Search Results (32)

Background/objectives: This study evaluated the immunoenhancing effects of Agastache rugosa extract in a cyclophosphamide-induced immunosuppressed mouse model. Methods: Jeju A. rugosa was processed via hot water extraction and 20% ethanol extraction. For immunosuppression induction, 7-week-old male BALB/c mice received intraperitoneal CPA injections (150 mg/kg, day −3; 110 mg/kg, day −1), followed by oral administration of hot water extract (ARE-W) and ethanol extract (ARE-E) at 100 and 300 mg/kg for 14 days. Oral administration of ARE-W and ARE-E was started on day 0, immediately following the final CPA injection on day −1. Immune function was assessed through body weight changes, spleen weight, NK cell activity, IFN-γ production, and splenic lymphocyte proliferation. Results: Results demonstrated that CPA treatment induced comprehensive immune dysfunction, while A. rugosa extracts significantly ameliorated these immunosuppressive conditions. Notably, ARE-W (300 mg/kg) significantly enhanced NK cell cytotoxicity against tumor cells and IFN-γ production compared to the CPA group, and effectively restored spleen weight and lymphocyte proliferation. ARE-E also exhibited dose-dependent immune function recovery; however, ARE-W showed superior efficacy across most immune parameters. Conclusions: These findings suggest that A. rugosa extract, particularly ARE-W, effectively restores immune function in immunosuppressed conditions, indicating potential application as a natural functional material for ameliorating immunosuppression caused by cancer treatment or immune diseases. Full article

Background: Canine parvovirus (CPV) is a highly pathogenic virus that predominantly affects puppies, with mortality rates exceeding 70%. Although commercial multivalent live attenuated vaccines (MLV) are widely employed, their efficacy is often compromised by maternal antibody interference. Consequently, the development of novel vaccines remains imperative for effective CPV control. Methods: Recombinant CPV VP2 protein (rVP2) and canine interlukine 12 protein (rcIL-12) were expressed using the Bac-to-Bac baculovirus expression system and the biological activity of these proteins was assessed through hemagglutination, Cell Counting Kit-8 (CCK8) and IFN-γ induction assays. The combined immunoenhancement effect of rVP2 and rcIL-12 protein was evaluated in puppies. Results: Both rVP2 and rcIL-12 were successfully expressed and purified, exhibiting confirmed antigenicity, immunogenicity, and bioactivity. Co-administration of rVP2 with rcIL-12 elicited higher neutralizing antibody titer (6–7 times higher), complete challenge protection efficiency (no clinical symptoms and tissue and organ lesions), fewer viral shedding (decreasing significantly 8-day post challenge) and superior viral blockade (lower viral load in the organism) compared to rVP2 alone. Conclusions: Our findings demonstrate that rVP2 co-administered with rcIL-12 induces robust protective immunity in puppies and significantly mitigated the inhibitory effects of maternal antibodies. This represents a promising strategy for enabling earlier vaccination in puppies and rational design of CPV subunit vaccines. Full article

Background: This systematic review aimed to evaluate the efficacy of immunoenhancing nutritional therapy compared to conventional nutritional care in reducing perioperative complications in adult patients undergoing surgery for oral cancer. Given the unclear role of immunonutrition in this specific surgical setting, we synthesized available randomized controlled trials to assess outcomes such as surgical site infections, wound healing complications, hospital stay, and adverse events. Methods: Patients who underwent planned oral cancer surgery were included. The intervention group received oral or enteral immunoenhancing nutritional agents preoperatively, postoperatively, or both, while the control group received standard care (intravenous fluids) and/or macromolecular nutritional supplements. PubMed, Cochrane CENTRAL, and Central Medical Journal were comprehensively searched for randomized controlled trials (RCTs); eight RCTs were included. The primary outcomes were mortality, suture/healing failure, surgical site infection (SSI), and hospital stay length, with evidence certainty assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results: Although mortality estimation was not feasible, hazard ratios from the meta-analysis showed that the intervention significantly improved suture/healing failure, SSI, and hospital stay length. The certainty of evidence was “low” for suture/healing failure and SSI and “moderate” for hospital stay length. Conclusions: Perioperative management with enteral nutritional agents fortified with immunonutrients should be considered in adult patients scheduled for (advanced) oral cancer surgery. Full article

