PMID: 

Biol Trace Elem Res. 2019 Oct 25. Epub 2019 Oct 25. PMID: 31654258

Abstract Title: 

Curcumin and Selenium Prevent Lipopolysaccharide/Diclofenac-Induced Liver Injury by Suppressing Inflammation and Oxidative Stress.

Abstract: 

Diclofenac (DCL), an anti-inflammatory drug used to reduce pain and inflammation, ranks in the top causes of drug-induced liver injury. The inflammatory stress induced by inflammagens is implicated in DCL-induced liver injury. Curcumin (CUR) and selenium (Se) possess anti-inflammatory effects; therefore, this study evaluated their protective potential against lipopolysaccharide (LPS)/DCL-induced liver injury. Rats received CUR and/or Se for 7 days followed by a single intravenous administration of LPS 2 h before a single injection of DCL and two other doses of CUR and/or Se 2 and 8 h after DCL. Administration of nontoxic doses of LPS and DCL resulted in liver damage evidenced by the significantly elevated liver function markers in serum. LPS/DCL-induced liver injury was confirmed by histological alterations, increased lipid peroxidation and nitric oxide, and diminished glutathione and superoxide dismutase. CUR and/or Se prevented liver injury, histological alterations, and oxidative stress and boosted antioxidant defenses in LPS/DCL-induced rats. In addition, CUR and/or Se reduced serum C-reactive protein, liver pro-inflammatory cytokines, and the expression of TLR4, NF-κB, JNK, and p38, and upregulated heme oxygenase-1 (HO-1). In conclusion, CUR and/or Se mitigated LPS/DCL-induced liver injury in rats by suppressing TLR4 signaling, inflammation, and oxidative stress and boosting HO-1 and other antioxidants. Therefore, CUR and Se can hinder the progression and severity of liver injury during acute inflammatory episodes.

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PMID: 

Clin Nutr ESPEN. 2019 Dec ;34:1-7. Epub 2019 Oct 3. PMID: 31677697

Abstract Title: 

Selenium supplementation in HIV-infected individuals: A systematic review of randomized controlled trials.

Abstract: 

BACKGROUND & AIM: HIV infection has been linked to selenium deficiency which, in turn, is thought to be associated with a high risk of tuberculosis and mortality in HIV-infected patients. Furthermore, several trials have reported the beneficial effects of selenium supplementation in patients with HIV. However, the evidence remains inconclusive. Our study aimed to investigate whether daily selenium supplementation in patients infected with HIV delays the progression of HIV infection.METHODS: A systematic review was performed using EMBASE and Medline databases from January 2000 to June 2018. We included randomized clinical trials in adults comparing selenium with placebo and reporting outcomes including its effect on HIV viral load and cluster of differentiation 4 cell count (CD4).RESULTS: Six out of the 507 retrieved articles that met the inclusion criteria were used in this review. Reviewed studies show that daily supplementation with 200 μg selenium may improve the rate of cluster of differentiation 4 (CD4) count. The length of selenium supplementation and follow-up varied from 9 to 24 months. Supplements were well tolerated in all reviewed studies. Whether daily selenium supplementation in HIV-infected persons suppresses HIV-infection requires further investigation as existing data are heterogeneous.CONCLUSIONS: We found some clinical evidence that selenium supplementation can delay CD4 decline in HIV-infected patients, thus prolonging the onset of AIDS. However, we did not find quantifiable evidence that selenium supplementation suppresses or reduces HIV viral load.

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PMID: 

Neurotoxicology. 2019 Oct 31 ;76:99-110. Epub 2019 Oct 31. PMID: 31678059

Abstract Title: 

Neuroprotective mechanisms of selenium against arsenic-induced behavioral impairments in rats.

