Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 823
1.
Carbohydr Polym ; 339: 122214, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823900

The polysaccharide, RGP2, was isolated from Russula griseocarnosa and its immunostimulatory effects were confirmed in cyclophosphamide (CTX)-induced immunosuppressed mice. Following purification via chromatography, structural analysis revealed that RGP2 had a molecular weight of 11.82 kDa and consisted of glucose (Glc), galactose (Gal), mannose, glucuronic acid and glucosamine. Bond structure analysis and nuclear magnetic resonance characterization confirmed that the main chain of RGP2 was formed by →6)-ß-D-Glcp-(1→, →3)-ß-D-Glcp-(1→ and →6)-α-D-Galp-(1→, which was substituted at O-3 of →6)-ß-D-Glcp-(1→ by ß-D-Glcp-(1→. RGP2 was found to ameliorate pathological damage in the spleen and enhance immune cell activity in immunosuppressed mice. Based on combined multiomics analysis, RGP2 altered the abundance of immune-related microbiota (such as Lactobacillus, Faecalibacterium, and Bacteroides) in the gut and metabolites (uridine, leucine, and tryptophan) in the serum. Compared with immunosuppressed mice, RGP2 also restored the function of antigen-presenting cells, promoted the polarization of macrophages into the M1 phenotype, positively affected the differentiation of helper T cells, and inhibited regulatory T cell differentiation through the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, ultimately exerting an immune boosting function. Overall, our findings highlight therapeutic strategies to alleviate CTX-induced immunosuppression in a clinical setting.


Basidiomycota , Cell Differentiation , Glucans , Animals , Mice , Basidiomycota/chemistry , Glucans/chemistry , Glucans/pharmacology , Glucans/isolation & purification , Cell Differentiation/drug effects , T-Lymphocytes/drug effects , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Male , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Cyclophosphamide/pharmacology , Mice, Inbred BALB C , Gastrointestinal Microbiome/drug effects
2.
Molecules ; 29(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38731500

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.


Phytochemicals , Plants, Medicinal , Plants, Medicinal/chemistry , Phytochemicals/pharmacology , Phytochemicals/chemistry , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacology , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunomodulating Agents/isolation & purification , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Africa , Animals
3.
Molecules ; 29(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38731567

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-ß-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.


Macrophages , Phagocytosis , Polygonatum , Polysaccharides , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Polygonatum/chemistry , Mice , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Animals , Phagocytosis/drug effects , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , RAW 264.7 Cells , Cytokines/metabolism , Cell Proliferation/drug effects , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunomodulating Agents/isolation & purification , Molecular Weight
4.
Int J Biol Macromol ; 269(Pt 1): 131761, 2024 Jun.
Article En | MEDLINE | ID: mdl-38663705

Lepidium meyenii Walp., also known as the "Peruvian national treasure", is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii. The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6-α-D-Glc, while branches feature T-α-L-Ara, 1,5-α-L-Ara, and T-α-D-Glc attached to the O-6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6-ß-D-Gal, 1,3,6-ß-D-Gal with a few 1,3-ß-D-GlcpA-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3-ß-D-Gal, T-ß-D-Gal, T-α-L-Ara, 1,5-α-L-Ara, with trace amounts of 1,4-ß-D-Glc and T-ß-D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1ß, TNF-α, and IL-6 from RAW 264.7 cells at concentrations ranging from 50 µg/mL to 400 µg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB-α, p-IκB-α, p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.


Lepidium , NF-kappa B , Polysaccharides , Signal Transduction , Lepidium/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Mice , NF-kappa B/metabolism , Animals , Signal Transduction/drug effects , RAW 264.7 Cells , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Molecular Weight , Cytokines/metabolism
5.
Carbohydr Polym ; 278: 118960, 2022 Feb 15.
Article En | MEDLINE | ID: mdl-34973775

