PMID: 

J Neuroimmunol. 2018 11 15 ;324:54-75. Epub 2018 Sep 12. PMID: 30243185

Abstract Title: 

Therapeutic potentials of ginger for treatment of Multiple sclerosis: A review with emphasis on its immunomodulatory, anti-inflammatory and anti-oxidative properties.

Abstract: 

Multiple sclerosis (MS) is characterized by chronic inflammatory response-induced demyelination of the neurons and degeneration of the axons within the central nervous system (CNS). A complex network of immunopathological-, inflammatory- and oxidative parameters involve in the development and advancement of MS. The anti-inflammatory, immunomodulatory and anti-oxidative characteristics of the ginger and several of its components have been indicated in some of experimental and clinical investigations. The possible therapeutic potentials of ginger and its ingredients in the treatment of MS may exert mainly through the regulation of the Th1-, Th2-, Th9-, Th17-, Th22- and Treg cell-related immune responses, down-regulation of the B cell-related immune responses, modulation of the macrophages-related responses, modulation of the production of pro- and anti-inflammatory cytokines, down-regulation of the arachidonic acid-derived mediators, interfering with the toll like receptor-related signaling pathways, suppression of the inflammasomes, down-regulation of the oxidative stress, reduction of the adhesion molecules expression, and down-regulation of the expression of the chemokines and chemokine receptors. This review aimed to provide a comprehensive knowledge regarding the immunomodulatory-, anti-inflammatory and anti-oxidative properties of ginger and its components, and highlight novel insights into the possible therapeutic potentials of this plant for treatment of MS. The review encourages more investigations to consider the therapeutic potentials of ginger and its effective components for managing of MS.

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PMID: 

J Microbiol Biotechnol. 2019 Jul 28 ;29(7):1053-1060. PMID: 31280523

Abstract Title: 

Effect of Differential Thermal Drying Conditions on the Immunomodulatory Function of Ginger.

Abstract: 

Thermal drying is a common process used in the food industry for the modification of agricultural products. However, while various studies have investigated the alteration in physiochemical properties and chemical composition after drying, research focusing on the relationship between different dehydration conditions and bioactivity is scarce. In the current study, we prepared dried ginger under nine different conditions by varying the processing time and temperature and compared their immunomodulatory effects. Interestingly, depending on the drying condition, there were significant differences in the immunestimulating activity of the dried ginger samples. Gingers processed at 50°C 1h displayed the strongest activation of macrophages measured by TNF-α and IL-6 levels, whereas, freezedried or 70°C- and 90°C-dried ginger showed little effect. Similar results were recapitulated in primary bone marrow-derived macrophages, further confirming that different dehydration conditions can cause significant differences in the immune-stimulating activity of ginger. Induction of ERK, p38, and JNK signaling was found to be the major underlying molecular mechanism responsible for the immunomodulatory effect of ginger. These results highlight the potential to improve the bioactivity of functional foods by selectively controlling processing conditions.

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PMID: 

Biochem Biophys Res Commun. 2020 Mar 19. Epub 2020 Mar 19. PMID: 32201078

Abstract Title: 

Echinacoside inhibits breast cancer cells by suppressing the Wnt/β-catenin signaling pathway.

Abstract: 

Echinacoside, a small molecule derived from the natural herbs Cistanche and Echinacea, shows effective anticancer abilities, but the mechanism remains unclear. By using colony formation, scratch, and transwell assays in MDA-MB-231 breast cancer cells, we confirmed the anti-breast cancer ability of Echinacoside in vitro. In addition, we found that Echinacoside can dose-dependently reduce phosho-LRP6, total LRP6, phosho-Dvl2, active β-catenin, and total β-catenin protein expression level in MDA-MB-231 and MDA-MB-468 cells by western blot. We also detected well-known Wnt targets genes, including LEF1, CD44, and cyclin D1 by real-time PCR and western blot, and Echinacoside significantly shows inhibition effect in these two breast cancer cell lines. Furthermore, we investigated its anti-breast cancer ability in an MDA-MB-231 xenograft model in vivo. Echinacoside treatment significantly reduced tumor growth, which was accompanied by a reduction in Wnt/β-catenin signaling. In summary, our results demonstrate that Echinacoside can effectively inhibit Wnt/β-catenin signaling, and therefore, it may be a promising therapeutic target to treat breast cancer.

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PMID: 

Cancers (Basel). 2020 Mar 13 ;12(3). Epub 2020 Mar 13. PMID: 32183059

Abstract Title: 

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells.