A novel hexapeptide LVVLGH (LH-6) from the thick-shelled mussel (Mytilus coruscus) demonstrated potent immune-enhancing effects in RAW264.7 cells in vitro, but its immunological activity in vivo is unclear. As a result, the present study was designed to investigate the in vivo effects of LH-6 on cyclophosphamide-induced immunodeficient mice. The results demonstrate that LH-6 promoted the growth and development of immunodeficient mice in a concentration-dependent manner, remarkably elevated the immune organ index, and relieved the pathological characteristics of the spleen and thymus. Additional experiments also revealed that LH-6 effectively promoted the multiplication of splenic lymphocytes and natural killer activity, enhanced the function of abdominal macrophages, and apparently recovered delayed-type hypersensitivity in immunodeficient mice. The secretion of IgA, IgG, IgM, TNF-α, IL-1β, IL-6, and serum hemolysin were remarkably improved by LH-6, suggesting that LH-6 can synergistically strengthen cellular and humoral immunity. In addition, LH-6 promoted the phosphorylation of IκBα and nuclear translocation of p65, which correspondingly increased the phosphorylation levels of p38, JNK, and ERK; activated the NF-κB and MAPK pathways; and exerted in vivo immunomodulatory activities. Docking results show that LH-6 has favorable binding energies to candidate proteins in the NF-κB and MAPK pathways. To summarize, this research further demonstrated that LH-6 possesses in vivo immunomodulatory activity, which provides a possibility for the subsequent development of immune-enhancing functional foods. Full article

Probiotic fermentation can promote the release of more effective components from traditional Chinese medicines (TCMs). Astragalus membranaceus (Fisch.) Bunge (A. membranaceus) and Raphani Semen are TCMs that have gained attention for their immunoenhancing activities. This study aimed to investigate the effects and underlying mechanisms of probiotic-fermented A. membranaceus and Raphani Semen (PROAS) in cyclophosphamide (CTX)-induced immunocompromised mice. Changes in the composition of A. membranaceus and Raphani Semen after fermentation by probiotic strains, including Bifidobacterium longum SD5219, Lactobacillus fermentum NCIMB5221, and Lactobacillus paracasei SD5219, were identified using high-performance liquid chromatography. The immunostimulatory effects and mechanisms of PROAS were evaluated in immunosuppressed mice 3 and 7 days after CTX treatment. Probiotic fermentation of TCMs resulted in changes in major bioactive components. PROAS supplementation effectively restored intestinal integrity in CTX-treated mice by upregulating the mRNA expression of the tight junction proteins. PROAS significantly ameliorated the reduction in the spleen index and number of B lymphocytes caused by CTX treatment and regulated the secretion of cytokines in serum and colon tissues. PROAS administration modulated gut microbial dysbiosis and short-chain fatty acid (SCFA) content in CTX-treated mice. These results suggest that PROAS enhances B lymphocyte function by increasing the regulation of intestinal microbiota to produce high levels of SCFA, repairs the intestinal barrier damage induced by CTX, and promotes intestinal mucosal immunity. Full article

Mycoplasma hyopneumoniae (Mhp) infection severely affects the daily weight gain and feed-to-meat ratio of pigs, while secondary infections with other pathogens can further lead to increased mortality, causing significant economic losses to the pig industry. CD40L is a molecular adjuvant that enhances the cellular and humoral immune responses to vaccines. In this study, the CD40L peptide was fused to the C-terminus of the chimeric P97R1P46P42 protein by genetic engineering using the pFastBac Dual vector. The recombinant chimeric protein P97R1P46P42 and its fusion P97R1P46P42-CD40L were expressed in Sf9 cells and purified. Mice were immunized with P97R1P46P42 or its fusion protein. Seppic ISA 201 emulsified protein, conventional Mhp vaccine and PBS control groups were included. Immunogenecity was assessed by specific IgG antibody response, splenic lymphocyte proliferation, and cytokine IL-4 and IFN-γ levels. We found that CD40L fusion significantly enhanced specific antibody response, lymphocyte proliferation and IL-4 level in the immunized mouse sera as compared to the P97R1P46P42 or conventional vaccine group. This study provides clear evidence that CD40L potentiates the humoral and cellular immune responses to the Mhp chimeric protein P97R1P46P42 in the mouse model. This CD40L-fused chimeric protein could be a MPS subunit vaccine candidate to be tested for its efficacy in pigs in response to challenges with pathogenic Mycoplasma hyopneumoniae strain(s). Full article

