Immunomodulatory effects of Pseudostellaria heterophylla peptide on spleen lymphocytes via a Ca2+/CaN/NFATc1/IFN-γ pathway

2019 ◽  
Vol 10 (6) ◽  
pp. 3466-3476 ◽  
Author(s):  
Qian Yang ◽  
Xixi Cai ◽  
Muchen Huang ◽  
Lee Jia ◽  
Shaoyun Wang

Screening and isolation of Pseudostellaria heterophylla peptide with immunomodulatory activity via a Ca2+/CaN/NFATc1/IFN-γ pathway.

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3460
Author(s):  
Tiago A. Conde ◽  
Luís Mendes ◽  
Vítor M. Gaspar ◽  
João F. Mano ◽  
Tânia Melo ◽  
...  

The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN-γ-stimulated) incubated with non-cytotoxic concentrations of three flavonoids: quercetin, naringin and naringenin. One hundred forty-seven PL species belonging to various classes were identified, and their relative abundances were determined. Each flavonoid displayed its own unique signature of induced effects. Quercetin produced the strongest impact, acting both on constitutive PLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minor signaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely, naringin hardly affected structural PLs, producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages. In turn, albeit sharing some effects with quercetin, naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin. These results demonstrate that flavonoids bioactivity involves profound and specific remodeling of macrophage phospholipidome, paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yi Cheng ◽  
Lu Liu ◽  
Simei Mo ◽  
Jianxiong Gao ◽  
Hongjian Zhang ◽  
...  

Cyclophosphamide is a commonly used anticancer drug, and immunosuppression is one of the most common side effects. How to recover the immunological function is important for cyclophosphamide-treated patients. In the present study, Phellodendri Cortex polysaccharides (CPP) could enhance the proliferation of mouse spleen lymphocytes in vitro. The immunoregulatory function of CPP was then investigated in cyclophosphamide-induced immunosuppressed mice. In CPP-treated groups, mice were orally treated with CPP at doses of 1, 0.5, and 0.25 g/kg bodyweight from 1 to 11 d, respectively. The cyclophosphamide was administrated in CPP and cyclophosphamide groups from 12 to 14 d. In the cyclophosphamide and normal control groups, the mice received equal volume of saline from 1 to 14 d. The results showed that CPP (1 g/kg) could significantly increase the bodyweight of mice, even during cyclophosphamide treatment. The organ coefficients of the spleen and thymus were recovered by CPP treatment. CPP upregulated the contents of cytokines (IL-2, IL-6, IFN-γ, and TNF-α) in serum, which were downregulated by cyclophosphamide. The mRNA levels of these cytokines were also elevated by CPP treatment in the spleen. Cyclophosphamide upregulated the expressions of NF-κB p65, TLR4, and MyD88, suggesting that the NF-κB signaling pathway was activated by cyclophosphamide. After CPP treatment, it was recovered to normal level. These results indicated that CPP alleviated the cyclophosphamide-induced immunosuppression.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3899
Author(s):  
Amanda Gabrielle Barros Dantas ◽  
Rafael Limongi de de Souza ◽  
Anderson Rodrigues de de Almeida ◽  
Francisco Humberto Xavier Xavier Júnior ◽  
Maira Galdino da Rocha Pitta ◽  
...  

Carvacrol (CV) is an essential oil with numerous therapeutic properties, including immunomodulatory activity. However, this effect has not been studied in nanoemulsion systems. The objective of this study was to develop an innovative carvacrol-loaded nanoemulsion (CVNE) for immunomodulatory action. The developed CVNE comprised of 5% w/w oily phase (medium chain triglycerides + CV), 2% w/w surfactants (Tween 80®/Span 80®), and 93% w/w water, and was produced by ultrasonication. Dynamic light scattering over 90 days was used to characterize CVNE. Cytotoxic activity and quantification of cytokines were evaluated in peripheral blood mononuclear cell (PBMC) culture supernatants. CVNE achieved a drug loading of 4.29 mg/mL, droplet size of 165.70 ± 0.46 nm, polydispersity index of 0.14 ± 0.03, zeta potential of −10.25 ± 0.52 mV, and good stability for 90 days. CVNE showed no cytotoxicity at concentrations up to 200 µM in PBMCs. CV diminished the production of IL-2 in the PBMC supernatant. However, CVNE reduced the levels of the pro-inflammatory cytokines IL-2, IL-17, and IFN-γ at 50 µM. In conclusion, a stable CVNE was produced, which improved the CV immunomodulatory activity in PBMCs.


1992 ◽  
Vol 20 (03n04) ◽  
pp. 233-243 ◽  
Author(s):  
Yee-Shin Lin ◽  
Hsuch-Ching Chiang ◽  
Woei-Song Kan ◽  
Emily Hone ◽  
Shyh-Jen Shih ◽  
...  

