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Pateamines act as inhibitors of the RNA helicase eIF4A and exhibit antiviral and anticancer properties. Recently, we observed that inhibition of eIF4A by rocaglates affects the immune response. To investigate whether the observed immunomodulatory effects are specific to rocaglates or the inhibition of eIF4A, a comprehensive study was conducted on the influence of pateamines that exhibit the same inhibitory mode of action as rocaglates on various immune cells. The effects of pateamine A (PatA) and des-methyl des-amino pateamine A (DMDA) on the expression of surface markers, release of cytokines, cell proliferation, inflammatory mediators and metabolic activity in primary human monocyte-derived macrophages (MdM), T cells and B cells were assessed. Additionally, safety and bioavailability profiles were determined. DMDA revealed almost no immunomodulatory effects within the tested concentration range of 0.5-5 nM. PatA reduced B cell activation, as shown by reduced immune globulin release and decreased chemokine release from macrophages, while T cell function remained unaffected. Both DMDA and PatA showed low permeability in Caco-2 and Calu-3 cell barrier assays and no mutagenic potential. However, 10 nM PatA exhibited genotoxic potential, as shown by the micronucleus assay. In conclusion, DMDA had a good safety profile but exhibited low permeability, whereas PatA had a poor safety profile and also low permeability. The observed immunomodulatory effects of elF4A inhibitors on B cells appear to be target-specific.

Macrophages undergo activation in response to multiple stimuli, including pathogens, growth factors and natural products. The inflammatory response and oxidative stress play critical roles in such macrophage activation. Some natural products reportedly promote immunoregulatory effects and the control of macrophage activation. Caryocar villosum (Cv), a native amazon plant, contains compounds that are an important source of molecules capable of macrophage activation. Herein, we demonstrate the immunomodulatory effects of oil obtained from Caryocar villosum (CvO) on macrophages. Macrophages were treated with varying concentrations of CvO, and resulting cellular morphological and functional changes were evaluated, including the production of nitric oxide (NO), reactive oxygen species (ROS), cytokines and phagocytic activity. Treatment of cells with 50 and 100 μg/mL CvO induced morphological and physiological alterations in the macrophages, such as increased cell surface and phagocytic activity. Additionally, treatment increased the productions of inflammatory cytokines (INF-γ, TNF-α, IL-6) and anti-inflammatory cytokines (IL-17 and IL-10) by macrophages, and significantly decreased ROS levels. In conclusion, these data suggest that, due to molecular diversity, CvO promoted an immunomodulatory effect on macrophages, mediated by an increased production of cytokines, and inhibition of ROS generation and phagocytic activity. Thus, CvO presents potential as a therapeutic agent for the treatment of inflammatory and non-inflammatory diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Edilene Oliveira da Silva reports financial support was provided by National Council for Scientific and Technological Development. Jose Luiz M Nascimento reports financial support was provided by Fundação de Amparo à Pesquisa no Estado do Pará. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Saussurea laniceps is a traditional medicinal herb. In our previous study, a pectin polysaccharide, SLP-4, was isolated from the petals of S. laniceps. In this study, the immunomodulatory activity of SLP-4 was studied by analyzing its effects on macrophage (RAW 264.7 cells) polarization. The immunomodulatory activity assays indicated that SLP-4 could significantly enhance the pinocytic and phagocytic capacity and promote the expression and secretion of cytotoxic molecules (nitric oxide, increased by 6.4 times when the SLP-4 concentration was 800 μg/mL) and cytokines (tumor necrosis factor-α and interleukin-6 increased by 7.7 and 11.9 times, respectively) in original macrophage. The possible mechanism could be attributed to the activation of the mitogen-activated protein kinase and nuclear factor-κB signaling pathways through Toll-like receptors 2 and 4. Moreover, SLP-4 significantly induced M1 polarization of original macrophages and transferred macrophages from M2 to M1, but had little effect on the conversion of M1 macrophages into M2 phenotype. Overall, these results demonstrate the potential of SLP-4 as an attractive immunomodulating functional supplement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For background, Hirsutella sinensis , the only anamorphic fungus considered an effective substitute for Cordyceps sinensis , possesses immunoregulatory properties. However, the specific mechanism underlying the immunoregulatory function of Hirsutella sinensis remains unclear. The purpose is to investigate the therapeutic effects of Hirsutella sinensis alcohol extract (HSAE) on immune dysregulation and elucidate the underlying mechanisms involved. For methods, we established inflammatory and immunosuppression models in vitro and in vivo to evaluate the bidirectional immunoregulatory function of HSAE via qRT-PCR and immunoblotting. We also studied its potential mechanism via RNA sequencing and transcriptional analysis. We further established M1 and M2 cell models to explore the effect of HSAE on M1/M2 polarization using qRT-PCR, immunoblotting, and flow cytometry. For results, our data demonstrated enhanced proliferation, phagocytosis, and antipathogenic activities of macrophages. Treatment with HSAE led to increases in the proportions of CD3 + and CD4 + immune cells in cyclophosphamide-induced immunosuppressed mice. Additionally, HSAE reduced the lipopolysaccharide (LPS)-induced expression of Il1b , Il6 , Ifnb1 , and Cxcl10 by inhibiting the activation of the NF-κB and MAPK pathways in vitro and improved mouse survival by reducing the proportion of M1/M2 macrophages in septic mice. Finally, we found that HSAE inhibited M1 polarization by decreasing the expression of iNOS and CD86 and promoted M2 polarization by increasing the expression of ARG1 and CD206. For conclusions, our study provides evidence that HSAE has the potential to enhance immune responses and suppress excessive inflammation. These effects were realized by modulating macrophage polarization, providing novel insights into the fundamental mechanism underlying the bidirectional immunomodulatory effect of HSAE.

