PMID: 

Endocr Metab Immune Disord Drug Targets. 2020 03 13. Epub 2020 Mar 13. PMID: 32167433

Abstract Title: 

Red Grape Polyphenol Oral Administration Improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis

Abstract: 

BACKGROUND: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine.OBJECTIVE: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients.METHOD: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded.RESULT: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1.CONCLUSION: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

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PMID: 

Int Immunopharmacol. 2017 Sep ;50:194-201. Epub 2017 Jun 30. PMID: 28672215

Abstract Title: 

Silymarin impacts on immune system as an immunomodulator: One key for many locks.

Abstract: 

Silymarin is a flavonoid complex extracted from the Silybum marianum plant. It acts as a strong antioxidant and free radical scavenger by different mechanisms. But in addition to antioxidant effects, silymarin/silybin reveals immunomodulatory affects with both immunostimulatory and immunosuppression activities. Different studies have shown that silymarin has the anti-inflammatory effect through the suppression of NF-κB signaling pathway and TNF-α activation. It also has different immunomodulatory activities in a dose and time-dependent manner. As an immunomodulator agent, silymarin inhibits T-lymphocyte function at low doses while stimulates inflammatory processes at high doses. Studies have shown that silymarin has attenuated autoimmune, allergic, preeclampsia, cancer, and immune-mediated liver diseases and also has suppressed oxidative and nitrosative immunotoxicity. Silymarin also has indicated dual effects on proliferation and apoptosis of different cells. In conclusion, based on the current review,silymarin has a broad spectrum of immunomodulatory functions under different conditions. Recognizing the exact mechanisms of silymarin on cellular and molecular pathways would be very valuable for treatment of immune-mediated diseases. Also further studies are needed to assess the utility of silymarin in protection against autoimmune, cancer, allergic and other diseases in human subjects.

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PMID: 

Inflammation. 2019 Aug ;42(4):1203-1214. PMID: 30806958

Abstract Title: 

Silymarin Restores Regulatory T Cells (Tregs) Function in Multiple Sclerosis (MS) Patients In Vitro.

Abstract: 

Dysregulation of the immune system and impairment in the function and number of patient-derived regulatory T cells (Treg) have an important role in multiple sclerosis (MS) pathogenesis. MS patients still receive different medications to overcome the relapses and to slow the disease progression. However, the benefits of these therapies are limited and are accompanied by different side effects. The immunoregulatory effects of Silymarin as a plant-derived flavonoid have shown in studies. In the present study, regulatory T cells (Tregs) were isolated from MS patients who diagnosed as new cases and IFN-β-treated RRMS patients. Isolated Treg cells were cultured in the presence of different concentrations of Silymarin (50, 100, 150 μM) for 48, 72, and 120 h. Proliferation and activation of Treg cells were assessed by flow cytometry. Also, FOXP3, JAK3, and STAT5 gene expression, IL-10, and TGF-βproduction by Tregs were evaluated by real-time PCR and ELISA respectively. The results showed that Silymarin promoted Treg proliferation at 100 μM concentration after 72 h. Additionally, IL-10, TGF-β levels, and FOXP3, JAK3, and STAT5 gene expression enhanced by Silymarin dose and time dependently. Our preliminary results suggest that the induction and activation of Tregs could be an underlying mechanism of the ancient used herbal medicine Silymarin, providing effective means against autoimmune and inflammatory diseases.

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PMID: 

Sci Rep. 2020 Mar 24 ;10(1):5345. Epub 2020 Mar 24. PMID: 32210304

Abstract Title: 

Lactobacillus reuteri 5454 and Bifidobacterium animalis ssp. lactis 5764 improve colitis while differentially impacting dendritic cells maturation and antimicrobial responses.

