PMID: 

Int Immunopharmacol. 2019 Jul 17 ;75:105742. Epub 2019 Jul 17. PMID: 31325727

Abstract Title: 

Activation of Nrf2/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis.

Abstract: 

BACKGROUND: Osteoarthritis (OA), one of the prevailing joint degenerative disorders, contributes to the disability around the world. However, no effective therapeutic was introduced currently. Myricetin was reported to possess the function of anti-inflammatory, anti-diabetic and anti-cancer. Thus, we investigate the protection role of myricetin in OA progression and the potential molecular mechanism in present study.METHODS: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-13, Aggrecan, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT, Nrf2/HO-1 and nuclear factor kappa B (NF-κB) signaling pathways were analyzed by western blotting, and immunofluorescence was used to assess the expression of Nrf2, Collagen II and MMP13. The in vitro effect of myricetin was evaluated by intragastric administration intoa mouse osteoarthritis model induced by destabilization of the medial meniscus.RESULTS: Myricetin not only inhibited the generation of inflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α and IL-6, but also suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in human chondrocytes under IL-1β stimulation. Moreover, Metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), which resulted in the degradation of cartilage, were also suppressed in chondrocytes with the treatment of myricetin. To explore the potential mechanism, we found out that myricetin suppressed NF-κB signaling pathway through Nrf2/HO-1 axis in human chondrocytes. Besides, myricetin regulated the Nrf2 signaling pathway through PI3K/Akt pathway. In addition, in vivo study demonstrated that myricetin could ameliorated the progression of OA in mice DMM model through PI3K/Akt mediated Nrf2 signaling pathway.CONCLUSION: Taken together, our data first demonstrated that myricetin possesses the therapeutic potential on OA through PI3K/Akt mediated Nrf2/HO-1 signaling pathway.

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PMID: 

Ecotoxicol Environ Saf. 2019 Jul 17 ;182:109447. Epub 2019 Jul 17. PMID: 31325809

Abstract Title: 

Selenium decreases methylmercury and increases nutritional elements in rice growing in mercury-contaminated farmland.

Abstract: 

Methylmercury (MeHg) in rice grains grown in Hg-contaminated areas has raised environmental health concerns. Pot experiments found that selenium (Se) could reduce MeHg levels in rice grains. However, relatively high levels of Se (up to 6 mg/kg) were applied in these pot experiments, which may have adverse effects on the soil ecology due to the toxicity of Se. The aims of this work were thus to study 1) the effect of low levels of Se on the accumulation and distribution of Hg, especially MeHg, in rice plants grown in a real Hg-contaminated paddy field and 2) the effect of Se treatment on Se and other nutritional elements (e.g., Cu, Fe, Zn) in grains. A field study amended with different levels of Se was carried out in Hg-contaminated paddy soil in Qingzhen, Guizhou, China. The levels of MeHg and total Hg were studied using cold vapor atomic fluorescence spectrometry (CVAFS) and inductively coupled plasma mass spectrometry (ICP-MS). The distribution and relative quantification of elements in grains were examined by synchrotron radiation X-ray fluorescence analysis (SR-XRF). This field study showed that low levels of Se(0.5 μg/mL, corresponding to 0.15 mg Se/kg soils) could significantly reduce total Hg and MeHg in rice tissues. Se treatment also reduced Hg distribution in the embryo and endosperm and increased the levels of Fe, Cu, Zn and Se in grains and especially embryos. This field study implied that treatment with an appropriate level of Se is an effective approach to not only decrease the level of MeHg but to also increase the levels of nutritional elements such as Fe, Cu, Zn and Se in rice grains, which could bring beneficial effects for rice-dependent residents living in Hg-contaminated areas.

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PMID: 

Dose Response. 2019 Apr-Jun;17(2):1559325819855538. Epub 2019 Jun 11. PMID: 31217757

Abstract Title: 

Sulforaphane Attenuates Endometriosis in Rat Models Through Inhibiting PI3K/Akt Signaling Pathway.

Abstract: 

Sulforaphane exerts anti-inflammatory activity in inflammatory diseases. The endometriosis (EM) is accompanied by chronic inflammation. The present study aims to explore the therapeutic effects of sulforaphane on EM and its underlying mechanism. An EM rat model was established by transplantation of autologous fragments. The rats were intragastrically administered sulforaphane (5 mg/kg, 15 mg/kg, and 30 mg/kg) for 3 weeks. The volumes of endometriotic foci and adhesion score were calculated at the end of the experiment. Levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA). Expressions of VEGF, B-cell lymphoma/leukemia 2 (Bcl-2), Bax, cleaved caspase-3, PI3K, and Akt in endometrial tissue were determined by Western blotting. Relative expressions of PI3K and Akt were determined by quantitative polymerase chain reaction. Posttreatment of sulforaphane dose-dependently decreased the volumes of endometriotic foci and adhesion score in EM model. Additionally, posttreatment of sulforaphane inhibited levels of IL-6, IL-10, TNF-α, IFN-γ, and VEGF in peritoneal fluid and plasma. Posttreatment of sulforaphane regulated the expressions of VEGF, bcl-2, Bax, and cleaved Caspase-3 in EM model. The underlying mechanism revealed that sulforaphane attenuated EM in the rat model by inhibition of PI3K/Akt signaling pathway.