Abstract: 

Environmental pollution due to arsenic is associated with several adverse health effects including neurotoxicity in animals and humans. Selenium is a nutritionally essential trace metalloid well documented to elicit compelling pharmacological activities in vitro and in vivo. Report on the influence of selenium on arsenic-mediated behavioral derangement is lacking in literature. Hence, to fill this knowledge gap, rats were either exposed to arsenic per se in drinking water at 60 μg AsONa/L or co-administered with inorganic selenium at 0.25 mg/kg or organic selenium diphenyl diselenide (DPDS) at 2.5 mg/kg body weight for 45 successive days. Neurobehavioural data from rats in a new environment using video-tracking software evinced that inorganic and organic forms of selenium significantly (p 

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PMID: 

Public Health Nutr. 2019 Nov 5:1-8. Epub 2019 Nov 5. PMID: 31685060

Abstract Title: 

Lower circulating zinc and selenium levels are associated with an increased risk of asthma: evidence from a meta-analysis.

Abstract: 

OBJECTIVE: Previous studies evaluating the associations of circulating Zn and Se levels with asthma have produced inconsistent results. Therefore, we conducted a meta-analysis to summarize and quantitatively synthesize the evidence from observational research.DESIGN: Meta-analysis.SETTING: We searched PubMed, Web of Science and Scopus databases up to May 2019 for relevant available articles. Random-effects model was adopted to estimate the pooled standardized mean difference (SMD) with 95 % CI. Meta-regression analysis and 'leave-one-out' sensitivity analysis were used to assess heterogeneity.PARTICIPANTS: The meta-analysis focused on general populations.RESULTS: A total of twenty-six studies for Zn and forty studies for Se were included in the meta-analysis. The overall analyses identified that asthma patients had lower Zn (SMD = -0·40; 95 % CI -0·77, -0·03; I2 = 94·1 %) and Se (SMD = -0·32; 95 % CI -0·48, -0·17; I2 = 90·9 %) levels in serum or plasma compared with healthy controls. After removing the studies that contributed to the heterogeneity, the pooled SMD were -0·26 (95 % CI -0·40, -0·13; I2 = 37·42 %) for Zn and -0·06 (95 % CI -0·13, 0·02; I2 = 43·54 %) for Se.CONCLUSIONS: Lower circulating Zn and Se levels might be associated with an increased risk of asthma.

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PMID: 

J Clin Med. 2019 Oct 25 ;8(11). Epub 2019 Oct 25. PMID: 31717708

Abstract Title: 

Potential Therapeutic Targets of Quercetin and Its Derivatives: Its Role in the Therapy of Cognitive Impairment.

Abstract: 

Quercetin (QC) is a flavonoid and crucial bioactive compound found in a variety of vegetables and fruits. In preclinical studies, QC has demonstrated broad activity against several diseases and disorders. According to recent investigations, QC is a potential therapeutic candidate for the treatment of nervous system illnesses because of its protective role against oxidative damage and neuroinflammation. QC acts on several molecular signals, including ion channels, neuroreceptors, and inflammatory receptor signaling, and it also regulates neurotrophic and anti-oxidative signaling molecules. While the study of QC in neurological disorders has focused on numerous target molecules, the role of QC on certain molecular targets such as G-protein coupled and nuclear receptors remains to be investigated. Our analysis presents several molecular targets of QC and its derivatives that demonstrate the pharmacological potential against cognitive impairment. Consequently, this article may guide future studies using QC and its analogs on specific signaling molecules. Finding new molecular targets of QC and its analogs may ultimately assist in the treatment of cognitive impairment.

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PMID: 

Curr Drug Targets. 2019 Nov 12. Epub 2019 Nov 12. PMID: 31721700

Abstract Title: 

The therapeutic potential of quercetin in Parkinson's disease: Insights into its molecular and cellular regulation.

