PMID: 

J Am Coll Nutr. 2011 Aug ;30(4):248-58. PMID: 21917705

Abstract Title: 

Dietary intake and supplement use of vitamins C and E and upper respiratory tract infection.

Abstract: 

OBJECTIVE: Antioxidants are regulators of immune function and may play a role in upper respiratory tract infections (URTI). We investigated the potential effects of dietary intake from food and supplement use of vitamins C and E on the risk of self-reported URTI.METHODS: We conducted a population-based cohort study of 1509 Swedish men and women ages 20 to 60 with a follow-up period of 4 months. Participants reported a total of 1181 occurrences of URTI. Poisson regression model was used to control for age, sex, and other confounding factors.RESULTS: Among women, we found that the incidence rate ratio (IRR) for high intake of vitamin C (>200 mg/d) from food was 0.69 (95% CI 0.49-0.98) compared with low intake (150 mg/d) compared with low intake (

read more

PMID: 

J Ayub Med Coll Abbottabad. 2012 Jul-Dec;24(3-4):31-5. PMID: 24669603

Abstract Title: 

Effect of ascorbic acid and alpha tocopherol on immune status of male Sprague Dawley rats exposed to chronic restraint stress.

Abstract: 

BACKGROUND: The immune system provides protection against infectious diseases or other insults. Psychological stress may alter antibody production through neurobiological pathways. Antioxidant supplementation is thought to improve immune status and thereby reduce infectious morbidity. The aim of this study was to determine the preventive effect of ascorbic acid and alpha tocopherol on immune status of rats exposed to chronic restraint stress.METHODS: A total of 150 healthy male Sprague Dawley rats were included in the study. They were divided into 5 groups, each comprised of 30 rats. Group I was the control group on normal diet. Group II rats were exposed to chronic restraint stress for 6 hours daily for 15 days, without antioxidant supplementation, whereas rats of groups III, IV and V were given supplementation of ascorbic acid or alpha tocopherol or both respectively, for one month prior to exposure of rats to chronic restraint stress. Total leukocyte count (TLC) and lymphocyte counts was done, and serum immuno-globulins (IgG, IgA, IgM, and IgE) levels were estimated using ELISA.RESULTS: Total leukocyte and lymphocyte counts and serum IgA, IgE, IgG, and IgM levels were found significantly (p 0.001) decreased in rats exposed to chronic restraint stress compared to the rats not exposed to the restraint stress. The combined supplementation of ascorbic acid and alpha tocopherol significantly (p 0.001) prevented the decline in total leukocyte and lymphocyte counts and serum immuno-globulins compared to the administration of either of the two antioxidants.CONCLUSION: Antioxidants (ascorbic acid and alpha tocopherol) given in combination produce greater beneficial effect in improving the immune status of rats exposed to chronic stress than individual supplementation of either ascorbic acid or alpha tocopherol.

read more

PMID: 

Cell Mol Biol (Noisy-le-grand). 2012 May 15 ;58 Suppl:OL1688-94. Epub 2012 May 15. PMID: 22762523

Abstract Title: 

Effect of interaction of vitamin C on macrophage immune response to infection with Mycobacterium bovis.

Abstract: 

Bovine tuberculosis is a chronic infectious disease caused by Mycobacterium bovis affecting humans and livestock. Like Mycobacterium tuberculosis (M.tb), M. bovis can persist in cattle without causing overt symptoms after entering a non-replicating persistent (NRP) state. Given that M.tb enters NRP under stress conditions, we sought to find the effects of vitamin C (VC) on M. bovis in vitro and in vivo (VC could mimic stresses like hypoxia by O2 scavenging and acidic conditions in phagosome). M. bovis was cultured in a medium with VC for 48 h. The differential expression of five genes (dosR, dosS, dosT, icl, and hspX of M. bovis) implicated in the M. bovis NRP state was measured with real-time quantitative PCR. Expression of all five genes was increased by VC. Relative to the control, VC-exposed bacteria appeared smaller and more rounded in shape with a much thicker inner envelope. A lower number of viable bacteria were found in comparison with those of the control. We infected macrophage cell line ANA-1 with M. bovis and cultured it in VC-added medium (MC group) for 24h and 48 h. Expression of il-10, il-6, tnf-α, and il-β was examined and compared with expression by cells infected by M. bovis only without VC treatment (MB group), uninfected cells in the medium treated with VC (VC group), and cells in the medium only without VC. Il-1β, tnf-α, and il-6 transcription were up-regulated significantly in MCgroup. IL-10 gene expression in MB and MC groups was less than in the control at 24h, but that of MC group increased more than the MB group at 48 h. The numbers of intracellular M. bovis in the MC group were lower than that in the other groups. Slower growth was found in VC-treated M. bovis, and macrophages were more bactericidal for intracellular VC-stimulated M. bovis than for M. bovis with no VC treatment.

read more

PMID: 

Antioxid Redox Signal. 2013 Dec 10 ;19(17):2054-67. Epub 2013 Feb 5. PMID: 23249337

Abstract Title: 

Vitamin C promotes maturation of T-cells.