In our continuous exploration for bioactive polysaccharides, a novel polysaccharide FMP-2 was isolated and purified from the fruiting bodies of Morchella esculenta by alkali-assisted extraction. FMP-2 had an average molecular weight of 1.09 × 106 Da and contained mannose, glucuronic acid, glucose, galactose, and arabinose in a molar ratio of 4.10:0.22:1.00:5.75:0.44. The backbone of FMP-2 mainly consisted of 1,2-α-D-Galp, 1,6-α-D-Galp, and 1,4-α-D-Manp, with branches of 1,4,6-α-D-Manp and 1,2,6-α-D-Galp. FMP-2 can stimulate phagocytosis and promote the secretion of NO, ROS, and cytokines like IL-6, IL-1ß, and TNF-α in RAW264.7 cells ranging from 25 to 400 µg/mL. FMP-2 had great repairing effect on the immune injury of zebrafish induced by chloramphenicol. The phagocytosis ability of zebrafish macrophages and the proliferation of neutrophils can be greatly enhanced by polysaccharide FMP-2 with concentrations from 50 to 200 µg/mL. These findings suggest that FMP-2 might be used as a potential immunomodulator in the food and pharmaceutical industries.


Alkalies/chemistry , Ascomycota/chemistry , Fruiting Bodies, Fungal/chemistry , Fungal Polysaccharides/pharmacology , Galactose/analogs & derivatives , Immunologic Factors/pharmacology , Mannans/pharmacology , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/isolation & purification , Galactose/chemistry , Galactose/isolation & purification , Galactose/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mannans/chemistry , Mannans/isolation & purification , Mice , Neutrophils/drug effects , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , RAW 264.7 Cells , Zebrafish
6.
Molecules ; 26(23)2021 Nov 24.
Article En | MEDLINE | ID: mdl-34885688

Protein components of C. militaris have been reported to possess various biological activities. In our previous research, a Cordyceps militaris-derived immunoregulatory protein (CMIP) was naturally isolated and showed the activity of inhibiting the metastasis of breast cancer cells. This study aimed to obtain recombinant CMIP (rCMIP) using recombinant expression and elucidate its ability to activate macrophages. Recombinant CMIP showed one band at approximately 15 kDa or 30 kDa, or two bands at 15 kDa and 30 kDa, under different denaturation conditions of electrophoresis. The cell binding assay showed that rCMIP selectively binds to the surface of macrophages. After adhesion, it did not induce the apoptosis of RAW 264.7 cells, but promoted their proliferation. Moreover, rCMIP significantly induced the expression of M1 macrophage polarization-related molecules. The mean fluorescence intensity (MFI) of CD 86 was enhanced by 2.1-fold and 3.2-fold under 0.64 µM and 1.6 µM of rCMIP treatment, respectively. Cytokines typically expressed in M1 macrophages, such as TNF-α, iNOS, IL-6, CCL 4, CCL 5 and CXCL 10, were also considerably induced by rCMIP, while the expression of cytokines in typical M2 macrophages, like Arg-1, CCL17 and CCL22, were not changed or slightly decreased. Under rCMIP treatment, the release of NO was also appreciably induced. In the present study, we reported cloning, expression and functional characterization of rCMIP, which was naturally isolated from the fruiting body of C. militaris in our previous study. The data imply that rCMIP possesses immunomodulatory activity in macrophages.


Cordyceps/chemistry , Immunologic Factors/genetics , Macrophage Activation/drug effects , Recombinant Proteins/genetics , Animals , Apoptosis/drug effects , Cloning, Molecular , Cordyceps/genetics , Cytokines/genetics , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Humans , Immunologic Factors/immunology , Immunologic Factors/isolation & purification , Immunologic Factors/pharmacology , Macrophage Activation/immunology , Macrophages/drug effects , Macrophages/immunology , Mice , NF-kappa B/genetics , NF-kappa B/immunology , Nitric Oxide/genetics , Nitric Oxide/immunology , RAW 264.7 Cells , Recombinant Proteins/immunology , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
7.
Arch Pharm Res ; 44(11): 987-1011, 2021 Nov.
Article En | MEDLINE | ID: mdl-34751930

In recent years, immunotherapy has emerged as a novel antitumor strategy in addition to traditional surgery, radiotherapy and chemotherapy. It uniquely focuses on immune cells and immunomodulators in the tumor microenvironment and helps eliminate tumors at the root by rebuilding the immune system. Despite remarkable breakthroughs, cancer immunotherapy still faces many challenges: lack of predictable and prognostic biomarkers, adverse side effects, acquired treatment resistance, high costs, etc. Therefore, more efficacious and efficient, safer and cheaper antitumor immunomodulatory drugs have become an urgent requirement. For decades, plant-derived natural products obtained from land and sea have provided the most important source for the development of antitumor drugs. Currently, more attention is being paid to the discovery of potential cancer immunotherapy modulators from plant-derived natural products, such as polysaccharides, phenols, terpenoids, quinones and alkaloids. Some of these agents have outstanding advantages of multitargeting and low side effects and low cost compared to conventional immunotherapeutic agents. We intend to summarize the progress of comprehensive research on these plant-derived natural products and their derivatives and discuss their possible mechanisms in regulating the immune system and their efficacy as monotherapies or in combination with regular chemotherapeutic agents.


Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Immunologic Factors/pharmacology , Neoplasms/drug therapy , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Immunologic Factors/isolation & purification , Immunologic Factors/therapeutic use , Neoplasms/immunology , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology
8.
Int J Biol Macromol ; 192: 546-556, 2021 Dec 01.
Article En | MEDLINE | ID: mdl-34648800

We recently isolated a polysaccharide from Polygala tenuifolia Willd. (PTP) and reported that such a PTP could induce cell apoptosis with FAS/FAS-L-mediated death receptor pathway in human lung cancer cells. Herein, we indicate antitumor activity and immunoregulation of PTP for S180 sarcoma cells by in vitro and in vivo targeting. In vitro, S180 cells took on prominent characteristics of apoptosis under-treated with PTP in follow-up antitumor activity studies, including irregular shrinkage and fragmentation nuclear, apoptotic bodies formation, and reduction of mitochondrial membrane potential (MMP). Additionally, flow cytometry indicated that the number of normal cells (FITC-/PI-) gradually decreased from 98.08% to 16.31%, while the number of apoptotic cells (FITC+/PI- or FITC+/PI+) increased from 0.87% to 54.84%. The ratio of BAX and Bcl-2 increased, which promoted the release of Cytochrome C (CytC), and it further maximized the expression of activated-caspase-9/-3. Additionally, the PTP revised the immune organ indexes, the activities of NK cells and lymphocytes, and induced the secretion of IL-2 (7.34-16.17%), IFN-γ (14.34-20.85%) and TNF-α (12.32-22.58%) in vivo. Thus, PTP can induce cell apoptosis and activate the immunoregulation mechanism thereby exhibiting biological activity.


Antineoplastic Agents, Phytogenic/pharmacology , Immunologic Factors/pharmacology , Plant Extracts/pharmacology , Polygala/chemistry , Polysaccharides/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Biomarkers , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Female , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Immunophenotyping , Membrane Potential, Mitochondrial/drug effects , Mice , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Reactive Oxygen Species/metabolism , Xenograft Model Antitumor Assays
9.
Bioorg Chem ; 116: 105275, 2021 11.
Article En | MEDLINE | ID: mdl-34601298

The crude polysaccharides (NLCEP) were extracted from Notarchus leachii freeri eggs strings by the saltextractionmethod. The extraction conditions were optimized using the single-factorexperimentmethod and response surface method (RSM). The results showed that the maximum extraction yield of NLCEP was obtained under the following conditions: NaCl solution concentration of 2.96 %, raw material to liquid ratio of 1: 40 g/mL, extraction time of 2 h and extraction temperature of 69 °C. A new novel pure polysaccharide fraction named as NLCEPs-1 was fractionated from NLCEP by using DEAE-Cellulose 52 and Sephadex G-100. Its structure and immunomodulatory and antioxidant activities were analyzed. The results exhibited that the molecular weight of NLCEPs-1 was 31.4 kDa and it was composed of rhamnose, glucose, galactose, xylose and arabinose in the molar percentage of 11.128: 63.770: 5.439: 6.585: 13.077. The backbone of NLCEPs-1 was mainly consisted of â†’ )4-α-d-Glcp (1→, →6)-α-d-Glcp (1→, →1)-ß-d-Galp and ß-d-Galp-(1→. NLCEPs-1 exhibited the strong antioxidant activity in scavenging ability of various free radicals and immunomodulatory activity by the enhancement of the pinocytic capacity, nitric oxide (NO) and cytokines.