Aims: Fungi-derived exosome-like nanovesicles (ENs) are emerging as a highly promising class of nanoparticles, particularly noted for their cost-effective production. However, their impact on immune regulation and their potential as anti-tumor agents need further exploration. Our study specifically focused on the investigation of the immunomodulatory and anti-tumor properties of ENs derived from Cordyceps militaris, an edible fungus that had achieved large-scale commercial production, referred to as CMDENs., Main Methods: The ENs of C. militaris were collected through ultra-high-speed centrifugation, followed by characterization of their physicochemical properties and contents. Subsequently, the biological distribution of these vesicles was investigated using in vivo fluorescence imaging experiments. Finally, the immune activation and polarization of macrophages were examined through both in vitro and in vivo experiments., Key Findings: Herein, we presented the discovery of CMDENs that were rich in proteins, lipids, flavonoids and alkaloids. Immunomodulatory experiments conducted in vivo demonstrated that CMDENs exhibited protective effects against cyclophosphamide-induced immunosuppression in mice by significantly enhancing macrophage phagocytosis and peripheral blood immune cell counts. Moreover, CMDENs effectively induced the polarization of M0- and M2-like macrophages toward M1-like phenotype by activating MAPKs signaling pathway. Notably, CMDENs exhibited remarkable capabilities in inhibiting tumor growth by reprogramming tumor-associated macrophages and activating tumor-infiltrating T lymphocytes, without any observed toxicity in mice bearing tumors., Significance: Our research suggested that CMDENs possessed the potential to be explored as a nano-immunomodulatory agent for cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diabetic retinopathy (DR) stands as a prevalent secondary complication of diabetes, notably Type 1 Diabetes Mellitus (T1D), characterized by immune system involvement potentially impacting the retinal immune response mediated by microglia. Early stages of DR witness blood-retinal barrier permeabilization, facilitating peripheral immune cell interaction with the retinal immune system. Kaempferol (Kae), known for its potent anti-inflammatory activity, presents a promising avenue in DR treatment by targeting the immune mechanisms underlying its onset and progression. Our investigation delves into the molecular intricacies of innate immune cell interaction during DR progression and the attenuation of inflammatory processes pivotal to its pathology., Methods: Employing in vitro studies, we exposed HAPI microglial and J774.A1 macrophage cells to pro-inflammatory stimuli in the presence or absence of Kae. Ex vivo and in vivo experiments utilized BB rats, a T1D animal model. Retinal explants from BB rats were cultured with Kae, while intraperitoneal Kae injections were administered to BB rats for 15 days. Quantitative PCR, Western blotting, immunofluorescence, and Spectral Domain - Optical Coherence Tomography (SD-OCT) facilitated survival assessment, cellular signaling analysis, and inflammatory marker determination., Results: Results demonstrate Kae significantly mitigates inflammatory processes across in vitro, ex vivo, and in vivo DR models, primarily targeting immune cell responses. Kae administration notably inhibits proinflammatory responses during DR progression while promoting an anti-inflammatory milieu, chiefly through microglia-mediated synthesis of Arginase-1 and Hemeoxygenase-1(HO-1). In vivo, Kae administration effectively preserves retinal integrity amid DR progression., Conclusions: Our findings elucidate the interplay between retinal and systemic immune cells in DR progression, underscoring a differential treatment response predominantly orchestrated by microglia's anti-inflammatory action. Kae treatment induces a phenotypic and functional shift in immune cells, delaying DR progression, thereby spotlighting microglial cells as a promising therapeutic target in DR management., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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)-β-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.