Abstract: 

Cancer-related deaths are approaching 10 million each year. Survival statistics for some cancers, such as ovarian cancer, have remained unchanged for decades, with women diagnosed at stage III or IV having over 80% chance of a lethal cancer recurrence after standard first-line treatment (reductive surgery and chemotherapy). New treatments and adjunct therapies are needed. In ovarian cancer, as in other cancers, the immune response, particularly cytotoxic (CD8) T cells are correlated with a decreased risk of recurrence. As well as completely new antigen targets resulting from DNA mutations (neo-antigens), these T cells recognize cancer-associated overexpressed, re-expressed or modified self-proteins. However, there is concern that activation of self-reactive responses may also promote off-target pathology. This review considers the complex interplay between cancer-reactive and self-reactive immune cells and discusses the potential uses for various leading immunomodulatory compounds, derived from plant-based sources, as a cancer therapy option or to modulate potential autoimmune pathology. Along with reviewing well-studied compounds such as curcumin (from turmeric), epigallocatechin gallate (EGCG, from green tea) and resveratrol (from grapes and certain berries), it is proposed that compounds from novel sources, for example, native Australian plants, will provide a useful source for the fine modulation of cancer immunity in patients.

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PMID: 

Am J Med Sci. 2018 10 ;356(4):350-356. PMID: 30360803

Abstract Title: 

Use of Curcumin in Achieving Clinical and Endoscopic Remission in Ulcerative Colitis: A Systematic Review and Meta-analysis.

Abstract: 

BACKGROUND: Ulcerative Colitis (UC) is characterized by chronic inflammation of the mucosal layers of the colon. Treatment of refractory UC is challenging and has a huge healthcare burden. Although there have been advancements in immunomodulatory therapies, these require a step-up financially, and these medications are also associated with significant adverse events. Curcumin, an active ingredient of turmeric, has been studied in the past and found to be useful in the treatment of UC when used as an adjuvant along with mesalamine. We did a systematic review and meta-analysis to explore the role curcumin plays in clinical and endoscopic remission in patients with UC.MATERIALS AND METHODS: A comprehensive literature review was conducted by first searching the MEDLINE, Pubmed, and Embase databases through December 2017 to identify all studies that compared the use of curcumin when used along with mesalamine with placebo for clinical and endoscopic improvement and remission.RESULTS: Three randomized controlled trials including 142 patients were included in the study. Use of curcumin along with mesalamine was associated with increased odds of clinical remission (pooled odds ratio of 6.78, 95% CI: 2.39-19.23, P = 0.042). Clinical improvement, endoscopic remission and improvement rate also trended higher in the curcumin group compared to placebo.CONCLUSIONS: This study demonstrates higher clinical remission rates when curcumin was used in combination with mesalamine to achieve remission in patients with UC. Curcumin, due to its cost effectiveness and safer side effect profile, can decrease the healthcare burden and morbidity associated with this relapsing and remitting disease.

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PMID: 

Reprod Domest Anim. 2019 Jun ;54(6):917-923. Epub 2019 May 10. PMID: 30972855

Abstract Title: 

Immunomodulatory effect of curcumin on lipopolysaccharide- and/or flagellin-induced production of prostaglandin E2 and relative expression of proinflammatory cytokines in the primary bubaline endometrial stromal cells.

Abstract: 

Developing alternate therapies for bovine endometritis is important in the context of drug residues in the milk and emergence of antimicrobial resistant bacteria. In this regard, we studied the immunomodulatory effect of curcumin 30 µM, on lipopolysaccharide- (LPS) and/or flagellin (100 ng/ml each)-induced prostaglandin E(PGE) and proinflammatory cytokines (PIC) using primary bubaline endometrial stromal cells. After 24 hr treatment, the supernatant was assayed for PGEwhile cells were used for relative quantification of cytokines like IL-1β, IL-6, IL-8 and TNF α transcripts using a control group as calibrator. LPS was found to possess potent stimulatory effect on PGEproduction, whereas the flagellin was not as potent as LPS in stimulating the PGEproduction either per se or in combination with LPS. LPS markedly up-regulated the transcripts of IL-8 and IL-6 as compared to IL-1β and TNF α in the bubaline endometrial stromal cells. Except for IL-8, flagellin did not up-regulate other PICs. There was no additive effect between LPS and flagellin on the up-regulation of inflammatory cytokines. Curcumin inhibited the LPS-induced up-regulation of PIC with strong down-regulation of IL-8. The inhibitory effects of curcumin on the inflammatory mediators suggest a potential in the treatment of bovine endometritis.

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The Bill and Melinda Gates Foundation has donated more than $21 million towards developing a vaccine technology that uses a tattoo-like mechanism.

PMID: 

Inflammation. 2019 Dec ;42(6):2037-2047. PMID: 31407145

Abstract Title: 

Immunomodulatory and Anti-Inflammatory Potential of Curcumin for the Treatment of Allergic Asthma: Effects on Expression Levels of Pro-inflammatory Cytokines and Aquaporins.