Antioxidants/pharmacology , Gastropoda/chemistry , Immunologic Factors/pharmacology , Polysaccharides/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/isolation & purification , Biphenyl Compounds/antagonists & inhibitors , Cell Survival/drug effects , Cells, Cultured , Cytokines/analysis , Cytokines/metabolism , Dose-Response Relationship, Drug , Eggs , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Mice , Molecular Structure , Nitric Oxide/analysis , Nitric Oxide/metabolism , Picrates/antagonists & inhibitors , Polysaccharides/chemistry , Polysaccharides/isolation & purification , RAW 264.7 Cells , Structure-Activity Relationship
10.
Biochim Biophys Acta Gen Subj ; 1865(11): 129974, 2021 11.
Article En | MEDLINE | ID: mdl-34343644

Background Since December 2019, the newly emerged SARS-CoV-2 virus continues to infect humans and many people died from severe Covid-19 during the last 2 years worldwide. Different approaches are being used for treatment of this infection and its consequences, but limited results have been achieved and new therapeutics are still needed. One of the most interesting biotherapeutics in this era are Nanobodies which have shown very promising results in recent researches. Scope of review Here, we have reviewed the potentials of Nanobodies in Covid-19 treatment. We have also discussed the properties of these biotherapeutics that make them very suitable for pulmonary drug delivery, which seems to be very important route of administration in this disease. Major conclusion Nanobodies with their special biological and biophysical characteristics and their resistance against harsh manufacturing condition, can be considered as promising, targeted biotherapeutics which can be administered by pulmonary delivery pharmaceutical systems against Covid-19. General significance Covid-19 has become a global problem during the last two years and with emerging mutant strains, prophylactic and therapeutic approaches are still highly needed. Nanobodies with their specific properties can be considered as valuable and promising candidates in Covid-19 therapy.


Antibodies, Neutralizing/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Immunologic Factors/therapeutic use , SARS-CoV-2/drug effects , Single-Domain Antibodies/therapeutic use , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/isolation & purification , Antiviral Agents/isolation & purification , Antiviral Agents/metabolism , COVID-19/immunology , COVID-19/virology , Camelus , Drug Delivery Systems , Humans , Immune Sera/chemistry , Immunologic Factors/biosynthesis , Immunologic Factors/isolation & purification , Lung/drug effects , Lung/immunology , Lung/virology , Molecular Targeted Therapy/methods , Peptide Library , Protein Binding/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Single-Domain Antibodies/biosynthesis , Single-Domain Antibodies/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
11.
Carbohydr Polym ; 269: 118288, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-34294314

A pectic polysaccharide (named CMDP-4b) with a molecular weight of 31.97 kDa was extracted from Cucurbita moschata Duch and purified by column chromatography. On the basis of methylation, Fourier-transform infrared, monosaccharide composition, and one- and two-dimensional nuclear magnetic resonance spectroscopy analyses, the structure of CMDP-4b was determined to be composed of an α-1,4-linked homogalacturonan backbone, which was slightly acetylated and highly methyl-esterified, and branched at the O-3 position of the →4)-α-D-GalpA-6-OMe-(1→. Immunomodulatory assays showed that CMDP-4b not only induced the secretion of nitrous oxide and cytokines (i.e. IL-1ß, TNF-α, and IL-6) but also promoted pinocytic and phagocytic activities of macrophages, suggesting that CMDP-4b possessed immunomodulatory activity. Moreover, toll-like receptor 4 and complement receptor 3 may play a critical role in CMDP-4b-induced macrophage activation through the NF-κB and the MAPKs signaling pathways. Our study provides the molecular basis for the potential use of CMDP-4b as a natural immunostimulant.


Cucurbita/chemistry , Immunologic Factors/pharmacology , Pectins/pharmacology , Animals , Cell Survival/drug effects , Cytokines/metabolism , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Macrophages/drug effects , Macrophages/metabolism , Mice , Nitric Oxide/metabolism , Pectins/chemistry , Pectins/isolation & purification , Phagocytosis/drug effects , Pinocytosis/drug effects , RAW 264.7 Cells , Signal Transduction/drug effects
12.
Carbohydr Polym ; 269: 118331, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-34294341

This study aimed to extract polysaccharides from citron and analyze their structures and potential bioactivities. Two novel polysaccharides CM-1 and CM-2 were purified from citron by DEAE-Sepharose Fast Flow and Sephadex G-100 column chromatography. Monosaccharide composition, linkage and NMR data were used to infer their sugar chains composition. The anti-breast cancer cells and immunoregulatory activities of CM-1 and CM-2 were investigated. Results indicated that CM-1 (Mw = 21,520 Da), composed of arabinose, xylose, mannose and glucose in a molar ratio of 10.78:11.53:1.00:1.70, was arabinoxylan (AX) with (1 â†’ 4)-linked ß-d-Xylp skeleton monosubstituted with α-l-Araf units at O-3 position. While CM-2 (Mw = 22,303 Da), composed of arabinose, mannose, glucose and galactose in a molar ratio of 25.46:1.45:1.00:6.57, was galactoarabinan (GA) with (1 â†’ 5)-linked α-l-Araf backbone substituted by ß-d-Galp units at O-2 and/or O-3 positions. Both polysaccharides exhibited potential inhibiting cancer and immunostimulatory activities in vitro, especially CM-1. These results provide a basis for further research on citron polysaccharides.


