PMID: 

J Pharm Biomed Anal. 2019 Aug 19 ;177:112820. Epub 2019 Aug 19. PMID: 31476432

Abstract Title: 

Blood-brain barrier permeability study of ginger constituents.

Abstract: 

Ginger, the rhizome of Zingiber officinale Roscoe is of great importance in the traditional medicine for the treatment of various diseases. More than 400 constituents have been reported in the plant, the most important ones being the gingerol and shogaol derivatives. Positive effects of ginger extracts and isolated [6]-gingerol have been proved in animal models of anxiety, Alzheimer's disease, Parkinson's disease and epilepsy. Taken in consideration these promising positive effects of ginger and its constituents in the central nervous system, the isolation of gingerol and shogaol derivatives ([6]-gingerol (1), [8]-gingerol (2), [10]-gingerol (3), [6]-shogaol (4), [10]-shogaol (5), 1-dehydro-[6]-gingerdione (6), 1-dehydro-[10]-gingerdione (7)) and investigation of their transcellular passive diffusion across the blood-brain barrier (BBB) were carried out. For this purpose, a Parallel Artificial Membrane Permeability Assay for the Blood-Brain Barrier (PAMPA-BBB) was chosen that had previously been validated for natural compounds. Based on our results, [6]-gingerol, [8]-gingerol and [6]-shogaol were found to be able to penetrate the BBB via passive diffusion, suggesting them to contribute to the positive effects of ginger extracts in the central nervous system.

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PMID: 

Anal Cell Pathol (Amst). 2019 ;2019:5134156. Epub 2019 Mar 6. PMID: 30963020

Abstract Title: 

Effect of Shogaol on the Expression of Intestinal Stem Cell Markers in Experimentally Induced Colitis in BALB/c Mice.

Abstract: 

Aim: This study is aimed at investigating the effect of Shogaol, a phenolic constituent of ginger, on dextran sodium sulfate- (DSS-) induced ulcerative colitis (UC) in mice in comparison with 6-thioguanine (6-TG), an immune-suppressant chemotherapeutic medicine used for treatment of ulcerative colitis.Material & Methods: Thirty-six adult, male and female BALB/c mice were randomly divided into six groups: group 1 (control negative) not exposed to DSS and did not receive any treatment, group 2 (control positive) exposed to DSS but did not receive any treatment, group 3 exposed to DSS and treated by 0.1 mg/kg of 6-thioguanine, and groups 4, 5, and 6 exposed to DSS and treated by 10, 20, and 40 mg/kg b.w. Shogaol, respectively. At day 56, the mice were checked for their disease activity index (DAI) and they were sacrificed. The colons of the mice were examined for length measurement, histological index score, and the expression of CD133 and CD34 stem cell markers.Results: Shogaol showed a better curative effect than did 6-TG in repairing the colonic mucosal damages in DSS-exposed mice as indicated by the levels of CD133 and CD34 expression in the colonic crypts and by the DAI score, colon length measurements,&histological index score which were significantly reduced in mice treated by Shogaol, particularly the 20 and 40 mg/kg BW doses.Conclusion: The results of this study indicated that oral treatment with the ginger-derived substance Shogaol could be better than the conventional immunosuppressive chemotherapeutic remedy 6-TG in treatment of DSS-induced UC.

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PMID: 

J Photochem Photobiol B. 2019 Aug ;197:111518. Epub 2019 May 31. PMID: 31202076

Abstract Title: 

6-shogaol, a active constiuents of ginger prevents UVB radiation mediated inflammation and oxidative stress through modulating NrF2 signaling in human epidermal keratinocytes (HaCaT cells).

Abstract: 

Disclosure of ultraviolet (UV) radiation is the key feature from environment to cause redness of the skin, inflammation, photoaging and skin cancer. 6-Shogaol, a spicy compound secluded from ginger, which shows anti-inflammatory effects. Present study was demonstrated the role of 6-Shogaol on UVB induced oxidative stress and photoaging signaling in human epidermal keratinocytes (HaCaT cells). In this study, UVB-irratiation (180 mJ/cm) significantly elevated the intracellular ROS levels, depletion of antioxidants resulted in apoptotic HaCaT cells. MAPKs signaling are concerned in oxidative stress; these signaling events are measured as differentiation. We found that 6-shogaol prevents over expression of MAPKs (ERK1, JNK1&p38), in disclosure of UVB in HaCaT cells. Moreover, 6-shogaol infringed Bax and Bcl-2 in which 20 μg 6-shogaol influenced apoptosis in HaCaT cells by investigating augmented appearance of Bax and condensed appearance of Bcl-2 in contrast to control HaCaT cells. These results suggest that 6-shogaol could be a successful healing agent provides fortification against UVB-induced provocative andoxidative skin reimbursement.