Abstract: 

Curcumin is well known for possessing anti-inflammatory properties and for its beneficial effects in the treatment of asthma. Current study investigates the immunomodulatory and anti-inflammatory effects of curcumin using mouse model of ovalbumin-induced allergic asthma. BALB/c mice were immunized with ovalbumin on day 0 and 14 to induce allergic asthma. Animals were treated with two different doses of curcumin (20 mg/kg and 100 mg/kg) and methylprednisolone from day 21 to 28. Mice were also daily challenged intranasally with ovalbumin during treatment period, and all groups were sacrificed at day 28. Histopathological examination showed amelioration of allergic asthma in treated groups as evident by the attenuation of infiltration of inflammatory cells, goblet cell hyperplasia, alveolar thickening, and edema and vascular congestion. Curcumin significantly reduced total and differential leukocyte counts in both bronchoalveolar lavage fluid and blood. Reverse transcription polymerase chain reaction analysis showed significantly suppressed mRNA expression levels of IL-4 and IL-5 (pro-inflammatory cytokines), TNF-α, TGF-β (pro-fibrotic cytokines), eotaxin (chemokine), and heat shock protein 70 (marker of airway obstruction) in treated groups. Attenuation of these pro-inflammatory markers might have led to the suppression of airway inflammation. The expression levels of aquaporin-1 (AQP) and AQP-5 were found significantly elevated in experimental groups which might be responsible for reduction of pulmonary edema. In conclusion, curcumin significantly ameliorated allergic asthma. The anti-asthmatic effect might be attributed to the suppression of pro-inflammatory cytokines, and elevation of aquaporin expression levels, suggesting further studies and clinical trials to establish its candidature in the treatment of allergic asthma.

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PMID: 

Environ Sci Pollut Res Int. 2020 Apr ;27(10):10950-10965. Epub 2020 Jan 17. PMID: 31953765

Abstract Title: 

Ameliorative effect of curcumin against lead acetate-induced hemato-biochemical alterations, hepatotoxicity, and testicular oxidative damage in rats.

Abstract: 

Lead, toxic heavy metal of global concern, induces toxicity in various organs via oxidative stress. Thereby, in this study, the protective role of curcumin against lead acetate-induced toxicity was evaluated. Thirty-two male albino rats were allocated equally into four groups and orally administered with corn oil as a vehicle (Cont.), curcumin (CUR) (400 mg/kg bw), lead acetate (LA) (100 mg/kg bw), and lead acetate plus curcumin (LA + CUR). All rats had received their treatments daily for 4 weeks. The results revealed that LA toxicity induced normocytic normochromic anemia with significant leukocytosis and lymphocytosis. Moreover, LA-intoxicated rats showed a marked elevation in the liver enzyme activities, serum cholesterol, and triglyceride levels. In contrast, sero-immunological parameters, total protein, albumin, globulin, and testosterone levels were significantly reduced compared to the control rats. Additionally, LA-induced hepatic and testicular oxidative damage revealed by marked increased in MDA level with prominent reduction in the antioxidant system. The gene expression of the hepatic pro-inflammatory markers and testicular steroidogenic biomarkers including LHR and aromatase were significantly upregulated; meanwhile,the expressions of testicular StAR, CYP17a, 3B-HDS, SR-B1, and P450SCC were significantly downregulated in the LA-intoxicated group. Curcumin treatment could partially improve the hematological, biochemical, and histopathological alterations induced by LA. Also, it was observed that curcumin significantly restored hepatic pro-inflammatory markers and testicular steroidogenic enzymes. In conclusion, curcumin has antioxidant, anti-inflammatory, and immunomodulatory effects and is able to minimize the LA-induced oxidative damage in rats.

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PMID: 

Recent Pat Inflamm Allergy Drug Discov. 2019 ;13(2):84-104. PMID: 31814545

Abstract Title: 

Effects of Flavonoids and Its Derivatives on Immune Cell Responses.

Abstract: 

BACKGROUND: Various pieces of evidence have shown that people who consume foods rich in polyphenolic and flavonoids compounds have a lower incidence of inflammatory, autoimmune diseases and cancer.OBJECTIVE: The study aimed to review the most potent compounds that affect the immune response and diseases associated with it.METHODS: Publications in PubMed and EmBase, from 1974-2018, and patents form Free patents online, Scifinder, Espacenet and Mendeley in which flavonoids, their semi-synthetic and synthetic derivatives are involved in immunosuppressive or immunostimulatory responses in vitro and in vivo.RESULTS: In vitro, flavonoids and their derivatives inhibit various transcriptional factors, which modulate differentiation, proliferation, activation of immune cells and enhance regulatory T cell generation. Some flavonoids exert anti-inflammatory effects through: Blockade of NF-κB, and NLRP3 inflammasome, inhibition of pro-inflammatory cytokine production, IL-1β, IL-2, IL-6, TNF-α, IL-17A, down regulation of chemokines, and reduction of reactive oxygen and nitrogen species. Nevertheless, several reports have shown that some flavonoids enhance immune response by enhancing: oxygen and nitrogen radicals, antibody production, cytotoxic activity against tumours by increasing activating receptors and down regulating inhibitory receptors. In consequence, flavonoids may be potentially useful for treatment of infectious diseases and cancer.CONCLUSION: The most potent flavonoids in inflammation that modify immune responses are apigenin, quercetin and Epigallocatechin-3-Gallate (EGCG) although, other compounds are still under study and cannot be excluded. The most relevant patents concerning the use of flavones and other polyphenols were revised. A promising future of these compounds in different therapies is discussed.

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