Chronic wound healing often encounters challenges characterized by prolonged inflammation and impaired angiogenesis. While the immune response plays a pivotal role in orchestrating the intricate process of wound healing, excessive inflammation can hinder tissue repair. In this study, a bilayer alginate hydrogel system encapsulating polyelectrolyte complex nanoparticles (PCNs) loaded with anti-inflammatory cytokines and angiogenic growth factors is developed to address the challenges of chronic wound healing. The alginate hydrogel is designed using two distinct crosslinking methods to achieve differential degradation, thereby enabling precise spatial and temporal controlled release of PCNs. Initially, interleukin-10 (IL-10) is released to mitigate inflammation, while unsaturated PCNs bind and remove accumulated pro-inflammatory cytokines at the wound site. Subsequently, angiogenic growth factors, including vascular endothelial growth factor and platelet-derived growth factor, are released to promote vascularization and vessel maturation. Our results demonstrate that the bilayer hydrogel exhibits distinct degradation kinetics between the two layers, facilitating the staged release of multiple signaling molecules. In vitro experiments reveal that IL-10 can activate the Jak1/STAT3 pathway, thereby suppressing pro-inflammatory cytokines and chemokines while down-regulating inflammation-related genes. In vivo studies demonstrate that application of the hydrogel in chronic wounds using diabetic murine model promotes healing by positively modulating multiple integral reparative mechanisms. These include reducing inflammation, promoting macrophage polarization towards a pro-regenerative phenotype, enhancing keratinocyte migration, stimulating angiogenesis, and expediting wound closure. In conclusion, our hydrogel system effectively mitigates inflammatory responses and provides essential physiological cues by inducing a synergistic angiogenic effect, thus offering a promising approach for the treatment of chronic wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Trained immunity and tolerance are part of the innate immune memory that allow innate immune cells to differentially respond to a second encounter with stimuli by enhancing or suppressing responses. In trained immunity, treatment of macrophages with β-glucan (BG) facilitates the production of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. For the tolerance response, LPS stimulation leads to suppressed inflammatory responses during subsequent LPS exposure. Epigenetic reprogramming plays crucial roles in both phenomena, which are tightly associated with metabolic flux. In this study, we performed a screening of an epigenetics compound library that affects trained immunity or LPS tolerance in macrophages using TNFα as a readout. Among the 181 compounds tested, one compound showed suppressive effects, while 2 compounds showed promoting effects on BG-trained TNFα production. In contrast, various inhibitors targeting Aurora kinase, histone methyltransferase, histone demethylase, histone deacetylase and DNA methyltransferase showed inhibitory activity against LPS tolerance. Several proteins previously unknown to be involved in innate immune memory, such as MGMT, Aurora kinase, LSD1 and PRMT5, were revealed. Protein network analysis revealed that the trained immunity targets are linked via Trp53, while LPS tolerance targets form three clusters of histone-modifying enzymes, cell division and base-excision repair. In trained immunity, the histone lysine methyltransferase SETD7 was identified, and its expression was increased during BG treatment. Level of the histone lysine demethylase, LSD1, increased during LPS priming and siRNA-mediated reduction resulted in increased expression of Il1b in LPS tolerance. Taken together, this screening approach confirmed the importance of epigenetic modifications in innate immune memory and provided potential novel targets for intervention., (© 2022. The Author(s).)

The white-rot fungi Ceriporia lacerata is used in bioremediation, such as lignocellulose degradation, in nature. Submerged cultures and extracts of C. lacerata mycelia (CLM) have been reported to contain various active ingredients, including β-glucan and extracellular polysaccharides, and to exert anti-diabetogenic properties in mice and cell lines. However, the immunostimulatory effects have not yet been reported. This study aimed to identify the immunomodulatory effects, and underlying mechanisms thereof, of submerged cultures of CLM using RAW264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression in mice. Compared to CTX-induced immunosuppressed mice, the spleen and thymus indexes in mice orally administered CLM were significantly increased; body weight loss was alleviated; and natural killer (NK) cytotoxicity, lymphocyte proliferation, and cytokine (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, and interleukin [IL]-2) production were elevated in the serum. In RAW264.7 macrophages, treatment with CLM induced phagocytic activity, increased the production of nitric oxide (NO), and promoted mRNA expression of the immunomodulatory cytokines TNF-α, IFN-γ, IL-1β, IL-6, IL-10, and IL-12. In addition, CLM increased the inducible NO synthase (iNOS) concentration in macrophages, similar to lipopolysaccharide (LPS) stimulation. Mechanistic studies showed that CLM induced the activation of the NF-κB, PI3k/Akt, ERK1/2, and JNK1/2 pathways. Moreover, the phosphorylation of NF-κB and IκB induced by CLM in RAW264.7 cells was suppressed by specific MAPKs and PI3K inhibitors. Further experiments with a TLR4 inhibitor demonstrated that the production of TNF-α, IL-1β, and IL-6 induced by CLM was decreased after TLR4 was blocked. Overall, CLM protected against CTX-induced adverse reactions by enhancing humoral and cellular immune functions, and has potential as an immunomodulatory agent.