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PMID: 

Am J Physiol Renal Physiol. 2019 Jul 17. Epub 2019 Jul 17. PMID: 31313953

Abstract Title: 

6-Shogaol protects against ischemic acute kidney injury by modulating NFκB and heme oxygenase-1 pathways.

Abstract: 

Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy. Ginger is one of the most widely consumed spices in the world and 6-Shogaol, a major Ginger metabolite, has anti-inflammatory effects in neuronal and epithelial cells. Here, we demonstrate that 6-Shogaol treatment protected against renal IR injury with decreased plasma creatinine, blood urea nitrogen and kidney NGAL mRNA synthesis compared to vehicle-treated mice subjected to renal IR. In addition, 6-Shogaol treatment reduced kidney inflammation (decreased pro-inflammatory cytokine and chemokine synthesis as well as neutrophil infiltration) and apoptosis (decreased TUNEL positive renal tubular cells) when compared to vehicle-treated mice subjected to renal IR. In cultured human and mouse kidney proximal tubule cells, 6-Shogaol significantly attenuated TNF-α induced inflammatory cytokine and chemokine mRNA synthesis. Mechanistically, 6-Shogaol significantly attenuated TNF-α induced NFκB activation in human renal proximal tubule cells by reducing IKKαβ/IκBα phosphorylation. Furthermore, 6-Shogaol induced a cytoprotective chaperone heme oxygenase-1 (HO-1) via p38 MAPK activationand. Consistent with these findings, pretreatment with a HO-1 inhibitor Zinc Protoporphyrin IX completely prevented 6-Shogaol-mediated protection against ischemic AKI in mice. Taken together, our studies show that 6-Shogaol protects against ischemic AKI by attenuating NFκB activation and inducing HO-1 expression. 6-Shogaol may provide a potential therapy for ischemic AKI during the perioperative period.

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PMID: 

Saudi J Biol Sci. 2019 Feb ;26(2):382-389. Epub 2017 Aug 18. PMID: 31485182

Abstract Title: 

Biological activities of ginger against cadmium-induced renal toxicity.

Abstract: 

Our aim was to evaluate the protective and antioxidant effects of ginger extract against cadmium-induced renal toxicity in animal models and to support the use of ginger as anti-renal failure natural remedy. Seventy rats were examined in a 4-week experiment to evaluate the effect of Ginger () at doses of 100 and 200 mg/kg body weight on molecular DNA content, antioxidant status, and renal function in rats intoxicated with cadmium at dose of (5 mg/kg) using biochemical and histological analysis. Renal dysfunction, kidney tissue damage, and oxidative effect were evident in cadmium intoxicated rats as estimatedby significant increase in (creatinine, urea), decrease in (creatinine clearance and reabsorption rate of urine albumin), increase in MDA, decrease in total antioxidant status (TAC), reduction in DNA content, and histopathological changes of kidneys' tissues compared to control rats. Treatment withginger resulted in significant restoring of renal function biomarkers, TAC, molecular DNA, and histological improvements which occurs via free radical scavenging and regenerative mechanisms. The activity of ginger was supported by estimation of bioactive phenolic and falvinods constituents. Twenty-eight polyphenolic compounds were estimated in ginger extract; [6]-gingerol, [6]-shogaol, citral and pyrogallol were the highest amounts in ginger, and supposed to be responsible for its major antioxidant and free radical scavenging activity as shown by In vitro DPPH/β-carotene-linolic acid assay tests. Consequently, ginger extracts could have a potent protective effects against nephrotoxicity induced by various toxicants.

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PMID: 

Euro Surveill. 2013 Dec 5 ;18(49). Epub 2013 Dec 5. PMID: 24330942

Abstract Title: 

Case of vaccine-associated measles five weeks post-immunisation, British Columbia, Canada, October 2013.

Abstract: 

We describe a case of vaccine-associated measles in a two-year-old patient from British Columbia, Canada, in October 2013, who received her first dose of measles-containing vaccine 37 days prior to onset of prodromal symptoms. Identification of this delayed vaccine-associated case occurred in the context of an outbreak investigation of a measles cluster.

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PMID: 

Eur J Pharm Sci. 2019 Jul 1 ;135:91-102. Epub 2019 May 9. PMID: 31078644

Abstract Title: 

Curcumin ameliorates the targeted delivery of methotrexate intercalated montmorillonite clay to cancer cells.