The immunomodulatory effects of Physalis angulata L. extract fraction VII (PA-VII), PA-VII-A, PA-VII-B and PA-VII-C were investigated in this study. The results showed that PA-VII and PA-VII-C strongly enhanced blastogenesis response, PA-VII-B had moderate activity, and PA-VII-A exerted only slight effect on cell proliferation. A synergistic effect was observed when the suboptimal dosage of phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was added to the culture. Furthermore, PA-VII and PA-VII-C possessed stimulatory activity on B cells and less effect on T cells. The antibody responses were also augmented by PA-VII, PA-VII-B and PA-VII-C, but not by PA-VII-A. The enhancement of antibody response could be observed both in BALB/c and C3H/HeJ mice.


Author(s):  
Yuandani Yuandani ◽  
Edy Suwarso

Objective: This study was conducted to evaluate the immunomodulatory effects of ethanol extract of Curcuma mangga by in vivo study.Methods: The ethanol extract of C. mangga was comprised to carbon clearance method for its immunomodulatory potential. The extract wasadministered orally at doses of 100, 200, and 400 mg/kg BW to mice for 7 days. On day 8, carbon ink was injected, and the blood was collected formeasurement of elimination of carbon. Total leukocyte count was also determined.Results: The evaluation of immunomodulatory potential of ethanol extract of C. mangga revealed a dose-dependent increase in phagocytosis ability.The phagocytic index of ethanol extract of C. mangga was more than those of negative control, indicating the immunostimulatory activity of C. mangga.It showed low stimulation on total leukocyte count.Conclusion: The results indicate that ethanol extract of C. mangga rhizomes possesses immunomodulatory activity and has therapeutic potential forthe treatment of infectious diseases.


2020 ◽  
Vol 8 (8) ◽  
pp. 1175
Author(s):  
Sun Woo Jin ◽  
Gi Ho Lee ◽  
Min Jung Jang ◽  
Gyeong Eun Hong ◽  
Jae Young Kim ◽  
...  

Recently, Lactococcus lactis subsp. lactis has been reported to have immunostimulating properties in an immunosuppressed-animal model. However, the immunological activities of Lactococcus lactis and the molecular mechanisms remain unclear. In this report, we evaluated the immunostimulating activity and associated mechanisms of Lactococcus lactis subsp. lactis GCWB1176 (GCWB1176) in macrophages and cyclophosphamide (CTX)-induced immunosuppressed mice. In a series of safety tests, GCWB1176 was found to have a negative response to hemolysis, as well as susceptibility to antibiotics. Administration of GCWB1176 elevated natural killer (NK) cell activities; concanavalin A-induced T cell proliferation; and serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-10 and IL-12 in CTX-induced immunosuppressed mice. In RAW264.7 macrophages, treatment with GCWB1176 induced phagocytic activity and increased the production of nitric oxide (NO) and expression of inducible NO synthase. Simultaneously, GCWB1176 increased the production of TNF-α, IFN-γ, IL-1β, IL-10 and IL-12 from mouse splenocytes and RAW264.7 cells. In addition, GCWB1176 significantly increased the transcriptional activities of NF-κB and iNOS. Taken together, GCWB1176 improved immune function through the activation of macrophages and NK cells. These findings suggest that dietary supplementation of GCWB1176 may be used to enhance immunity.


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5733
Author(s):  
Feng Liu ◽  
Lijia Zhang ◽  
Xi Feng ◽  
Salam A. Ibrahim ◽  
Wen Huang ◽  
...  

The effects of immunomodulatory activity of two types of carboxymethyl pachymaran (CMP-1 and CMP-2) on cyclophosphamide (CTX)-induced mice were investigated. Both CMP-1 and CMP-2 were found to restore the splenomegaly and alleviate the spleen lesions and the mRNA expressions of TLR4, MyD88, p65 and NF-κB in spleen were also increased. CMP-1 and CMP-2 could enhance the immunity by increasing the levels of TNF-α, IL-2, IL-6, IFN-γ, Ig-A and Ig-G in serum. In addition, CMP-1 could increase the relative abundance of Bacteroidetes and reduce the relative richness of Firmicutes at the phylum level. CMP-1 and CMP-2 could reduce the relative abundance Erysipelatoclostridum at the genus level. CMP-1 and CMP-2 might enhance the immune function of immunosuppression mice by regulating the gene expression in the TLR4/NF-κB signaling pathway and changing the composition and abundance of the intestinal microbiota. The results suggested that CMP-1 and CMP-2 would be as potential immunomodulatory agents in functional foods.


Author(s):  
Adryan Fristiohady ◽  
Jumadil ◽  
Wahyuni ◽  
Muh. Hajrul Malaka ◽  
Wa Ode Harnita ◽  
...  