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PMID: 

J Agric Food Chem. 2019 Jul 17 ;67(28):7844-7854. Epub 2019 Jul 9. PMID: 31241937

Abstract Title: 

Sulforaphane Inhibits Nonmuscle Invasive Bladder Cancer Cells Proliferation through Suppression of HIF-1α-Mediated Glycolysis in Hypoxia.

Abstract: 

Bladder cancer is the fourth common cancer among men and more than 70% of the bladder cancer is nonmuscle invasive bladder cancer (NMIBC). Because of its high recurrence rate, NMIBC brings to patients physical agony and high therapy costs to the patients' family and society. It is imperative to seek a natural compound to inhibit bladder cancer cell growth and prevent bladder cancer recurrence. Cell proliferation is one of the main features of solid tumor development, and the rapid tumor cell growth usually leads to hypoxia due to the low oxygen environment. In this study we found that sulforaphane, a natural chemical which was abundant in cruciferous vegetables, could suppress bladder cancer cells proliferation in hypoxia significantly stronger than in normoxia (

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Google has recently (June 2019) used their power to manipulate public opinion in favor of the Pro Vaccine Argument!

PMID: 

Eur J Pharmacol. 2019 Jun 29 ;859:172513. Epub 2019 Jun 29. PMID: 31260654

Abstract Title: 

Combinations of the antioxidants sulforaphane or curcumin and the conventional antineoplastics cisplatin or doxorubicin as prospects for anticancer chemotherapy.

Abstract: 

Drugs used in clinical oncology have narrow therapeutic indices with adverse toxicity often involving oxidative damage. Chemoresistance to these conventional antineoplastics is usually mediated by oxidative stress-upregulated pathways such as those of nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1 alpha (HIF-1α). Accordingly, the use of antioxidants in combinational approaches has begun to be considered for fighting cancer because of both the protective role against adverse effects and the ability to sensitize chemoresistant cancer cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been identified as a mediator of the cytoprotection but it is not regularly associated with tumor chemosensitization. However, some Nrf2 inducers could be exerting cytoprotective and chemosensitizing roles through a simple integrated mechanism in which the cellular level of reactive oxygen species is controlled, thus inhibiting the oxidative damage in non-target tissues and the tumor chemoresistance mediated by NF-κB or HIF-1α. As examples to show the general idea of this antioxidant combination chemotherapy, this review explores the preclinical information available for four combinations, each composed by a paradigmatic oncological drug (cisplatin or doxorubicin) and a recognized antioxidant (sulforaphane or curcumin). The issues for translating these outcomes to clinical trials are briefly discussed.

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PMID: 

Am J Clin Nutr. 2019 Jul 3. Epub 2019 Jul 3. PMID: 31268126

Abstract Title: 

Dose-dependent detoxication of the airborne pollutant benzene in a randomized trial of broccoli sprout beverage in Qidong, China.

Abstract: 

BACKGROUND: Airborne pollutants have collectively been classified as a known human carcinogen and, more broadly, affect the health of hundreds of millions of people worldwide. Benzene is a frequent component of air pollution, and strategies to protect individuals against unavoidable exposure to this and other airborne carcinogens could improve the public's health. Earlier clinical trials in Qidong, China, demonstrated efficacy in enhancing the detoxication of benzene using a broccoli sprout beverage.OBJECTIVES: A randomized, placebo-controlled, multidose trial of a broccoli sprout beverage was designed to determine the lowest effective concentration that enhances benzene detoxication adjudged by enhanced excretion of the urinary biomarker, S-phenylmercapturic acid (SPMA).METHODS: Following informed consent, 170 subjects were randomly assigned in 5 blocks of 34 each to drink either a placebo beverage (n = 55) or 1 of 3 graded concentrations of a broccoli sprout beverage [full (n = 25), one-half (n = 35), and one-fifth (n = 55)] for 10 consecutive days. Concentrations of SPMA arising through induced benzene conjugation with glutathione were quantified by MS in sequential 12-h overnight urine collections during the intervention.RESULTS: MS was also used to quantify urinary sulforaphane metabolites in each dosing regimen that resulted in a median 24-h urinary output of 24.6, 10.3, and 4.3µmol, respectively, confirming a dose-dependent de-escalation of the inducing principle within the beverage. A statistically significant increase in benzene mercapturic acids in urine was found for the high-dose group (+63.2%) during the 10-d period. The one-half dose (+11.3%) and one-fifth dose groups (-6.4%) were not significantly different from placebo controls.CONCLUSIONS: An intervention with a broccoli sprout beverage enhanced the detoxication of benzene, an important airborne pollutant, when dosed at a concentration evoking a urinary elimination of∼25 µmol sulforaphane metabolites per day, and it portends a practical and frugal population-based strategy to attenuate associated long-term health risks of air pollution. This trial was registered at clinicaltrials.gov as NCT02656420.