Antineoplastic Agents/pharmacology , Citrus/chemistry , Galactans/pharmacology , Immunologic Factors/pharmacology , Xylans/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/toxicity , Carbohydrate Sequence , Cell Line, Tumor , Cell Proliferation/drug effects , Galactans/chemistry , Galactans/isolation & purification , Galactans/toxicity , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Immunologic Factors/toxicity , Interleukin-6/metabolism , Mice , Molecular Weight , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/metabolism , Xylans/chemistry , Xylans/isolation & purification , Xylans/toxicity
13.
Carbohydr Polym ; 269: 118343, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-34294350

Cordyceps is one of the most expensive and widely used functional foods. But the authenticity is still a concern due to the lack of appropriate markers. By targeting polysaccharides, this study aimed to develop a specific, and bioactive marker for Cordyceps. Firstly, the results of screening tests of 250 samples by examining both genetic markers and polysaccharide profile showed that a unique polysaccharide fraction (named CCP) was particular to the caterpillar parts. Its potential as a marker was further demonstrated by its ability to induce NO and cytokine production in RAW 264.7 cells. CCP was characterized to be an α-1,4-glucan with a branch at C-6 by the conventional structure analyzing and de novo oligosaccharides sequencing. The content of CCP was closely correlated to the traditional classification criteria. Generally, CCP was a marker that simultaneously enables qualitative and quantitative analysis of Cordyceps.


Cordyceps/chemistry , Glucans/pharmacology , Immunologic Factors/pharmacology , Moths/chemistry , Animals , Biomarkers/chemistry , Carbohydrate Sequence , Cell Survival/drug effects , Food Contamination/prevention & control , Glucans/chemistry , Glucans/isolation & purification , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Mice , Nitric Oxide/metabolism , RAW 264.7 Cells
14.
Molecules ; 26(12)2021 Jun 15.
Article En | MEDLINE | ID: mdl-34203809

Rhododendron (Ericaceae) extracts contain flavonoids, chromones, terpenoids, steroids, and essential oils and are used in traditional ethnobotanical medicine. However, little is known about the immunomodulatory activity of essential oils isolated from these plants. Thus, we isolated essential oils from the flowers and leaves of R. albiflorum (cascade azalea) and analyzed their chemical composition and innate immunomodulatory activity. Compositional analysis of flower (REOFl) versus leaf (REOLv) essential oils revealed significant differences. REOFl was comprised mainly of monoterpenes (92%), whereas sesquiterpenes were found in relatively low amounts. In contrast, REOLv was primarily composed of sesquiterpenes (90.9%), with a small number of monoterpenes. REOLv and its primary sesquiterpenes (viridiflorol, spathulenol, curzerene, and germacrone) induced intracellular Ca2+ mobilization in human neutrophils, C20 microglial cells, and HL60 cells transfected with N-formyl peptide receptor 1 (FPR1) or FPR2. On the other hand, pretreatment with these essential oils or component compounds inhibited agonist-induced Ca2+ mobilization and chemotaxis in human neutrophils and agonist-induced Ca2+ mobilization in microglial cells and FPR-transfected HL60 cells, indicating that the direct effect of these compounds on [Ca2+]i desensitized the cells to subsequent agonist activation. Reverse pharmacophore mapping suggested several potential kinase targets for these compounds; however, these targets were not supported by kinase binding assays. Our results provide a cellular and molecular basis to explain at least part of the beneficial immunotherapeutic properties of the R. albiflorum essential oils and suggest that essential oils from leaves of this plant may be effective in modulating some innate immune responses, possibly by inhibition of neutrophil migration.


