minimized the cell injury by H2O2 via down-regulation of the NF-κB pathway as well as activation of phosphorylation of IκBα, p38, and the extracellular signal-regulated kinase (ERK). These results showed that that MCG is promising as a potential therapeutic agent for neurodegenerative diseases induced by oxidative damage and should be encouraged for further research.

Antioxidant properties and neuroprotective effects of isocampneoside II on hydrogen peroxide-induced oxidative injury in PC12 cells.

Oxidative stress has been considered as a major cause of cell damage in various neurodegenerative disorders. One of the reasonable strategies for delaying the disease's progression is to prevent reactive oxygen species (ROS) mediated cellular injury by dietary or pharmaceutical augmentation of free radical scavengers. Isocampneoside II (ICD) is an active phenylethanoid glycoside isolated from the medicinal hardwood genus Paulownia. This study was designed to explore free radical scavenging potential of ICD in different in vitro systems and its protective role in hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. The results showed ICD eliminated approximately 80.75% superoxide radical at the concentration of 0.1mg/ml and inhibited metal chelating by 22.07% at 8 mg/ml. Additionally, ICD showed a strong ability on reducing power and provided protection against oxidative protein damage induced by hydroxyl radicals. Pretreatment of PC12 cells with ICD prior to H2O2 exposure elevated cell viability, enhanced activity of superoxide dismutase and catalase, and decreased levels of malondialdehyde and intracellular ROS. Furthermore, ICD inhibited cell apoptosis and Bax/Bcl-2 ratio induced by H2O2. These findings suggested ICD may be considered as a potential antioxidant agent and should encourage for further research in neurodegenerative diseases.

Sulfated modification of the polysaccharide from Cordyceps_gunnii mycelia and its biological activities.

A chemically new sulfated polysaccharide (SPS50) was prepared from the water soluble polysaccharide (PS50), isolated from Cordyceps_gunnii mycelia, by concentrated sulfuric acid method. The yield of crude SPS50 was 62.34% and its specific rotation was [α](D)(20)=-36.75°. The structural characteristics of this chemically sulfated polysaccharide were determined based on the infrared analysis (IR), high performance liquid chromatography (HPLC) and sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE). Its biological properties including anti-oxidant and anti-tumor activities were also investigated. The results showed that the anti-oxidant capacity of SPS50 was not as good as SP50 and the anti-tumor activity of SPS50 was much better than PS50. SPS50 showed evident growth inhibition on K562 cells. The tumor inhibition ratio of SPS50 against K562 cells was 69.92%.