PMID: 

Anticancer Agents Med Chem. 2020 Mar 10. Epub 2020 Mar 10. PMID: 32160852

Abstract Title: 

Urtica dioica Extract Inhibits Cell Proliferation and Induces Apoptosis in HepG2 and HTC116 as Gastrointestinal Cancer Cell Lines.

Abstract: 

BACKGROUND: Nowadays the use of plant-derived products has been extensively examined in the treatment of many types of gastrointestinal cancer such as hepatocarcinoma and colon cancer. Urtica dioica is a traditional herb that has many pharmacological effects and wildly used as a therapeutic agent in cancer. Herein, we have evaluated the effects of the different concentrations of Methanolic Extract of Urtica dioica (MEUD) on viability, death pattern, and expression of the apoptosis-related gene in normal Human Dermal Fibroblast (HDF), hepatocarcinoma cell lines (HepG2) and colon-cancer cell line (HCT116).METHODS: A high-performance liquid chromatography method was developed to simultaneously separate 3 phenolic acids in MEUD. HepG2 and HCT116 cell lines as well as HDF normal cell line were cultured in suitable media. After 24 and 48h, cultured cell with different concentrations of MEUD, Cells viability was assessed by MTT assay, and apoptosis was also evaluated at the cellular level by Annexin V/PI flowcytometry analyzing and AO/EB staining. BCL2 and BAX gene expression were assessed by TaqMan real-time PCR assay.RESULTS: MEUD showed antiproliferative effects on HepG2 and HTC116 cells after 48h with an IC50 value of about 410 and 420μg/ml, respectively (P

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PMID: 

Phytochem Anal. 2014 Mar-Apr;25(2):147-54. Epub 2014 Jan 10. PMID: 24408862

Abstract Title: 

Identification and anti-oxidant capacity determination of phenolics and their glycosides in elderflower by on-line HPLC-CUPRAC method.

Abstract: 

INTRODUCTION: Development and application of an on-line cupric reducing anti-oxidant capacity (CUPRAC) assay coupled with HPLC for separation and on-line determination of phenolic anti-oxidants in elderflower (Sambucus nigra L.) extracts for their anti-oxidant capacity are significant for evaluating health-beneficial effects. Moreover, this work aimed to assay certain flavonoid glycosides of elderflower that could not be identified/quantified by other similar on-line HPLC methods (i.e. 2,2-diphenyl-1-picrylhdrazyl and 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid).OBJECTIVE: To identify anti-oxidant constituents in elderflower by HPLC and to evaluate their individual anti-oxidant capacities by on-line HPLC-CUPRAC assay with a post-column derivatisation system.METHODS: The separation and UV detection of polyphenols were performed on a C18 -column using gradient elution with two different mobile phase solutions, that is acetonitrile and 1% glacial acetic acid, with detection at 340 nm. The HPLC-separated anti-oxidant polyphenols in column effluent react with copper(II)-neocuproine in a reaction-coil to reduce the latter to copper(I)-neocuproine (Cu(I)-Nc) chelate having maximum absorption at 450 nm.RESULTS: The detection limits of tested compounds at 450 nm after post-column derivatisation were compared with those of at 340 nm UV-detection without derivatisation. LOD values (µg/mL) of quercetin and its glycosides at 450 nm were lower than those of UV detection at 340 nm. This method was applied successfully to elderflower extract. The flavonol glycosides of quercetin and kaempferol bound to several sugar components (glucose, rhamnose, galactose and rutinose) were identified in the sample.CONCLUSION: The on-line HPLC-CUPRAC method was advantageous over on-line ABTS and DPPH methods for measuring the flavonoid glycosides of elderflower.

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PMID: 

J Diet Suppl. 2014 Mar ;11(1):80-120. Epub 2014 Jan 10. PMID: 24409980

Abstract Title: 

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration.

Abstract: 

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

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PMID: 

Chin J Nat Med. 2020 Feb ;18(2):103-113. PMID: 32172946

Abstract Title: 

Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway.