The in vitro and in vivo immunoregulatory activity of a water-soluble sulfated fucan AL1-1 from the sea cucumber A. leucoprocta was elucidated. In vitro experiments showed that AL1-1 up-regulated immunostimulatory activities in RAW264.7 cells and that it could successfully promote ROS production and phagocytic activity, increase secretion levels of iNOS, and induce the production of considerable amounts of cytokines (TNF-α, IL-6, IL-1β and IL-12). We found that toll-like receptor 4 (TLR4) was mainly involved in AL1-1 mediated macrophage activation. AL1-1's in vivo immunomodulatory activity on cyclophosphamide (CY)-treated mice was investigated and it was shown that it could strongly enhance Sig A levels, promote the total antioxidant capacity (T-AOC), and reduce malondialdehyde (MDA) level in the intestine. It could also increase activities of superoxidase dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). These results demonstrate that AL1-1 has a significant effect on enhancing in vivo and in vitro immune response., (Copyright © 2021. Published by Elsevier B.V.)

The structures and immunomodulatory activities of two polysaccharides (SDH-WA and SDH-0.2A) from Rehmanniae Radix Praeparata (RRP) were investigated. RRP crude polysaccharide was obtained by water extraction and purified. Ion chromatography, high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, methylation analysis, gas chromatography-mass spectrometry, and nuclear magnetic resonance were used to characterize the polysaccharides. The main chain of SDH-WA was →6)-α-D-Galp-(1→6)-α-D-Galp-(1→5)-α-L-Araf-(1→3,5)-α-L-Araf-(1→, terminal sugar residue α-L-Araf-(1→ linked to residue →3,5)-α-L-Araf-(1→ on the main chain by an O-3 bond. The other two terminal sugar residues α-D-Galp-(1→ and →6)-β-D-Galp were linked to the end of the main chain. The main chain of SDH-0.2A was →2,4)-α-L-Rhap-(1→4)-α-D-GalpA-(1→. Three branched chains α-D-Galp-(1→6)-α-D-Galp-(1→5)-α-L-Araf-(1→3,5)-α-L-Araf-(1→, →3,6)-β-D-Galp-(1→5)-α-L-Araf-(1→, and →4)-β-D-Galp-(1→5)-α-L-Araf-(1→ were linked to the main chain residue →2,4)-α-L-Rhap-(1→ by an O-2 bond. Three terminal sugar residues α-D-Galp-(1→, α-L-Araf-(1→, and →6)-β-D-Galp were linked to the end of the chain. Both polysaccharides showed no cytotoxic effects on and significantly promoted the phagocytic activity of RAW264.7 cells. They dose-dependently improved lysozyme activity and stimulated the production of TNF-α and IL-6 by RAW264.7 cells, but attenuated the secretion of lysozymes, TNF-α, IL-6, IL-1β, and nitric oxide by lipopolysaccharide-induced RAW264.7 cells. The present studies suggest that PRR polysaccharide is a valuable source with immunomodulating., (Copyright © 2021. Published by Elsevier B.V.)

The use of an antibiotic with immunomodulatory properties could be fascinating in treating multifactorial inflammatory conditions such as ulcerative colitis (UC). We report our investigations into the immunomodulatory properties of levornidazole, the S-enantiomer of ornidazole, which displayed a tremendous therapeutic potential in UC induced by dextran sodium sulfate (DSS). Levornidazole administration to DSS-colitic mice attenuated the intestinal inflammatory process, with an efficacy better than that shown by 5-amino salicylic acid. This was evidenced by decreased disease activity index, ameliorated macroscopic and microscopic colon damages, and reduced expression of inflammatory cytokines. Additionally, levornidazole displayed anti-inflammatory activity through Caveolin-1-dependent reducing IL-1β and IL-18 secretion by macrophages contributing to its improvement of the intestinal inflammation, as confirmed in vitro and in vivo. In conclusion, these results pointed out that the immunomodulatory effects of levornidazole played a vital role in ameliorating the intestinal inflammatory process, which would be crucial for the translation of its use into clinical settings., (© 2021. Huazhong University of Science and Technology.)