Oils, Volatile/chemistry , Rhododendron/chemistry , Flowers/chemistry , HL-60 Cells , Humans , Immunologic Factors/isolation & purification , Immunologic Factors/metabolism , Immunomodulation/drug effects , Monoterpenes/pharmacology , Neutrophils/drug effects , Oils, Volatile/pharmacology , Plant Leaves/chemistry , Receptors, Formyl Peptide/drug effects , Receptors, Formyl Peptide/metabolism , Rhododendron/metabolism , Sesquiterpenes/pharmacology
15.
J Ethnopharmacol ; 277: 114256, 2021 Sep 15.
Article En | MEDLINE | ID: mdl-34062250

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal polysaccharides have exhibited great immune-enhancing potential. Adjuvants are a key tool for developing efficacious vaccines. In our previous study, a water-soluble polysaccharide extracted from wild Cistanche deserticola Y.C. Ma showed potent immunostimulatory activity. AIM OF STUDY: In this study, the immune profiles and efficacy of aqueous extracts of cultivated Cistanche deserticola Y.C. Ma (AECCD) on ICR mice against ovalbumin (OVA) were investigated. In vitro experiments, the possible DC activation mechanism by AECCD was evaluated. MATERIALS AND METHODS: AECCD were extracted using hot water after which the crude polysaccharides were precipitated by ethanol. Mice were firstly immunized subcutaneously with OVA (10 µg per mouse) alone or OVA (10 µg per mouse) respectively containing different dose of AECCD (200, 400 and 800 µg per mouse) on Days 1 and 14 and the magnitude and kinetics of antibodies and cell-mediated responses were then assessed. RESULTS: AECCD elicited vigorous and long-term IgG responses with mixed Th1/Th2 responses and up-regulated levels of Th-associated cytokines (CD4+IL-4, CD4+IFN-γ and CD8+IFN-γ). Moreover, AECCD induced the strong cellular immune response characterized by increased splenocyte proliferation as well as the activated T cell response. Notably, AECCD significantly enhanced the maturation of dendritic cells (DCs) and inhibited Tregs. In vitro experiments, Preliminary tests indicated that AECCD induced DC activation by promoting phenotypic maturation, cytokine section and allostimulatory activity. Toll-like receptor 4 (TLR4) was an essential receptor for DCs to directly bind AECCD. The inhibitors of NF-κB decreased the expression levels of CD40, CD80, CD86 and MHC-II and the production of IFN-γ, TNF-α and IL-6 through DCs. CONCLUSIONS: Finally, these findings suggested that AECCD could elicit potent and durable antigen specific immune responses through DC activation, which was involved in the regulation of maturation markers and cytokine expression via TLR4-related NF-κB pathway. The study indicates that AECCD is a potential immunomodulator.


Adjuvants, Immunologic/pharmacology , Cistanche/chemistry , Plant Extracts/pharmacology , Polysaccharides/pharmacology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/isolation & purification , Animals , Cytokines/immunology , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dose-Response Relationship, Drug , Female , Immunologic Factors/administration & dosage , Immunologic Factors/isolation & purification , Immunologic Factors/pharmacology , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Ovalbumin , Plant Extracts/administration & dosage , Polysaccharides/administration & dosage , Polysaccharides/isolation & purification
16.
Int J Biol Macromol ; 186: 433-444, 2021 Sep 01.
Article En | MEDLINE | ID: mdl-34171261

Bifidocin LHA, a novel bacteriocin, was extracted from bee honey B. adolescentis and purified. Bifidocin LHA was characterized as a protein in nature, without lipid or carbohydrate moieties, the molecular weight was 16,000 Da protein, heat-stable and active at a wide range of pH values, bactericidal effect, detergent, and solvents did not affect bifidocin activity and can be classified as type II bacteriocin. In vitro, the antibacterial activity of purified bifidocin LHA was significantly higher than crude bifidocin LHA (P < 0.05) against Pseudomonas aeruginosa (P. aeruginosa). The antibiofilm activity of bifidocin LHA was significantly higher than the antibiofilm activity of Amikacin (P < 0.05). In vivo, bifidocin LHA demonstrates a significant decreased in the number of P. aeruginosa in the eye, while complete clearance of P. aeruginosa comparing with the control (P < 0.05) when treating with Bifidobacterium adolescentis and bifidocin LHA together. Bifidobacterium adolescentis and bifidocin LHA treatment together induced substantial elevation of IL10 and IL-12 concentrations (P < 0.01) that helped to prevent damage caused by the inflammatory response. Succeeded to eradicate P. aeruginosa infection improved by histological patterns of the eye tissues. This study indicated Bifidobacterium adolescentis and bifidocin LHA consider as crucial strategies for the practical treatment of eye infection in the future.