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PMID: 

Biochem J. 2002 Jul 15 ;365(Pt 2):489-96. PMID: 11939906

Abstract Title: 

Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2.

Abstract: 

Prostaglandin (PG) E(1) has been shown to possess anti-inflammatory properties and to modulate vascular reactivity. These activities are sometimes distinct from those of PGE(2), suggesting that endogenously produced PGE(1) may have some beneficial therapeutic effects compared with PGE(2). Increasing the endogenous formation of PGE(1) requires optimization of two separate processes, namely, enrichment of cellular lipids with dihomo-gamma-linolenic acid (20:3 n-6; DGLA) and effective cyclo-oxygenase-dependent oxygenation of substrate DGLA relative to arachidonic acid (AA; 20:4 n-6). DGLA and AA had similar affinities (K(m) values) and maximal reaction rates (V(max)) for cyclo-oxygenase-2 (COX-2), whereas AA was metabolized preferentially by cyclo-oxygenase-1 (COX-1). To overcome the kinetic preference of COX-1 for AA, CP-24879, a mixed Delta(5)/Delta(6) desaturase inhibitor, was used to enhance preferential accumulation of DGLA over AA in cells cultured in the presence of precursor gamma-linolenic acid (18:3 n-6). This protocol was tested in two cell lines and both yielded a DGLA/AA ratio of approx. 2.8 in the total cellular lipids. From the enzyme kinetic data, it was calculated that this ratio should offset the preference of COX-1 for AA over DGLA. PGE(1) synthesis in the DGLA-enriched cells was increased concurrent with a decline in PGE(2) formation. Nevertheless, PGE(1) synthesis was still substantially lower than that of PGE(2). It appears that employing a dietary or a combined dietary/pharmacological paradigm to augment the cellular ratio of DGLA/AA is not an effective route to enhance endogenous synthesis of PGE(1) over PGE(2), at least in cells/tissues where COX-1 predominates over COX-2.

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PMID: 

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2019 Jun 28 ;44(6):701-705. PMID: 31304933

Abstract Title: 

[Role of sulforaphane in improving negative symptoms and cognitive symptoms of schizophrenia and the underlying mechanism].

Abstract: 

The negative symptoms and cognitive symptoms of schizophrenia patients are still clinical problems to be solved. Schizophrenia patients are abnormal in oxidative stress, immune regulation, and anti-histone deacetylase (HDAC), while sulforaphane plays a role in anti-oxidative stress, anti-inflammation, and anti-HDAC. Therefore, the sulforaphane could improve the negative symptoms and cognitive deficits of schizophrenia.

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PMID: 

Biochim Biophys Acta Mol Basis Dis. 2019 Jul 8 ;1865(10):2586-2594. Epub 2019 Jul 8. PMID: 31295528

Abstract Title: 

Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1.

Abstract: 

Ethanol-induced apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is implicated in the Fetal Alcohol Spectrum Disorders (FASD). Studies have demonstrated that sulforaphane (SFN) can prevent ethanol-induced apoptosis in NCCs. The objective of this study is to investigate whether ethanol exposure can induce apoptosis in NCCs by inhibiting epithelial-mesenchymal transition (EMT) and whether SFN can prevent ethanol-induced apoptosis by epigenetically modulating the expression of Snail1, a key transcriptional factor that promotes EMT. We found that ethanol exposure resulted in a significant increase in apoptosis in NCCs. Co-treatment with SFN significantly reduced ethanol-induced apoptosis. Treatment with SFN also dramatically diminished ethanol-induced changes in the expression of E-cadherin and vimentin, and restored EMT in ethanol-exposed NCCs. In addition, ethanol exposure reduced the levels of trimethylation of histone H3 lysine 4 (H3K4me3) at the promoters of Snail1. SFN treatment diminished the ethanol-induced reduction of H3K4me3 at the promoter regions of the Snail1 gene, restored the expression of Snail1 and down-regulated Snail1 target gene E-cadherin. Knockdown of Snail1 significantly reduced the protective effects of SFN on ethanol-induced apoptosis. These results demonstrate that SFN can protect against ethanol-induced apoptosis by preventing ethanol-induced reduction in the levels of H3K4me3 at the promoters of Snail1, restoring the expression of Snail1 and EMT in ethanol-exposed NCCs.

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