Abstract: 

AIMS: Vitamin C (ascorbic acid) is thought to enhance immune function, but the mechanisms involved are obscure. We utilized an in vitro model of T-cell maturation to evaluate the role of ascorbic acid in lymphocyte development.RESULTS: Ascorbic acid was essential for the developmental progression of mouse bone marrow-derived progenitor cells to functional T-lymphocytes in vitro and also played a role in vivo. Ascorbate-mediated enhancement of T-cell development was lymphoid cell-intrinsic and independent of T-cell receptor (TCR) rearrangement. Analysis of TCR rearrangements demonstrated that ascorbic acid enhanced the selection of functional TCRαβ after the stage of β-selection. Genes encoding the coreceptor CD8 as well as the kinase ZAP70 were upregulated by ascorbic acid. Pharmacologic inhibition of methylation marks on DNA and histones enhanced ascorbate-mediated differentiation, suggesting an epigenetic mechanism of Cd8 gene regulation via active demethylation by ascorbate-dependent Fe(2+) and 2-oxoglutarate-dependent dioxygenases.INNOVATION: We speculate that one aspect of gene regulation mediated by ascorbate occurs at the level of chromatin demethylation, mediated by Jumonji C (JmjC) domain enzymes that are known to be reliant upon ascorbate as a cofactor. JmjC domain enzymes are also known to regulate transcription factor activity. These two mechanisms are likely to play key roles in the modulation of immune development and function by ascorbic acid.CONCLUSION: Our results provide strong experimental evidence supporting a role for ascorbic acid in T-cell maturation as well as insight into the mechanism of ascorbate-mediated enhancement of immune function.

read more

PMID: 

Neurobiol Dis. 2019 07 ;127:432-448. Epub 2019 Apr 2. PMID: 30951849

Abstract Title: 

Curcumin restores innate immune Alzheimer's disease risk gene expression to ameliorate Alzheimer pathogenesis.

Abstract: 

Alzheimer's disease (AD) genetics implies a causal role for innate immune genes, TREM2 and CD33, products that oppose each other in the downstream Syk tyrosine kinase pathway, activating microglial phagocytosis of amyloid (Aβ). We report effects of low (Curc-lo) and high (Curc-hi) doses of curcumin on neuroinflammation in APPsw transgenic mice. Results showed that Curc-lo decreased CD33 and increased TREM2 expression (predicted to decrease AD risk) and also increased TyroBP, which controls a neuroinflammatory gene network implicated in AD as well as phagocytosis markers CD68 and Arg1. Curc-lo coordinately restored tightly correlated relationships between these genes' expression levels, and decreased expression of genes characteristic of toxic pro-inflammatory M1 microglia (CD11b, iNOS, COX-2, IL1β). In contrast, very high dose curcumin did not show these effects, failed to clear amyloid plaques, and dysregulated gene expression relationships. Curc-lo stimulated microglial migration to and phagocytosis of amyloid plaques both in vivo and in ex vivo assays of sections of human AD brain and of mouse brain. Curcumin also reduced levels of miR-155, a micro-RNA reported to drive a neurodegenerative microglial phenotype. In conditions without amyloid (human microglial cells in vitro, aged wild-type mice), Curc-lo similarly decreased CD33 and increased TREM2. Like curcumin, anti-Aβ antibody (also reportedto engage the Syk pathway, increase CD68, and decrease amyloid burden in human and mouse brain) increased TREM2 in APPsw mice and decreased amyloid in human AD sections ex vivo. We conclude that curcumin is an immunomodulatory treatment capable of emulating anti-Aβ vaccine in stimulating phagocyticclearance of amyloid by reducing CD33 and increasing TREM2 and TyroBP, while restoring neuroinflammatory networks implicated in neurodegenerative diseases.

read more

PMID: 

Inflammopharmacology. 2019 Oct ;27(5):885-900. Epub 2019 May 28. PMID: 31140036

Abstract Title: 

Curcumin: a modulator of inflammatory signaling pathways in the immune system.

