Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications.

Marine natural products comprise unique chemical structures and vast varieties of biological activities. This review aims to summarize halichondrin, a marine natural product, and its synthetic analogs along with its therapeutic properties and mechanisms. Halichondrin and its analogs, derived from marine sponges, exhibit potent antineoplastic properties, making them promising candidates for cancer therapeutics. These compounds, characterized by their complex molecular structures, have demonstrated significant efficacy in inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis in various cancer cell lines. Several types of halichondrins such as halichondrins B, C, norhalichondrin B, and homohalichondrin B have been discovered with similar anticancer and antitumor characteristics. Since naturally available halichondrins show hurdles in synthesis, recent advancements in synthetic methodologies have enabled the development of several halichondrin analogs, such as E7389 (eribulin), which have shown improved therapeutic indices. Eribulin has shown excellent immunomodulatory properties by several mechanisms such as reprogramming tumor microenvironments, facilitating the infiltration and activation of immune cells, and inhibiting microtubule dynamics. Despite promising results, challenges remain in the synthesis and clinical application of these compounds. This review explores the mechanisms underlying the immunomodulatory activity of halichondrin and its analogs in cancer therapy, along with their clinical applications and potential for future drug development.

Phosphorylation-dependent immunomodulatory properties of B.PAT polysaccharide isolated from Bifidobacterium animalis ssp. animalis CCDM 218.

A wide range of articles describe the role of different probiotics in the prevention or treatment of various diseases. However, currently, the focus is shifting from whole microorganisms to their easier-to-define components that can confer similar or stronger benefits on the host. Here, we aimed to describe polysaccharide B.PAT, which is a surface antigen isolated from Bifidobacterium animalis ssp. animalis CCDM 218 and to understand the relationship between its structure and function. For this reason, we determined its glycerol phosphate-substituted structure, which consists of glucose, galactose, and rhamnose residues creating the following repeating unit: To fully understand the role of glycerol phosphate substitution on the B.PAT function, we prepared the dephosphorylated counterpart (B.MAT) and tested their immunomodulatory properties. The results showed that the loss of glycerol phosphate increased the production of IL-6, IL-10, IL-12, and TNF-α in bone marrow dendritic cells alone and after treatment with Lacticaseibacillus rhamnosus GG. Further studies indicated that dephosphorylation can enhance B.PAT properties to suppress IL-1ß-induced inflammatory response in Caco-2 and HT-29 cells. Thus, we suggest that further investigation of B.PAT and B.MAT may reveal distinct functionalities that can be exploited in the treatment of various diseases and may constitute an alternative to probiotics.

Polysaccharides from Hericium erinaceus and its immunomodulatory effects on RAW 264.7 macrophages.

This study aimed to optimize the extraction of Hericium erinaceus polysaccharides (HEP) using ultrasound-assisted enzymatic extraction combined with Plackett-Burman design (PBD) and response surface methodology (RSM). The optimal extraction conditions were identified as: 33 min extraction time, 30:1 liquid to material ratio, 38 °C extraction temperature, 9 g/kg cellulase amount, pH 4, and 20 % ethanol concentration. Under these conditions, the extraction yield of HEP was 5.87 ± 0.16 %, consistent with the predicted results. Additionally, the potential immunomodulatory activity of HEP on RAW 264.7 macrophage was evaluated. The results revealed that HEP improved the immunostimulatory activity of RAW264.7 cells, evident from increased production of IL-6 and TNF-α. These findings suggest that HEP is capable of enhancing the immune activity of RAW 264.7 macrophage.

Structural characterization and immunomodulating assessment of ultra-purified water extracted fucoidans from Saccharina latissima, Alaria esculenta and Laminaria hyperborea.

Fucoidans, a group of high molecular weight polysaccharides derived mainly from brown algae, are characterized by their high fucose content, degree of sulfation (DS), and intra- and interspecific structural variation. Fucoidans are increasingly recognized due to various reported bioactivities, potentially beneficial for human health. To unlock their potential use within biomedical applications, a better understanding of their structure-functional relationship is needed. To achieve this, systematic bioactivity studies based on well-defined, pure fucoidans, and the establishment of standardized, satisfactory purification protocols are required. We performed a comprehensive compositional and structural characterization of crude and ultra-purified fucoidans from three kelps: Saccharina latissima (SL), Alaria esculenta (AE) and Laminaria hyperborea (LH). Further, the complement-inhibiting activity of the purified fucoidans was assessed in a human whole blood model. The purification process led to fucoidans with higher DS and fucose and lower concentrations of other monosaccharides. Fucoidans from SL and LH resembles homofucans, while AE is a heterofucan rich in galactose with comparably lower DS. Fucoidans from SL and LH showed complement-inhibiting activity in blood and blood plasma, while no inhibition was observed for AE under the same conditions. The results emphasize the importance of high DS and possibly fucose content for fucoidans' bioactive properties.

Immunomodulatory Effect of Cordyceps militaris Polysaccharide on RAW 264.7 Macrophages by Regulating MAPK Signaling Pathways.