Abstract: 

We investigated the liver protective activity of dandelion polyphenols (DP) against acetaminophen (APAP; Paracetamol)-induced hepatotoxicity. Mice were acclimated for 1 week and randomly divided into the following groups (n = 9 per group): Control, APAP, APAP + DP (100 mg·kg), APAP + DP (200 mg·kg), and APAP + DP (400 mg·kg) groups. Mice were pretreated with DP (100, 200, and 400 mg·kg) by oral gavage for 7 d before being treated with 350 mg·kgAPAP for 24 h to induced hepatotoxicity. Severe liver injury was observed, and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers, protein expressions levels, and liver histopathology. Pretreatment with DP was able to restore serum liver characteristics (aspartate transaminase, AST; alanine aminotransferase, ALT; alkaline phosphatase, AKP), improve redox imbalance (superoxide dismutase, SOD; glutathione, GSH; malondialdehyde, MDA), and decrease inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β). Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein. DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1. The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration, congestion, and necrosis. Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

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PMID: 

Int J Mol Sci. 2013 Jun 6 ;14(6):12205-21. Epub 2013 Jun 6. PMID: 23743830

Abstract Title: 

Enhancement of immune activation activities of Spirulina maxima grown in deep-sea water.

Abstract: 

In this study, the immuno-modulatory and anticancer activities of marine algae, Spirulina maxima grown in deep-sea water (DSW), were investigated. It was found that the extract of S. maxima, cultured in DSW, effectively suppressed the expression of Bcl2 in A549 cells as well as inhibiting various human cancer cells with concentration dependency, which possibly implies that the extracts may play more important roles in controlling cancer cell growth. The secretion of cytokines IL-6 and TNF-α from human B cells was also greatly increased, compared to those of the extract grown in conventional sea-water. The growth of Human Natural Killer (NK) cells in the presence of the extracts from DSW was significantly higher (12.2 × 104 viable cells/mL) when compared to the control (1.1 × 104 viable cells/mL). Based on HPLC analysis, the increase in the biological activities of the extracts from DSW was caused by considerably high amounts of β-carotene and ascorbic acid because the DSW contained high concentrations and good ratios of several key minerals for biosynthesizing β-carotene and ascorbic acid, as well as maintaining high cell growth.

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“A sad soul can kill you quicker than a germ”

– John Steinbeck

Hundreds of millions of adults and children are now either in quarantine in their homes, or engaged in “essential” travel in the public sphere, while maintaining an unnatural distance from one another, because they have been told this is the best way to protect their individual and the public health from a deadly virus. But what are the consequences of the social isolation caused by this mass social distancing experiment? 

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PMID: 

Front Immunol. 2019 ;10:2211. Epub 2019 Sep 13. PMID: 31572402

Abstract Title: 

Vitamin D Signaling in the Context of Innate Immunity: Focus on Human Monocytes.

Abstract: 

The vitamin Dmetabolite 1α,25-dihydroxyvitamin D(1,25(OH)D) activates at sub-nanomolar concentrations the transcription factor vitamin D receptor (VDR). VDR is primarily involved in the control of cellular metabolism but in addition modulates processes important for immunity, such as anti-microbial defense and the induction of T cell tolerance. Monocytes and their differentiated phenotypes, macrophages and dendritic cells, are key cell types of the innate immune system, in which vitamin D signaling was most comprehensively investigatedthe use of next generation sequencing technologies. These investigations provided genome-wide maps illustrating significant effects of 1,25(OH)Don the binding of VDR, the pioneer transcription factors purine-rich box 1 (PU.1) and CCAAT/enhancer binding proteinα (CEBPA) and the chromatin modifier CCCTC-binding factor (CTCF) as well as on chromatin accessibility and histone markers of promoter and enhancer regions, H3K4me3 and H3K27ac. Thus, the epigenome of human monocytes is at multiple levels sensitive to vitamin D. These data served as the basis for the chromatin model of vitamin D signaling, which mechanistically explains the activation of a few hundred primary vitamin D target genes. Comparable epigenome- and transcriptome-wide effects of vitamin D were also described in peripheral blood mononuclear cells isolated from individuals before and after supplementation with a vitamin Dbolus. This review will conclude with the hypothesis that vitamin D modulates the epigenome of immune cells during perturbations by antigens and other immunological challenges suggesting that an optimal vitamin D status may be essential for an effective epigenetic learning process, in particular of the innate immune system.