Abstract: 

Crohn's disease is linked to a decreased diversity in gut microbiota composition as a potential consequence of an impaired anti-microbial response and an altered polarization of T helper cells. Here, we evaluated the immunomodulatory properties of two potential probiotic strains, namely a Bifidobacterium animalis spp. lactis Bl 5764 and a Lactobacillus reuteri Lr 5454 strains. Both strains improved colitis triggered by either 2,4,6-trinitrobenzenesulfonic acid (TNBS) or Citrobacter rodentium infection in mice. Training of dendritic cells (DC) with Lr 5454 efficiently triggered IL-22 secretion and regulatory T cells induction in vitro, while IL-17A production by CD4T lymphocytes was stronger when cultured with DCs that were primed with Bl 5764. This strain was sufficient for significantly inducing expression of antimicrobial peptides in vivo through the Crohn's disease predisposing gene encoding for the nucleotide-binding oligomerization domain, containing protein 2 (NOD2). In contrast, NOD2 was dispensable for the impact on antimicrobial peptide expression in mice that were monocolonized with Lr 5454. In conclusion, our work highlights a differential mode of action of two potential probiotic strains that protect mice against colitis, providing the rational for a personalized supportive preventive therapy by probiotics for individuals that are genetically predisposed to Crohn's disease.

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PMID: 

Microorganisms. 2020 Mar 27 ;8(4). Epub 2020 Mar 27. PMID: 32230910

Abstract Title: 

The Exopolysaccharide ofUCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance againstInfection.

Abstract: 

UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages afterinfection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection againstinfection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of-infected mice. The differential cytokine profile induced by Lf979C in-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance againstinfection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.

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PMID: 

Am J Chin Med. 2019 ;47(4):823-839. Epub 2019 May 15. PMID: 31091972

Abstract Title: 

Immunostimulating and Antimetastatic Effects of Polysaccharides Purified from Ginseng Berry.

Abstract: 

Ginseng root has been used in traditional oriental medicine for the enhancement of immune system function. The immunostimulatory effects of ginseng berry polysaccharides, however, remain unclear. Effects of polysaccharides from ginseng berry on the activation of natural killer (NK) cells and inhibition of tumors are reported. A crude polysaccharide was isolated from ginseng berry as a ginseng berry polysaccharide portion (GBPP) and was further fractionated using gel filtration chromatography to obtain the three polysaccharide fractions GBPP-I, -II and -III. GBPP-I consisted of mainly galactose (46.9%) and arabinose (27.5%). GBPP-I showed a high dose-dependent anticomplementary activity. Stimulation of murine peritoneal macrophages by GBPP-I showed the greatest enhancement of interleukin (IL)-6 and IL-12 and tumor necrosis factor (TNF)-production. In addition, anassay of natural killer (NK) cell activity showed that oral (administration of GBPP-I significantly increased NK cell cytotoxicity in YAC-1 tumor cells and production of granzyme B. Prophylactic intravenous (andadministration of GBPP-I significantly and dose-dependently inhibited lung metastatic activity in B16BL6 melanoma cells. Depletion of NK cells after injection of rabbit anti-asialo GM1 partially abolished the inhibitory effect of GBPP-I on lung metastasis, indicating that NK cells play an important role in anticancer effects. GBPP-I exerts a strong immune-enhancing activity and can prevent cancer metastasis through activation of NK cells and other immune-related cells.

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PMID: 

Food Funct. 2019 Jan 22 ;10(1):38-48. PMID: 30548041

Abstract Title: 

Immunostimulatory effect of kumquat (Fortunella crassifolia) and its constituents,β-cryptoxanthin and R-limonene.

Abstract: 

Natural killer (NK) cells play an important role in the innate immune system by eliminating cancer cells and virally infected cells. Aging and stress attenuate the activity of NK cells, thereby increasing the risk of various diseases. In this study, we demonstrated that the consumption of a small number of kumquats in an in vivo model could suppress elevated plasma corticosterone levels and reverse the decline in splenocyte cytotoxicity caused by restraint stress. Our results identifiedβ-cryptoxanthin (BCX) as an active kumquat component with a NK cell-activating effect, and R-limonene as an active component that mediates not only the anti-stress effect but also NK cell activation by oral administration. In addition, BCX, R-limonene, and R-limonene metabolites were found to enhance IFN-γ production in KHYG-1 cells, a human NK cell line. Collectively, our findings suggest that the ingestion of a few kumquats on a daily basis can help to combat stress and enhance NK cell activity.

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PMID: 

EXCLI J. 2019 ;18:405-421. Epub 2019 Jun 17. PMID: 31338010

Abstract Title: 

Immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells.