Polysaccharide is one of the principal bioactive components found in medicinal mushrooms and has been proven to enhance host immunity. However, the possible mechanism of immunomodulatory activity of Cordyceps militaris polysaccharide is not fully understood. Hot water extraction and alcohol precipitation, DEAE-Sephadex A-25 chromatography, and Sephadex G-100 chromatography were used to isolate polysaccharide from C. militaris. A high-molecular-weight polysaccharide isolated from C. militaris was designated as HCMP, which had an Mw of 6.18 × 105 Da and was composed of arabinose, galactose, glucose, mannose, and xylose in a mole ratio of 2.00:8.01:72.54:15.98:1.02. The polysaccharide content of HCMP was 91.2% ± 0.16. The test in vitro showed that HCMP activated mouse macrophage RAW 264.7 cells by enhancing phagocytosis and NO production, and by regulating mRNA expressions of inflammation-related molecules in RAW 264.7 cells. Western blotting revealed that HCMP induced the phosphorylation of mitogen-activated protein kinases (MAPKs). Moreover, using inhibitors of MAPKs decreased the mRNA levels of inflammation-related molecules induced by HCMP. These data evidenced that the immunomodulatory effect of HCMP on RAW 264.7 macrophages was mediated via the MAPK signaling pathway. These findings suggested that HCMP could be developed as a potent immunomodulatory agent for use in functional foods and dietary supplements.

Immunomodulatory of sesquiterpenoids and sesquiterpenoid dimers-based toll-like receptor 4 (TLR4) from Dysoxylum parasiticum stem bark.

In recent decades, the interest in natural products with immunomodulatory properties has increased due to their therapeutic potential. These products have a wider range of pharmacological activities and demonstrate lower toxicity levels when compared to their synthetic counterparts. Therefore, this study aimed to investigate the immunomodulatory effects of sesquiterpenoids (SQs) and sesquiterpenoid dimers (SQDs) isolated from Dysoxylum parasiticum (Osbeck) Kosterm. stem bark on human and murine cells, particularly focusing on toll-like receptor 4 (TLR4). Utilizing the secreted alkaline phosphatase (SEAP) assay on engineered human and murine TLR4 of HEK-Blue cells, antagonist TLR4 compounds were identified, including SQs 6, 9, and 10, as well as SQDs 17 and 22. The results showed that 10-hydroxyl-15-oxo-α-cadinol (9) had a potent ability to reduce TLR4 activation induced by LPS stimulation, with minimal toxicity observed in both human and murine cells. The SEAP assay also revealed diverse immune regulatory effects for the same ligand. For instance, SQs 12, 14, and 16 transitioned from antagonism on human to murine TLR4. The SQs (4, 7, 11, and 15) and SQDs (18-20) offered partial antagonist effect exclusively on murine TLR4. Furthermore, these selected SQs and SQDs were assessed for their influence on the production of proinflammatory cytokines TNF-α, IL-1α, IL-1ß, and IL-6 of the NF-κB signaling pathway in human and murine macrophage cell lines, showing a dose-dependent manner. Additionally, a brief discussion on the structure-activity relationship was presented.

A polysaccharide PRCP from Rosa cymosa Tratt fruit: Structural characteristics and immunomodulatory effects via MAPK pathway modulation in vitro.

The Rosa cymosa Tratt, an herbal plant from the Rosaceae family, has historically been valued in China for its medicinal and edible properties. In this study, a novel polysaccharide from R. cymosa fruit, termed PRCP (purified R. cymosa polysaccharide), was isolated using water extraction, decolorization, deproteinization, and ion-exchange chromatography. The structural characteristics of PRCP were investigated using monosaccharide composition analysis, methylation, GPC, FTIR, CD, and NMR spectroscopy. The immunomodulatory effect and potential mechanism of PRCP were evaluated in vitro using a macrophage cell model. Results indicated that PRCP (37.28 kDa) is a highly branched polysaccharide (72.61 %) primarily composed of arabinogalactan, rhamnogalacturonan, and galactoglucan domains with 13 types of glycosidic linkage fragments. Furthermore, PRCP appears to modulate immunomodulatory effects by influencing the phosphorylation of P38 and JNK proteins in the MAPK pathway. Collectively, these findings highlight the potential of PRCP as a promising natural functional food ingredient for immunostimulation.

Extraction, purification, structural characteristics, bioactivity and potential applications of polysaccharides from Semen Coicis: A review.

Semen Coicis (S. Coicis) has been regarded as a valuable source of traditional herbal medicine in China for thousands of years. S. Coicis polysaccharides (SCPs) are one of the most important bioactive ingredients of S. Coicis, which have attracted worldwide attention, because of their great marketing potential and development prospects. Hot water extraction is currently the most commonly used method to isolate SCPs. The structural characteristics of SCPs have been extensively investigated through various advanced modern analytical techniques to dissect the structure-activity relationships. SCPs are mainly composed of diverse monosaccharides, from which Rha and Ara are the most prevalent glycosyl groups. In addition, the structures of SCPs are found to be closely related to their multiple biological activities, including antioxidant activity, immunomodulatory function, antitumor activity, hypoglycemic effect, intestinal microbiota regulatory activity, anti-inflammatory activity, among others. In view of this, this review aimed to provide systematic and current information on the isolation, structural characteristics, and bioactivities of SCPs to support their future applications as therapeutic agents and functional foods.