Anti-Bacterial Agents/pharmacology , Bacteriocins/pharmacology , Biofilms/drug effects , Eye Infections, Bacterial/drug therapy , Immunologic Factors/pharmacology , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Animals , Anti-Bacterial Agents/isolation & purification , Bacteriocins/isolation & purification , Bees/microbiology , Bifidobacterium adolescentis/chemistry , Biofilms/growth & development , Cytokines/metabolism , Disease Models, Animal , Eye Infections, Bacterial/immunology , Eye Infections, Bacterial/microbiology , Immunologic Factors/isolation & purification , Inflammation Mediators/metabolism , Male , Mice, Inbred BALB C , Microbial Sensitivity Tests , Pseudomonas Infections/immunology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/growth & development
17.
Chem Pharm Bull (Tokyo) ; 69(5): 421-431, 2021.
Article En | MEDLINE | ID: mdl-33952852

Rosa laevigata Michx., a medicinal and edible plant in China, has exerted a variety of medicinal values and health benefits. This present review aims to achieve a comprehensive and up-to-date investigation in the phytochemistry and pharmacology of R. laevigata. According to these findings in the literature, approximately 123 chemical ingredients covering triterpenoids, flavonoids, tannis, lignans and polysaccharides, have been characterized from various parts of this species. Among these isolates, 77 triterpenoids have been isolated and thus regarded as the primary and characteristic substance. Based on the chemical structures, most of the obtained triterpenoids can be classified into polyhydroxy triterpenoids and readily divided into four categories: ursane-type, oleanane-type, lupinane-type, as well as seco-triterpenoids. The crude extracts and the purified compounds have demonstrated various pharmacological effects in vitro and in vivo, such as antioxidant activity, immunomodulatory effect, anti-inflammatory effect, liver protection, kidney protection, cardiovascular protection, neuroprotective effect and improvement of diabetic cataract. Noticeably, these pharmacological results of R. laevigata provide evidences for its traditional uses. In addition, these different chemical ingredients existing in the title plant may have synergistic effects. In conclusion, the chemical profiles, including ingredients and structures, together with the modern pharmacological properties have been adequately summarized. These evidences have revealed this plant to be a valuable source for therapeutic foodstuff and more attention should be paid to a better utilization of this plant.


Phytochemicals/pharmacology , Plants, Edible/chemistry , Plants, Medicinal/chemistry , Rosa/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/pharmacology , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Immunologic Factors/pharmacology , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Protective Agents/chemistry , Protective Agents/isolation & purification , Protective Agents/pharmacology
18.
Front Immunol ; 12: 670279, 2021.
Article En | MEDLINE | ID: mdl-34054843

The inclusion of a medicinal plant leaf extract (MPLE) from sage (Salvia officinalis) and lemon verbena (Lippia citriodora), rich in verbascoside and triterpenic compounds like ursolic acid, was evaluated in gilthead seabream (Sparus aurata) fed a low fishmeal-based diet (48% crude protein, 17% crude fat, 21.7 MJ kg-1, 7% fishmeal, 15% fish oil) for 92 days. In particular, the study focused on the effect of these phytogenic compounds on the gut condition by analyzing the transcriptomic profiling (microarray analysis) and histological structure of the intestinal mucosa, as well as the histochemical properties of mucins stored in goblet cells. A total number of 506 differentially expressed genes (285 up- and 221 down-regulated) were found when comparing the transcriptomic profiling of the intestine from fish fed the control and MPLE diets. The gut transcripteractome revealed an expression profile that favored biological mechanisms associated to the 1) immune system, particularly involving T cell activation and differentiation, 2) gut integrity (i.e., adherens and tight junctions) and cellular proliferation, and 3) cellular proteolytic pathways. The histological analysis showed that the MPLE dietary supplementation promoted an increase in the number of intestinal goblet cells and modified the composition of mucins' glycoproteins stored in goblet cells, with an increase in the staining intensity of neutral mucins, as well as in mucins rich in carboxylated and weakly sulfated glycoconjugates, particularly those rich in sialic acid residues. The integration of transcriptomic and histological results showed that the evaluated MPLE from sage and lemon verbena is responsible for the maintenance of intestinal health, supporting gut homeostasis and increasing the integrity of the intestinal epithelium, which suggests that this phytogenic may be considered as a promising sustainable functional additive for aquafeeds.