The structure and characteristics of LEOPs, β-oligosaccharides from the fruiting body of Lentinus edodes obtained via acid degradation and gel permeation chromatography, were investigated. We performed high-performance liquid chromatography, infrared spectroscopy, methylation analysis, nuclear magnetic resonance, and correlated activity experiments, including antioxidant, immunomodulatory, and liver injury protection to gain insights. LEOPs comprised an oligosaccharide (Mw 2445 Da) based on six β-1, 3-D-glucose residues as the main chain and six β-1, 6-D-glucose residues as the side chain. Surface plasmon resonance analysis indicated that LEOPs directly bound to dectin-1, which facilitated their immunoenhancing activity via downstream NF-κB activation. The results implied that LEOPs may be the active unit of the shiitake β-glucan. The determination of LEOPs structure was performed to reveal the anti-tumor effect and immune-regulatory function of shiitake β-glucan on a molecular level to provide a basis. Full article

In this study, a mixture of Platycodon grandiflorum, Pyrus serotina, Chaenomeles sinensis, and Raphanus sativus (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E₂ (PGE₂) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of IL-4. PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages. Full article

Polysaccharides extracted from Taxus media hrough an aqueous method were further refined by removing proteins via the Sevag technique and purified by dialysis. The separation of these polysaccharides was accomplished using a DEAE-cellulose chromatog-raphy column, yielding two distinct fractions, named CPTM-P1 and CPTM-P2. Notably, CPTM-P1 emerged as the primary polysaccharide component within Taxus media. Consequently, a comprehensive analysis focusing exclusively on CPTM-P1 was undertaken. The molecular weight of CPTM-P1 was established through gel permeation chromatography (GPC), and its monosaccharide composition was deciphered using HPLC-MS. The structure was further elucidated through nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of CPTM-P1 was determined to be 968.7 kDa. The monosaccharide composition consisted of galactose (Gal), arabinose (Ara), galacturonic acid (Gal-UA), glucose (Glc), rhamnose (Rha), xylose (Xyl), mannose (Man), fucose (Fuc), glucuronic acid (Glc-UA), and ribose (Rib). The proportional distribution of these components was 30.53%, 22.00%, 5.63%, 11.67%, 11.93%, 1.69%, 8.50%, 1.23%, 5.63%, and 1.17%, respectively. This confirmed CPTM-P1 as an acidic heteropolysaccharide with a glycuronic acid backbone. Moreover, CPTM-P1 showed immunoenhancing properties, effectively augmenting the secretion of nitric oxide and cytokines (TNF-α, IL-1β, and IL-6). Additionally, it significantly enhances the phagocytic capacity of RAW264.7 cells. These findings underscore the potential application of these polysaccharides in functional foods and pharmaceuticals, providing a solid scientific basis for further exploration and utilization of Taxus media polysaccharides. Full article

In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night’s darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role. Circulating MLT may stimulate both innate and acquired immune responses through its circadian action and by activating high-affinity receptors on immunocompetent cells. Extra-pineal MLT may have antioxidant and anti-inflammatory effects that dampen the innate immune response. These two seemingly divergent roles may be considered to be two sides of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effects of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility of integrating the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite of the fact that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use. Full article

This study investigates the immunomodulatory potential of Galium aparine L. (GAE) in immunodeficient animals. In this study, animals were categorized into five groups: the normal group, CYP group (cyclophosphamide intraperitoneal injection), GA5 group (cyclophosphamide + 5 μg GAE), GA50 group (cyclophosphamide + 50 μg GAE), and GA500 group (cyclophosphamide + 500 μg GAE). The CYP group exhibited significantly reduced spleen weights compared to the normal group, while the groups obtaining GAE displayed a dose-dependent increase in spleen weight. Furthermore, the GAE demonstrated dose-dependent enhancement of splenocyte proliferating activity, with significant increases observed in both LPS and ConA-induced assays. NK cell activity significantly increased in the GA50 and GA500 groups compared to the CYP group. Cytokine analysis revealed a significant increase in IL-6, TNF-α, and IFN-γ levels in ConA-induced splenocytes treated with GAE. Gene expression analysis identified 2434 DEG genes in the extract groups. Notable genes, such as Entpd1, Pgf, Thdb, Syt7, Sqor, and Rsc1al, displayed substantial differences in individual gene expression levels, suggesting their potential as target genes for immune enhancement. In conclusion, Galium aparine L. extract exhibits immunomodulatory properties. The observed gene expression changes further support the potential of Galium aparine L. extract as a natural agent for immune augmentation. Full article