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PMID: 

Mol Cell Biochem. 2020 Jan ;464(1-2):169-180. Epub 2019 Nov 22. PMID: 31758375

Abstract Title: 

Effect of high doses of vitamin D supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles on dendritic cells.

Abstract: 

Dengue, caused by dengue virus (DENV) infection, is a public health problem worldwide. Although DENV pathogenesis has not yet been fully elucidated, the inflammatory response is a hallmark feature in severe DENV infection. Although vitamin D (vitD) can promote the innate immune response against virus infection, no studies have evaluated the effects of vitD on DENV infection, dendritic cells (DCs), and inflammatory response regulation. This study aimed to assess the impact of oral vitD supplementation on DENV-2 infection, Toll-like receptor (TLR) expression, and both pro- and anti-inflammatory cytokine production in monocyte-derived DCs (MDDCs). To accomplish this, 20 healthy donors were randomly divided into two groups and received either 1000 or 4000 international units (IU)/day of vitD for 10 days. During pre- and post-vitD supplementation, peripheral blood samples were taken to obtain MDDCs, which were challenged with DENV-2. We found that MDDCs from donors who received 4000 IU/day of vitD were less susceptible to DENV-2 infection than MDDCs from donors who received 1000 IU/day of vitD. Moreover, these cells showed decreased mRNA expression of TLR3, 7, and 9; downregulation of IL-12/IL-8 production; and increased IL-10 secretion in response to DENV-2 infection. In conclusion, the administration of 4000 IU/day of vitD decreased DENV-2 infection. Our findings support a possiblerole of vitD in improving the innate immune response against DENV. However, further studies are necessary to determine the role of vitD on DENV replication and its innate immune response modulation in MDDCs.

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PMID: 

Vet Res. 2019 Nov 29 ;50(1):101. Epub 2019 Nov 29. PMID: 31783923

Abstract Title: 

Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets.

Abstract: 

Vitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)-infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3-4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrheascores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3-5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively.PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgAβ7(gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets.

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PMID: 

Eur J Nutr. 2014 Apr ;53(3):779-92. Epub 2013 Sep 6. PMID: 24061349

Abstract Title: 

Fucoxanthin in association with vitamin C acts as modulators of human neutrophil function.

Abstract: 

INTRODUCTION: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing and digesting bacteria and fungi. During this process, neutrophils produce reactive oxygen species (ROS), which in excess, can damage the cells themselves and surrounding tissues. The carotenoid fucoxanthin (Fc) has been studied concerning its antioxidant and anti-inflammatory actions. Vitamin c (Vc) also demonstrates potent antioxidant action. This study aimed to evaluate the effect of Fc (2μM) in association with Vc (100 μM) on functional parameters of human neutrophils in vitro.MATERIALS AND METHODS: We evaluated the migration and phagocytic capacity, intracellular calcium mobilization, ROS production (O₂(·)⁻, H₂O₂, HOCl), myeloperoxidase activity, profile of antioxidant enzymes, phosphorylation of p38 MAPK and p65 NFκB subunit, GSH/GSSG ratio and release of pro-inflammatory cytokines (TNF-α and IL-6) in neutrophils under different stimuli.RESULTS: We verified an increase in phagocytic capacity for all treatments, together with an increase in intracellular calcium only in cells treated with Fc and Fc + Vc. ROS production was reduced by all treatments, although Vc was a better antioxidant than Fc. Phosphorylation of the p-65 subunit of NFκB was reduced in cells treated with Fc + Vc and release of TNF-α and IL-6 was reduced by all treatments. These findings indicate that the regulation of inflammatory cytokines by neutrophils is not exclusively under the control of the NFκB pathway. Fc reduced the activity of some antioxidant enzymes, whereas Vc increased GR activity and the GSH/GSSG ratio.CONCLUSION: In conclusion, the results presented in this study clearly show an immunomodulatory effect of the carotenoid fc alone or in combination with Vc on the function of human neutrophils.

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