Immunity, Mucosal/drug effects , Immunologic Factors/pharmacology , Intercellular Junctions/drug effects , Intestinal Mucosa/drug effects , Plant Extracts/pharmacology , Salvia officinalis , Sea Bream , T-Lymphocytes/drug effects , Verbenaceae , Adherens Junctions/drug effects , Adherens Junctions/metabolism , Animals , Cell Differentiation/drug effects , Goblet Cells/drug effects , Goblet Cells/immunology , Goblet Cells/metabolism , Immunologic Factors/isolation & purification , Intercellular Junctions/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Lymphocyte Activation/drug effects , Mucins/metabolism , Permeability/drug effects , Plant Extracts/isolation & purification , Plant Leaves , Salvia officinalis/chemistry , Sea Bream/genetics , Sea Bream/immunology , Sea Bream/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tight Junctions/drug effects , Tight Junctions/metabolism , Transcriptome , Verbenaceae/chemistry
19.
Carbohydr Polym ; 266: 118106, 2021 Aug 15.
Article En | MEDLINE | ID: mdl-34044924

Longan (Dimocarpus longan Lour.) is a seasonal tropical fruit used by Chinese medicine in both fresh and dried pulp forms. Their polysaccharides have been reported to have biological activity. However, their composition and immune activity have not yet been disclosed. To fulfil this aim, hot water-soluble polysaccharides of fresh and dried longan pulp were fractionated according to their molecular weight by ultrafiltration (10, 50, 100 kDa cut off). The main polysaccharides recovered were 1,6-linked glucans branched at O-3 (4-8%), O-2 (1%), O-2,4 (0.1%), and O-3,4 (0.1%). The drying process promotes the solubility of the polysaccharides. These glucans from fresh and dried longan pulp have immunomodulatory activity, shown by in vitro phagocytosis, NO, TNF-α, and IL-6 macrophages production assays. They showed also to inhibit the inflammatory response induced by LPS. The immunological activity of these glucans seems to have different responses dependent on their molecular weight, related to the immune regulatory pathways.


Glucans/pharmacology , Immunologic Factors/pharmacology , Immunomodulation/drug effects , Sapindaceae/chemistry , Animals , Fruit/chemistry , Glucans/chemistry , Glucans/isolation & purification , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Molecular Structure , Nitric Oxide/metabolism , Phagocytosis/drug effects , RAW 264.7 Cells , Solubility , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism , Water/chemistry
20.
Carbohydr Polym ; 266: 118134, 2021 Aug 15.
Article En | MEDLINE | ID: mdl-34044950

Microwave-assisted extraction (MAE) is an emerging technology to obtain polysaccharides with an extensive spectrum of biological characteristics. In this study, the hypoglycemic, hypolipidemic, prebiotic, and immunomodulatory (e.g., antiinflammatory, anticoagulant, and phagocytic) effects of algal- and plant-derived polysaccharides rich in glucose, galactose, and mannose using MAE were comprehensively discussed. The in vitro and in vivo results showed that these bioactive macromolecules with the low digestibility rate could effectively alleviate the fatty acid-induced lipotoxicity, acute hemolysis, and dyslipidemia status. The optimally extracted glucomannan- and glucogalactan-containing polysaccharides revealed significant antidiabetic effects through inhibiting α-amylase and α-glucosidase, improving dynamic insulin sensitivity and secretion, and promoting pancreatic ß-cell proliferation. These bioactive macromolecules as prebiotics not only improve the digestibility in gastrointestinal tract but also reduce the survival rate of pathogens and tumor cells by activating macrophages and producing pro-inflammatory biomarkers and cytokines. They can effectively prevent gastrointestinal disorders and microbial infections without any toxicity.


Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Immunologic Factors/pharmacology , Polysaccharides/pharmacology , Prebiotics , Animals , Cell Line, Tumor , Chemical Fractionation/methods , Chlorophyta/chemistry , Cytokines/metabolism , Fungi/chemistry , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/toxicity , Hypolipidemic Agents/isolation & purification , Hypolipidemic Agents/toxicity , Immunologic Factors/isolation & purification , Immunologic Factors/toxicity , Microwaves , Nitric Oxide/metabolism , Phaeophyceae/chemistry , Phagocytosis/drug effects , Plants/chemistry , Polysaccharides/isolation & purification , Polysaccharides/toxicity
...