Xestospongia sp. is one of marine sponge belongs to demosponges class that mainly found in Southeast Sulawesi and the secondary metabolites contained in Xestospongia sp. suspected to have immunomodulatory activity. A previous study exhibited the immunomodulatory of Xestospongia sp. ethanolic extract (XEE) at dose of 300 and 400 mg/Kg BW by affecting the phagocytic activity of macrophages. Thus, this study aims to investigate the effect of XEE towards interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) at dose of 300 and 400 mg/Kg BW. Wistar male rats are divided into 4 groups (n=6) randomly and treated for 7 days orally each as follow: group I (XEE dose of 300 mg/KgBW); group II (XEE dose of 400 mg/KgBW); group III (0.5% NaCMC); and group IV (commercial phylantii extract). On day 8, animals were infected with Staphylococcus aureus and left for 1 hour. Animals were sacrificed and the blood was drawn by cardiac puncture (3 mL), followed by analyzed under ELISA Kit for IFN-γ and TNF-α. Collected data were analyzed statistically using SPSS®. The IFN-γ levels obtained were 350.113; 392.970; 118.416; and 61.958 ρg/mL, respectively and the TNF-α were 2808; 1308; 778; and 845.5 ρg/mL, respectively. According to results obtained, both doses of XEE are affecting the IFN-γ and TNF-α levels (p<0.05) compared to group III as negative control, and group IV as positive control. As conclusion, XEE of both doses is increasing IFN-γ and TNF-α levels of animals that respond to phagocytic activity


2021 ◽  
Author(s):  
◽  
Vimal Patel

<p>Understanding the immunomodulatory activities of compounds is important to identify the unintended adverse immunomodulatory effects of therapeutic compounds in development and to select novel compounds that may provide benefit for those diagnosed with immunemediated disorders. In both these cases, it is desirable to identify compounds with immunomodulatory activity early in the drug discovery process in a medium-throughput format. A screening strategy has been designed to fulfil these needs.  The first step in designing the strategy was to select informative assays and optimise individual assays to suit medium-throughput drug discovery. These individual assays investigated effects on a broad range of functions associated with innate and adaptive immune cells including macrophages (activation, cytokine production, phagocytosis and motility), helper T cells (activation and cytokine production), cytotoxic T cells (degranulation and cytokine production), and B cells (antibody production and cytokine production). Cost effectiveness and ease-of-use were important considerations during assay design and optimisation.  Using a compound set comprised of positive controls (i.e. compounds known to alter specific immune functions), a data set was generated to guide the strategy design. Assays were ordered to efficiently use resources and reduce the generation of less informative data. Additionally, using data collected from this compound set, strategies to assess and identify immunomodulatory activity were built and analysed. A second set of compounds was used to validate the screening strategy, and this screen highlighted new and novel activities for these known compounds that suggests they possess additional immunomodulatory effects.  Once validated, several novel compounds were run through the screen, including a traditional Samoan medicine, a heparan sulfate mimetic, and a novel anti-cancer agent; unique immunomodulatory activities were discovered. Finally, a hierarchical cluster analysis was used to cluster compounds sharing similar activity profiles and suggested the potential to develop further statistical methods to provide insight into compound characterisation. Together, this research has developed and validated a novel, medium throughput drug discovery system that can facilitate the identification of the immunomodulatory activities of compounds in the drug discovery environment.</p>


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12575
Author(s):  
Xianghui Li ◽  
Zhiqiang Zhang ◽  
Zhenhuan Guo ◽  
Li Zhao ◽  
Yonglu Liu ◽  
...  

Nanoemulsions (NE) are used widely in pharmaceutical drug formulations and vaccine preparation, and Acanthopanax senticousus polysaccharide (ASPS) is a natural bioactive compound with immunostimulatory activity. Therefore, NE-loaded ASPS is expected to provide immunological enhancement for effective treatment. In the present study, Acanthopanax senticousus polysaccharide (ASPS was encapsulated into nanoemulsions, the resultant ASPS–NE were coated with a negative charge, and the immune enhancement mechanism of these ASPS-NE formulations was analyzed. The immunosuppressive animal models (70 ICR mice, male) for the study were established using cyclophosphamide. In addition, the activation of splenocyte proliferation, phagocytosis of the macrophages, the ratio of CD4+ to CD8+, the concentrations of the cytokines in serum, Western blot analysis was used for the analysis of the P65/JNK/ikk α signaling pathway in the peritoneal macrophage s. The results revealed that the ASPS-NE could stimulated the proliferation of splenocytes and enhance immunity. The ASPS-NE induced the expression of different cytokines (TNF-α, IFN-γ, IL-2, and IL-6), could activate the expressions of P65, JNK, and ikkα, and regulated the Th1/Th2 cytokines. These findings demonstrated the potential of ASPS-NE formulations for drug delivery and to induce potent and sustained immune responses.


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