Abstract: 

Curcuminoids are dietary complexes extracted from the seeds of. that contain curcumin, bisdemethoxycurcumin and desmethoxycurcumin. Curcuminoids are popular for their pleiotropic therapeutic functions, such as their anti-inflammatory and anti-oxidant effects. Nonetheless, their clinical use is associated with poor systemic bioavailability and insolubility. The nano-formulation of curcuminoids eliminates these shortcomings. In the present study, we explored immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells (AT-MSCs). Flow cytometry analysis and MTT assay were employed to explore the effects of nanocurcuminoids on the apoptosis and proliferation of adipose-derived MSCs (AT-MSCs). The anti-oxidant effect of nanocurcuminoids on AT-MSCs also was examined. The immune regulatory effect of nanocurcuminoids was evaluated by the flow cytometric measurement of the T regulatory (Treg) population. The expression of inflammatory and anti-inflammatory cytokines was quantified using real-time PCR. Our findings demonstrate that low concentrations of nanocurcuminoids are beneficial for MSC proliferation, protection of MSCs from apoptosis, reducing inflammatory cytokines and SOD activity. A high concentration of nanocurcuminoids increases the population of Tregs and elevates the expression of TGFβ and FOXP3 genes. The beneficial effects of nanocurcuminoids on AT-MSCs were mainly observed at low doses of nanocurcuminoids.

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PMID: 

Int J Mol Sci. 2019 Sep 28 ;20(19). Epub 2019 Sep 28. PMID: 31569415

Abstract Title: 

Curcumin Mitigates Immune-Induced Epithelial Barrier Dysfunction by.

Abstract: 

() is the most common cause of foodborne gastroenteritis worldwide. The bacteria induce diarrhea and inflammation by invading the intestinal epithelium. Curcumin is a natural polyphenol from turmeric rhizome of, a medical plant, and is commonly used in curry powder. The aim of this study was the investigation of the protective effects of curcumin against immune-induced epithelial barrier dysfunction ininfection. The indirect-induced barrier defects and its protection by curcumin were analyzed in co-cultures with HT-29/B6-GR/MR epithelial cells together with differentiated THP-1 immune cells. Electrophysiological measurements revealed a reduction in transepithelial electrical resistance (TER) in infected co-cultures. An increase in fluorescein (332 Da) permeability in co-cultures as well as in the germ-free IL-10mouse model afterinfection was shown. Curcumin treatment attenuated the-induced increase in fluorescein permeability in both models. Moreover, apoptosis induction, tight junction redistribution, and an increased inflammatory response-represented by TNF-α, IL-1β, and IL-6 secretion-was observed in co-cultures after infection and reversed by curcumin. In conclusion, curcumin protects against indirect-triggered immune-induced barrier defects and might be a therapeutic and protective agent in patients.

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PMID: 

Int J Dent. 2020 ;2020:4706418. Epub 2020 Mar 21. PMID: 32273893

Abstract Title: 

Rinsing with L-Ascorbic Acid Exhibits Concentration-Dependent Effects on Human Gingival Fibroblast In Vitro Wound Healing Behavior.

Abstract: 

Vitamin C or L-ascorbic acid has diverse functions in the body, especially healing promotion in tissue injury via participating in the hydroxylation reactions required for collagen formation. Systemic administration of vitamin C plays an important role on gingival fibroblast proliferation and functions. Whether local or rinsing administration of vitamin C alters gingival fibroblast wound healing behavior remains unclear. The aim of this study was to investigate the rinsing effect of vitamin C on gingival fibroblast behavior utilizing anwound healing model. Primary human gingival fibroblasts isolated from gingival tissue were rinsed with medium containing various concentrations of vitamin C. The rinsing effect of vitamin C on in vitro wound healing was assessed using a scratch test assay. Cell migration, cell viability, and extracellular matrix gene expression were analyzed by transwell migration assay, MTT assay, and real-time RT-PCR, respectively. We found that rinsing with 10 or 20 g/ml vitamin C significantly increased fibroblast migration (≤ 0.05). However, no significant effect was found in the cell viability or in vitro wound healing assays. In contrast, rinsing with 50 g/ml vitamin C significantly delayed wound closure (≤ 0.05). Real-time PCR demonstrated that 50 g/ml vitamin C significantly increased fibroblast expression of COL1, FN, IL-6, and bFGF. The data demonstrate that rinsing with vitamin C (10/20 g/ml) accelerates fibroblast migration. However, 50 g/ml of vitamin C increases the expression of COL1, FN, IL-6, and bFGF, which are related to fibroblast wound healing activity. Prescribing vitamin C with the appropriate duration and drug administration method should be determined to maximize its benefit.

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