The COVID-19 pandemic remarkably accelerated vaccine research progress. The role of adjuvants in enhancing vaccine immune intensity and influencing immune types has been considered. Ginseng polysaccharide (GPS) has been demonstrated to have strong immunoregulatory properties. It is important to explore the feasibility of adding GPS to vaccine adjuvant components to improve the immune response effect of RBD vaccines. Here, we prepared a SARS-CoV-2 RBD antigen using the Escherichia coli expression system and determined that subcutaneous administration of GPS at a dose of 40 mg/kg could effectively activate dendritic cells (DCs) and macrophages (MΦ) in mice. Compared with the RBD group, the RBD+GPS triggered stronger and persistent antibody responses. It is also notable that higher levels of RBD-specific IgG and IgA were distributed in the lungs of RBD+GPS-immunized BALB/c mice. In addition, the RBD+GPS also resulted in lower percentages of IFN-γ⁺ CD4⁺ T cells and higher percentages of IFN-γ⁺ CD8⁺ T cells and CD8⁺ Tcm cells. These results suggest that GPS could be a promising vaccine immuno-enhancer for SARS-CoV-2 RBD subunit vaccines to establish stronger systemic and pulmonary mucosal protective immunity. Full article

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor 7 (BC-05). BC-05 exhibited potent inhibitory activity on both human CD13 (IC₅₀ = 0.13 μM) and the 20S proteasome (IC₅₀ = 1.39 μM). Although BC-05 displayed lower anti-proliferative activity than that of ixazomib in vitro, an advantage was established in the in vivo anti-cancer efficacy and prolongation of survival time, which may be due to its anti-metastatic and immune-stimulating activity. A pharmacokinetic study revealed that BC-05 is a potentially orally active agent with an F% value of 24.9%. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma. Full article

This study aimed to investigate the immunoenhancement effects of low molecular weight peptides (SCHPs-F1) from red shrimp (Solenocera crassicornis) head against cyclophosphamide (CTX)-induced immunosuppressed mice. ICR mice were intraperitoneally injected with 80 mg/kg CTX for 5 consecutive days to establish the immunosuppressive model and then intragastrically administered with SCHPs-F1 (100 mg/kg, 200 mg/kg, and 400 mg/kg) to investigate its improving effect on immunosuppressed mice and explore its potential mechanism using Western blot. SCHPs-F1 could effectively improve the spleen and thymus index, promoting serum cytokines and immunoglobulins production and upregulating the proliferative activity of splenic lymphocytes and peritoneal macrophages of the CTX-treated mice. Moreover, SCHPs-F1 could significantly promote the expression levels of related proteins in the NF-κB and MAPK pathways in the spleen tissues. Overall, the results suggested that SCHPs-F1 could effectively ameliorate the immune deficiency caused by CTX and had the potential to explore as an immunomodulator in functional foods or dietary supplements. Full article

Gastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance immune function. Our current work assessed the antitumor mechanism of λ-COS using BGC-823 cells. Our findings indicated that λ-COS alone did not have a significant impact on BGC-823 cells in vitro; however, it was effective in inhibiting tumor growth in vivo. When THP-1 cells were pre-incubated with λ-COS and used to condition the medium, BGC-823 cells in vitro displayed a concentration-dependent induction of cell apoptosis, nuclear damage, and the collapse of mitochondrial transmembrane potential. These findings suggested that the antineoplastic effect of λ-COS was primarily due to its immunoenhancement property. Treatment with λ-COS was found to significantly enhance the phagocytic capability of macrophages, increase the secretion of TNF-α and IFN-γ, and improve the indexes of spleen and thymus in BALB/c mice. In addition, λ-COS was found to inhibit the growth of BGC-823-derived tumors in vitro by activating the Par-4 signaling pathway, which may be stimulated by the combination of TNF-α and IFN-γ. When used in combination with 5-FU, λ-COS demonstrated enhanced anti-gastric carcinoma activity and improved the immunosuppression induced by 5-FU alone. These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy. Full article