Background: Fungal cell wall polysaccharides maintain the integrity of fungi and interact with host immune cells. The immunomodulation of fungal polysaccharides has been demonstrated in previous studies. However, the effect of chitin-rich heteroglycan extracted from Sporothrix schenckii sensu stricto on the immune response has not been investigated., Results: In this study, chitin-rich heteroglycan was extracted from S. schenckii sensu stricto, and immunomodulation was investigated via histopathological analysis of skin lesions in a mouse model of sporotrichosis and evaluation of the phagocytic function and cytokine secretion of macrophages in vitro. The results showed that the skin lesions regressed and granulomatous inflammation was reduced in infected mice within 5 weeks. Moreover, heteroglycan promoted the fungal phagocytosis by macrophages and modulated the cytokine secretion. Heteroglycan upregulated TNF-α expression early at 24 h and IL-12 expression late at 72 h after incubation, which might result from moderate activation of macrophages and contribute to the subsequent adaptive immune response., Conclusions: Chitin-rich heteroglycan extracted from S. schenckii sensu stricto potentiated fungal clearance in a mouse model of sporotrichosis. Moreover, chitin-rich heteroglycan promoted fungus phagocytosis by macrophages and modulated cytokines secretion. These results might indicate that chitin-rich heteroglycan could be considered as an immunomodulator used in the treatment of sporotrichosis.

Docosahexaenoyl ethanolamide (DHEA), the ethanolamine conjugate of the n-3 long chain polyunsaturated fatty acid docosahexaenoic acid, is endogenously present in the human circulation and in tissues. Its immunomodulating properties have been (partly) attributed to an interaction with the cyclooxygenase-2 (COX-2) enzyme. Recently, we discovered that COX-2 converts DHEA into two oxygenated metabolites, 13- and 16-hydroxylated-DHEA (13- and 16-HDHEA, respectively). It remained unclear whether these oxygenated metabolites also display immunomodulating properties like their parent DHEA. In the current study we investigated the immunomodulating properties of 13- and 16-HDHEA in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The compounds reduced production of tumor necrosis factor alpha (TNFα), interleukin (IL)-1β and IL-1Ra, but did not affect nitric oxide (NO) and IL-6 release. Transcriptome analysis showed that the compounds inhibited the LPS-mediated induction of pro-inflammatory genes (InhbA, Ifit1) and suggested potential inhibition of regulators such as toll-like receptor 4 (TLR4), MyD88, and interferon regulatory factor 3 (IRF3), whereas anti-inflammatory genes (SerpinB2) and potential regulators IL-10, sirtuin 1 (Sirt-1), fluticasone propionate were induced. Additionally, transcriptome analysis of 13-HDHEA suggests a potential anti-angiogenic role. In contrast to the known oxylipin-lowering effects of DHEA, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analyses revealed that 13- and 16-HDHEA did not affect oxylipin formation. Overall, the anti-inflammatory effects of 13-HDHEA and 16-HDHEA are less pronounced compared to their parent molecule DHEA. Therefore, we propose that COX-2 metabolism of DHEA acts as a regulatory mechanism to limit the anti-inflammatory properties of DHEA., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The nanotechnology has an important role in improving the efficacy and safety in therapy. The present study explains the antifungal and the immunomodulatory potency of propolis nanoparticles (PNPs) against Fusarium solani in Albino Mice. Disc diffusion method was used for antifungal efficacy of PNPs. Moreover, PNPs exhibited a progressive decrease in the % of viable Vero cells and suppressed the virulence factors of Fusarium saloni including adhesion and biofilm formation. In animal experiments, lymphoid cell, peritoneal phagocytes, red blood cell RBCs and white blood cell WBCs counts and the activities of T and B-lymphocytes were determined. In addition, T-cell mitogenesis cells, serum level of interleukin 2 (IL-2) and haemoglobin Hb concentration were measured. PNPs exhibited high inhibition zone with most of Fusarium solani isolates. The results indicated that treatment of mice by PNPs showed a marked rise in the number of cells from thymus, spleen, mesenteric lymph nodes and bone marrow. Furthermore, PNPs caused statistically significant raised in Hb concentration and WBCs count. These results confirmed that many biological activities attributed to PNPs and is as an adjuvant for immune enhancement.