Abstract: 

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). PD is a multifactorial disorder, with several different factors being suggested to play a synergistic pathophysiological role, these including oxidative stress, autophagy, underlying pro-inflammatory events and neurotransmitters abnormalities. Overall, PD can be viewed as the product of a complex interaction of environmental factors acting on a given genetic background. The importance of this subject has attracted more attention to discover novel therapies to prevent as well as treat PD. According to previous research, drugs used to treatment of PD have indicated significant limitations. Therefore, the role of flavonoids has been extensively studied in PD treatment. Quercetin, a plant flavonol from the flavonoid group, has been considered as a supplemental therapy for PD. Quercetin has pharmacological functions in PD through controlling different molecular pathway. Although few studies intended to evaluate the basis for the use of quercetin in the context of PD have been conducted so far, at present there is very little evidence available addressing the underlying mechanisms of action.Various principal aspects of these treatment procedures remain unwell-known. Here we review currently existing knowledge supporting the use of quercetin for the clinical management of PD.

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PMID: 

Molecules. 2019 May 3 ;24(9). Epub 2019 May 3. PMID: 31058881

Abstract Title: 

The Anti-Staphylococcal Potential of Ethanolic Polish Propolis Extracts.

Abstract: 

The principal objective of this study was to determine the anti-staphylococcal potential of ethanol extracts of propolis (EEPs). A total of 20 samples of propolis collected from apiaries located in different regions of Poland were used in the study. The two-fold broth microdilution method revealed some important differences in the antimicrobial activity of investigated EEPs. Up to the concentration of 4096µg/mL no activity was observed against Gram-negative bacteria (and). Staphylococci exhibited much higher susceptibility. The highest efficiency observed for EEP12 and EEP20 (MIC values ranged between 32 and 256µg/mL). However, the achievement of bactericidal effect usually required higher concentrations. In the case of clinical isolates ofMBC values for EEP12 and EEP20 ranged from 512 to 1024µg/mL. The HPLC analysis revealed that these two products contained a higher concentration of flavonoids (flavonols, flavones, and flavanones) compared to other investigated EEPs. In checkerboard test, a synergistic anti-staphylococcal effect was observed for the action of EEP20 in combination withamikacin, kanamycin, gentamycin, tetracycline, and fusidic acid (all these antibiotics inhibit protein synthesis). Moreover, the investigated EEPs effectively eradicated staphylococcal biofilm. The obtained results clearly confirm the high anti-staphylococcal potential of propolis harvested in Polish apiaries.

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PMID: 

J Cell Physiol. 2019 Aug ;234(10):17392-17404. Epub 2019 Feb 20. PMID: 30790292

Abstract Title: 

Oroxylin A increases the sensitivity of temozolomide on glioma cells by hypoxia-inducible factor 1α/hedgehog pathway under hypoxia.

Abstract: 

Microenvironmental hypoxia-mediated drug resistance is responsible for the failure of cancer therapy. To date, the role of the hedgehog pathway in resistance to temozolomide (TMZ) under hypoxia has not been investigated. In this study, we discovered that the increasing hypoxia-inducible factor 1α (HIF-1α) activated the hedgehog pathway in hypoxic microenvironment by promoting autocrine secretion of sonic hedgehog protein (Shh), and then upregulating transfer of Gli1 to the nucleus, finally contributed to TMZ resistance in glioma cells. Oroxylin A (C16H12O5), a bioactive flavonoid, couldinduce HIF-1α degradation via prolyl-hydroxylases-VHL signaling pathway, resulting in the inactivation of the hedgehog. Besides, oroxylin A increased the expression of Sufu, which is a negative regulator of Gli1. By this mechanism, oroxylin A sensitized TMZ on glioma cells. U251 intracranial transplantation model and GL261 xenograft model were used to confirm the reversal effects of oroxylin A in vivo. In conclusion, our results demonstrated that HIF-1α/hedgehog pathway conferred TMZ resistance under hypoxia, and oroxylin A was capable of increasing the sensitivity of TMZ on glioma cells invitro and in vivo by inhibiting HIF-1α/hedgehog pathway and depressing the activation of Gli1 directly.

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PMID: 

Cancers (Basel). 2019 Mar 12 ;11(3). Epub 2019 Mar 12. PMID: 30871117

Abstract Title: 

Long-Term Exposure to Oroxylin A Inhibits Metastasis by Suppressing CCL2 in Oral Squamous Cell Carcinoma Cells.