Abstract: 

Curcumin is a natural compound derived from the spice, turmeric, that has been extensively reported for its efficacy in controlling or treatment of several inflammatory diseases. There is a growing body of literature that recognizes the anti-inflammatory effects of curcumin in the immune system. On the other hand, the role of inflammatory signaling pathways has been highlighted in the pathogenesis of several inflammatory diseases, and signaling molecules involved in these pathways are considered as valuable targets for new treatment approaches. We aimed to provide a comprehensive overview of the modulatory effects of curcumin on inflammatory signaling pathways which leads to inhibition of inflammation in different types of immune cells and animal models. In this comprehensive review, we elaborate on how curcumin can effectively inhibit multiple signaling molecules involved in inflammation including NF-κB, JAKs/STATs, MAPKs, β-catenin, and Notch-1.

read more

PMID: 

Infect Drug Resist. 2019 ;12:1833-1852. Epub 2019 Jul 1. PMID: 31303775

Abstract Title: 

Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies.

Abstract: 

There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue.To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection.Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely.DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%,

read more

PMID: 

Phytother Res. 2019 Nov ;33(11):2798-2820. Epub 2019 Aug 19. PMID: 31429161

Abstract Title: 

Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies.

Abstract: 

Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti-inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English-language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis-induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.

read more

PMID: 

Endocr Metab Immune Disord Drug Targets. 2019 Aug 23. Epub 2019 Aug 23. PMID: 31441735

Abstract Title: 

Curcumin Suppresses Epithelial Growth Factor Receptor (EGFR) and Proliferative Protein (Ki 67) in Acute Lung Injury and Lung Fibrosis In Vitro and In Vivo.

Abstract: 

BACKGROUND: Acute lung injury is one of the common condition caused due to bleomycin therapy which leads to pulmonary fibrosis, which is one of the severe interstitial lung disease most commonly affecting the elderly individuals. EGFR and Ki67 are can be marked as beneficial markers for detecting pulmonary fibrosis based on which clinicians can guide therapy.OBJECTIVE: The aim of the study was to evaluate effect of curcumin as an intervention on two prognostic markers EGFR and Ki67 in bleomycin induced basal alveolar epithelial cells and C57BL/6 mice. Protein expressions and pathological expressions of EGFR and Ki67 were evaluated to analyze the effect of curcumin on it both in in vitro and in vivo approaches.METHODS: The effect of curcumin was investigated both on cell lines (A549) and animal model (both normal and bleomycin induced mice, n=6) via techniques like western blotting for protein expression. Techniques like immunofluorescence and immunohistochemistry was carried out and examined under confocal microscopy and phase contrast microscope to analyze the expressions of the said biomarkers. Bleomycin was used as a causative agent to induce inflammation.KEY FINDINGS: The natural polyphenol curcumin could downregulate the expressions levels of Ki67 and EGFR both in vitro and in vivo. Immunofluorescence analysis on proliferative marker Ki67 showed reduced expression on curcumin treatment in vitro. The pathological sections from treated lungs showed significant decrease in EGFR and Ki67 levels when exposed to curcumin.CONCLUSION: We conclude that curcumin, well-known natural bioactive compound holds strong anti-proliferative on Ki67 and EGFR expressions.We observed that, a clinical outcome in diagnosis of pulmonary fibrosis remains to be unconvincing so far. Curcumin can be considered as a potential therapeutic.

read more

PMID: 

Immune Netw. 2019 Oct ;19(5):e35. Epub 2019 Oct 17. PMID: 31720046

Abstract Title: 

Curcumin Elevates TCells and Germinal Center B Cell Response for Antibody Production in Mice.

Abstract: 

Curcumin is a natural product extracted from. It has been reported as a potent antioxidant and anti-inflammatory compound. Previous studies have demonstrated that curcumin suppresses pro-inflammatory cytokine production via inhibition of NF-κB in macrophages. However, its role in adaptive immune cells such as T cells,, has not clearly been elucidated. Here, we examined the effects of curcumin in T follicular helper (T) cells and on Ab production during NP-ovalbumin immunization in mice. The results revealed that curcumin administered daily significantly increased CXCR5B-cell lymphoma 6Tcells and CD95GL-7germinal center (GC) B cells in draining lymph nodes. In addition, curcumin treatment in mice induced total Ab production as well as high affinity IgG1 and IgG2b Ab production. Collectively, these results suggest that curcumin has positive regulatory roles in Tcell functions and GC responses. Thus, this could be an advantageous supplement to enhance humoral immunity against infectious diseases and cancer.

read more