Abstract: 

Montmorillonite Clay (MMT) is aimed to develop as an orally administrable drug delivery vehicle with enhanced efficacy. Aiming to enhance the therapeutic index of methotrexate, curcumin is concomitantly used with methotrexate in the present study. Being folate antagonist in nature, methotrexate is internalized into cells by folate receptor (FR); which is over-expressed in certain human cancer cells such as cervical carcinoma cells (HeLa). Firstly, montmorillonite Clay (MMT) is organically modified (OMMT) with cetyl trimethyl ammonium bromide (CTAB) and used to intercalate curcumin and methotrexate separately, designated as OMMT-Cur and OMMT-MTX, respectively. XRD pattern demonstrated successful intercalation of therapeutics and an increase in clay interlayer distance facilitated by CTAB. The dissolution kinetics of methotrexate follows Higuchi model for both Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), while the release kinetics for curcumin fitted into Higuchi model for SGF and Hixson-Crowell model for SIF, respectively. OMMT-MTX are able to discriminate FR-positive HeLa cells from FR-negative breast cancer cells (MCF7); irrespective of alike cellular phenotypes. Further, the pre-treatment of HeLa cells with curcumin improves its sensitivity towards methotrexate causing a greater killing of the Hela cells. Together, the results propose the concomitant use of curcumin and methotrexate for successfully targeting highly invasive FR-positive carcinomas by means of folate receptor using MMTs.

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PMID: 

Nanomedicine. 2013 Feb ;9(2):212-21. Epub 2012 Jun 9. PMID: 22687898

Abstract Title: 

Autophagy is involved in nanoalumina-induced cerebrovascular toxicity.

Abstract: 

UNLABELLED: The current study focused on blood-brain barrier disruption and neurovascular damage induced by engineered nanomaterials. Exposure to nanoalumina, but not to nanocarbon, induced a dose-dependent mitochondrial potential collapse, increased autophagy of brain endothelial cells, and decreased expression of the tight-junction proteins occludin and claudin-5. Inhibition of autophagy by pretreatment with Wortmannin attenuated the effects of nanoalumina on decreased claudin-5 expression; however, it did not affect the disruption of occludin. These findings were confirmed in mice by administration of nanoalumina into the cerebral circulation. Systemic treatment with nanoalumina elevated autophagy-related genes and autophagic activity in the brain, decreased tight-junction protein expression, and elevated blood-brain barrier permeability. Finally, exposure to nanoalumina, but not to nanocarbon, increased brain infarct volume in mice subjected to a focal ischemic stroke model. Overall, our study reveals that autophagy constitutes an important mechanism involved in nanoalumina-induced neurovascular toxicity in the central nervous system.FROM THE CLINICAL EDITOR: In this paper, the effects of nanoalumina on the permeability of the blood-brain barrier is reported, suggesting that autophagy is an important mechanism in nanoalumina-induced neurovascular toxicity.

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PMID: 

Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30:109757. Epub 2019 Aug 30. PMID: 31476335

Abstract Title: 

Ascorbic acid presents rapid behavioral and hippocampal synaptic plasticity effects.

Abstract: 

Growing evidence has suggested that ascorbic acid may exhibit rapid anxiolytic and antidepressant-like effects. In this study the effects of a single administration of ascorbic acid (1 mg/kg, p.o.), ketamine (1 mg/kg, i.p., a fast-acting antidepressant) and fluoxetine (10 mg/kg, p.o., conventional antidepressant) were investigated on: a) behavioral performance in the novelty suppressed feeding (NSF) test; b) hippocampal synaptic protein immunocontent; c) dendritic spine density and morphology in the dorsal and ventral dentate gyrus (DG) of the hippocampus and d) hippocampal dendritic arborization. Ascorbic acid or ketamine, but not fluoxetine, decreased the latency to feed in the NSF test in mice. This effect was accompanied by increased p70S6K (Thr) phosphorylation 1 h after ascorbic acid or ketamine treatment, although only ascorbic acid increased synapsin I immunocontent. Ketamine administration increased the dendritic spine density in the dorsal DG, but none of the treatments affected the maturation of dendritic spines in this region. In addition, both ascorbic acid and ketamine increased the dendritic spine density in the ventral DG, particularly the mature spines. Sholl analysis demonstrated no effect of any treatment on hippocampal dendritic arborization. Altogether, the results provide evidence that the behavioral and synaptic responses observedfollowing ascorbic acid administration might occur via the upregulation of synaptic proteins, dendritic spine density, and maturation in the ventral DG, similar to ketamine. These findings contribute to understand the cellular targets implicated in its antidepressant/anxiolytic behavioral responsesand support the notion that ascorbic acid may share with ketamine the ability to increase synaptic function.

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PMID: 

Braz J Med Biol Res. 2019 ;52(9):e8290. Epub 2019 Sep 2. PMID: 31482998

Abstract Title: 

Local treatment with ascorbic acid accelerates recovery of post-sutured Achilles tendon in male Wistar rats.

Abstract: 

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.

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