Abstract: 

Oroxylin A (Oro-A), the main bioactive flavonoid extracted from, has been reported to inhibit migration in various human cancer cell models. In this study, we further explored the anti-migration effects of Oro-A on oral squamous cell carcinoma (OSCC) cells and investigated the underlying mechanisms. A 24-h (short-term) exposure of OSCC cells to non-cytotoxic concentrations (5⁻20 μM) of Oro-A significantly suppressed cell migration according to a wound-healing assay. Furthermore, a 30-day exposure (long-term) to Oro-A (20 μM), which did not exhibit a cytotoxic effect on OSCC cells, significantly suppressed cell migration more than short-term Oro-A exposure. To uncover the molecular mechanisms underlying the inhibitory effect of long-term Oro-A exposure on OSCC migration, a cDNA microarray and the Ingenuity software were used. Overall, 112 upregulated and 356 downregulated genes were identified in long-term Oro-A-exposed cells compared with untreated OSCC cells.Among them, 75 genes were reported to be associated with cancer cell migration. Consistent with the cDNA microarray results, we found that the expression levels of several cell migration-related genes, such as LCN2, ID-1, MDK, S100A9 and CCL2, were significantly decreased in long-term Oro-A-exposedOSCC cells using a quantitative real-time polymerase chain reaction (Q-PCR) assay. The Western blotting and enzyme-linked immunosorbent assay (ELISA) results also demonstrated that CCL2 expression at the mRNA and protein levels was significantly decreased in long-term Oro-A-exposed OSCC cells compared with untreated OSCC cells. Moreover, the expression levels of downstream CCL2 targets, including p-ERK1/2, NFκB, MMP2, and MMP9, were also decreased in long-term Oro-A-exposed OSCC cells. Further, Oro-A treatment suppressed in vivo metastasis. These results suggest that long-term Oro-A treatment inhibits metastasis via CCL2 signaling in OSCC cells.

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PMID: 

Biomed Res Int. 2019 ;2019:9241769. Epub 2019 Jun 23. PMID: 31341911

Abstract Title: 

Oroxylin A Suppresses the Cell Proliferation, Migration, and EMT via NF-B Signaling Pathway in Human Breast Cancer Cells.

Abstract: 

Oroxylin A is a natural extract and has been reported to have a remarkable anticancer function. However, the mechanism of its anticancer activity remains not quite clear. In this study, we examined the inhibiting effects of Oroxylin A on breast cancer cell proliferation, migration, and epithelial-mesenchymal transition (EMT) and its possible molecular mechanism. The cytoactive and inflammatory factors were analyzed via Cell Counting Kit-8 assay and ELISA assay, respectively. Flow cytometry and western blotting were used to assess the cell proliferation. In addition, a wound healing assay and transwell assay were used to detect cell invasion and migration. qRT-PCR and western blot were employed to determine the effect of Oroxylin A on the EMT formation. Moreover, expression level of protein related to NF-B signaling pathway was determined by western blot. The results revealed that Oroxylin A attenuated the cytoactivity of MDA-MB-231 cells in a dose- and a time-dependent manner. Moreover, cell proliferation, invasion, and migration of breast cancer cells were inhibited by Oroxylin A compared to the control. The mRNA and protein expression levels of E-cadherin were remarkably increased while N-cadherin and Vimentin remarkably decreased. Besides, Oroxylin A suppressed the expression of inflammatory factors and NF-B activation. Furthermore, we also found that supplement of TNF-reversed the effects of Oroxylin A on the cell proliferation, invasion, migration, and EMT in breast cancer cells. Taken together, our results suggested that Oroxylin A inhibited the cell proliferation, invasion, migration, and EMT through inactivating NF-B signaling pathway in human breast cancer cells. These findings strongly suggest that Oroxylin A could be a therapeutic potential candidate for the treatment of breast cancer.

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