Ultrasonic-assisted extraction of a low molecular weight polysaccharide from Nostoc commune Vaucher and its structural characterization and immunomodulatory activity.

In the current study, a novel crude polysaccharide (cNCEP) was extracted from N. commune Vaucher utilizing ultrasonic-assisted extraction (UAE) with 60 % ethanol, employing response surface methodology. The optimal yield of cNCEP was determined to be 8.07 ± 0.08 mg/g, achieved through ultrasonic-assisted extraction under the conditions of a material-to-liquid ratio of 1:22, temperature of 56 °C, power of 570 W, and duration of 147 min. Subsequent purification of NCEP via Sephadex G75 resulted in a novel polysaccharide with a molecular weight of 20.466 kDa. NCEP exhibited significant scavenging activites against DPPH and hydroxyl radicals, as well as notable in vitro immunomodulatory properties. Furthermore, the mechanisms underlying the immunomodulatory effects of NCEP, involving enhancement of immunity, were investigated, revealing potential regulation of MAPK and TLR4-IRF7-NF-κB signaling pathways through RNA-Seq and Western blot analyses. These findings highlight the promising potential of NCEP as an organic immunomodulatory agent and functional food ingredient.

Structural properties of glucan from Russula griseocarnosa and its immunomodulatory activities mediated via T cell differentiation.

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.

Systematic Review of Chemical Compounds with Immunomodulatory Action Isolated from African Medicinal Plants.

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.

Isolation, structural characterization and immunomodulatory activity on RAW264.7 cells of a novel exopolysaccharide of Dictyophora rubrovalvata.

Fungal polysaccharides have been explored by many for both structural studies and biological activities, but few studies have been done on the extracellular polysaccharides of Dictyophora rubrovalvata, so a new exopolysaccharide was isolated from Dictyophora rubrovalvata and its structure and its immunological activity were investigated. The crude exopolysaccharide (EPS) was purified by DEAE52 cellulose and Sephadex G-200 to obtain a new acidic polysaccharide (DR-EPS). DR-EPS (2.66 × 103 kDa) was consisted mainly of mannose, glucose, galactose and glucuronic acid with a molar ratio of 1: 0.86: 0.20: 0.01. In addition, DR-EPS increased the phagocytic activity of RAW264.7 cells up to 2.67 times of the blank control group. DR-EPS improved intracellular nucleic acid and glycogen metabolism as observed by AO and PAS staining. DR-EPS(40 µg/mL) promoted NO production up to 30.66 µmol, enhanced acid phosphatase (ACP) and superoxide dismutase (SOD) activities, with activity maxima of 660 U/gprot and 96.27 U/mgprot, respectively, and DR-EPS (160 µg / mL) significantly increased the lysozyme content as 2.73 times of the control group. The good immunological activity of extracellular polysaccharides of Dictyophora rubrovalvata provides directions for the use of fermentation broths.

Structural Characterization of Polygonatum Cyrtonema Polysaccharide and Its Immunomodulatory Effects on Macrophages.

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.

Bioactive constituents from Tinospora cordifolia (willd.): Isolation, synthesis and their immunomodulatory activity.

Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.). Our study resulted in the isolation of new compound, 27-hydroxy octacosyl ferulate (1) along with eleven known compounds (2-12). The structures of the isolated compounds were characterized by combination of NMR (1D and 2D) and Mass spectroscopic methods. The hemisynthesis of compound 12 (ferulic acid) yielded (12a-12d and 12e-12 m) derivatives. Further, the isolated compounds and synthesized derivatives were assessed for their immunomodulatory potentials by evaluating their cytotoxicity and pro-inflammatory effects against macrophage cells (IL-6) and DC activation markers (CD 11c and 86). The biological results indicated that crude extract displayed potent immunomodulatory activity while isolated compounds and synthetic analogues showed moderate activity. Among the tested compounds, new compound (1), quercetin (10) and derivatives 12b, 12c found to be non-cytotoxic and displayed immunomodulatory potentials. Therefore, these compounds can be studied for autoimmunity and other immune suppressing conditions.

The structures of two polysaccharides from Lepidium meyenii and their immunomodulatory effects via activating NF-κB signaling pathway.

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.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Characterization and immunomodulatory effect of an alkali-extracted galactomannan from Morchella esculenta.

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.

Molecular Cloning, Expression and Macrophage Activation of an Immunoregulatory Protein from Cordyceps militaris.

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.

Advances in plant-derived natural products for antitumor immunotherapy.

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.

Extraction, structural characterization, and antioxidant and immunomodulatory activities of a polysaccharide from Notarchus leachii freeri eggs.

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.