PMID: 

Mol Med Rep. 2019 Aug ;20(2):1761-1771. Epub 2019 Jun 20. PMID: 31257541

Abstract Title: 

Sulforaphane has a therapeutic effect in an atopic dermatitis murine model and activates the Nrf2/HO‑1 axis.

Abstract: 

Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by intense itching and recurrent eczematous lesions. Sulforaphane is known to attenuate oxidative stress, and tissue or cell damage in cerebral ischemia, brain inflammation and intracerebral hemorrhage. In the present study, a 2,4‑dinitrochlorobenzene (DNCB)‑induced AD mouse model was developed, and ear thickness, dermatitis score, eosinophil count, mast cell infiltration, and serum IgE levels were measured in DNCB‑induced AD and sulforaphane‑treated groups to demonstrate the therapeutic effects of sulforaphane. AD symptoms of DNCB‑induced mice were attenuated by sulforaphane treatment compared with those of negative control mice; furthermore, eosinophil count, mast cell infiltration and serum IgE levels were also reduced by sulforaphane treatment in DNCB‑induced AD mice. Western blot assays revealed that the expression levels of nuclear factor‑E2‑related factor 2 (Nrf2) and heme oxygenase-1 (HO‑1), which exhibit oxidation resistance, were increased by sulforaphane treatment in DNCB‑induced AD mice. The present study suggested that sulforaphane exerted a therapeutic effect in the AD mouse model through the activation of the Nrf2/HO‑1 axis as well as the suppression of Janus kinase 1/STAT3 signaling pathway.

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PMID: 

Medicines (Basel). 2019 Jun 27 ;6(3). Epub 2019 Jun 27. PMID: 31252639

Abstract Title: 

Effect of Sulforaphane and 5-Aza-2'-Deoxycytidine on Melanoma Cell Growth.

Abstract: 

UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2'-deoxycytidine (DAC) could slow melanoma cell growth. SFN is a natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase inhibitor.Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC.We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator cytokine-C-C motif ligand 5 (CCL-5)-was validated.These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth.

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PMID: 

J Cell Biochem. 2019 Jun 24. Epub 2019 Jun 24. PMID: 31232487

Abstract Title: 

Sulforaphane administration alleviates diffuse axonal injury (DAI) via regulation signaling pathway of NRF2 and HO-1.

Abstract: 

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) can alleviate diffuse axonal injury (DAI)-induced apoptosis by regulating expression of heme oxygenase-1 (HO-1), while sulforaphane (SFN) was shown to reduce oxidative stress by increasing the expression of Nrf2. Therefore, we aimed to investigate therapeutic effect of SFN in the treatment of DAI and the ability of SFN to reduce oxidative stress.METHODS: The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to observe the effects of HOand SFN on cell viability. Fluorometric assay, Western blot analysis, and flow cytometry were conducted to validate the protective role of SFN in an animal model of DAI. In addition, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in DAI rats treated by SFN, while Western blot, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were carried out to verify the effect of SFN in different animal groups.RESULTS: Cell viability was reduced by HOin a dose-dependent manner, while the treatment by SFN significantly promoted cell growth. Meanwhile the administration of SFN effectively reduced the levels of caspase-3/poly(ADP-ribose) polymerase (PARP) activity increased by the HOtreatment, indicating that the protective effect of SFN could be mediated by its ability to suppress caspase-3 activation and PARP cleavage. In addition, the SFN treatment reduced the intracellular reactive oxygen species (ROS) generation induced by HO. Moreover, the MDA levels of SOD/GPx activity in various rat groups showed the protective effects of SFN in DAI rats. It is suspected that the protective effect of SFN was exerted via the activation of the Nrf2/HO-1 signaling pathway. In this study, DAI and DAI + phosphate-buffered saline (PBS) groups also showed the presence of more TUNEL-positive cells compared with the sham-operated group, while the SFN treatment reduced the extent of neuronal apoptosis.CONCLUSIONS: By activating the Nrf2/HO-1 signaling pathway and reducing the activity of caspase-3, SFN reduces the apoptosis of neurons in brain trauma-induced DAI.

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PMID: 

Eur J Pharmacol. 2019 Jul 15 ;855:276-284. Epub 2019 May 14. PMID: 31100413

Abstract Title: 

Sulforaphane treatment reverses corticosteroid resistance in a mixed granulocytic mouse model of asthma by upregulation of antioxidants and attenuation of Th17 immune responses in the airways.

Abstract: 

Sulforaphane has received considerable attention in recent years due to its antioxidant and anti-inflammatory properties. Its preventive effect in the inhibition of airway inflammation is known; however, whether it affects mixed granulocyte asthma (corticosteroid resistance phenotype) is largely undiscovered. Therefore, we assessed the effect of pharmacological activation of Nrf2, a redox-sensitive transcription factor, using sulforaphane in a mouse model of mixed granulocyte airway inflammation. Mice were sensitized and challenged with cockroach allergen extract (CE), and airway inflammatory parameters and markers of steroid resistance [Nrf2 activity, oxidant-antioxidant balance in airway epithelial cells (AECs)/lung, and IL-17A-related pathway in Th17 cells and dendritic cells (DCs)] were investigated. Our results show that sulforaphane administration reduced neutrophilic airway inflammation, myeloperoxidase (MPO) activity, and Th17 immune responses in a mixed granulocyte mouse model of asthma through Nrf2 activation. On the other hand, corticosteroid treatment decreased Th2/eosinophilic immune responses but had little on Th17/neutrophilic immune responses. However, combined treatment with both almost completely blocked both neutrophilic/eosinophilic and Th17/Th2 immune responses in the lung. Sulforaphane treatment led to induction of antioxidant enzymes (SOD, GPx) in AECs and pulmonary non-enzymatic antioxidants. Further, it led to reduction in inflammatory cytokines (IL-6/IL-23/IL-17A) in Th17 cells/CD11c + DCs during mixed granulocytic inflammation. Collectively, our study presents the evidence that activation of Nrf2 by sulforaphane reduces neutrophilic airway inflammation by upregulation of antioxidants and downregulation of inflammatory cytokines in airways. This is possibly the basis for reversal of corticosteroid resistance in this model. This shows the therapeutic potential of sulforaphane in mixed granulocyte asthma.

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PMID: 

Theriogenology. 2019 Sep 27 ;142:138-148. Epub 2019 Sep 27. PMID: 31593881

Abstract Title: 

Maternal exposure to bisphenol A during pregnancy interferes ovaries development of F1 female mice.

Abstract: 

This study was conducted to investigate the effects of maternal exposure bisphenol A (BPA) on ovaries development of F1 female mice. The BPA exposure model of pregnant mice was prepared by intragastric administration of BPA at the doses of 0, 2.5, 5, 10, 20, 40 mg kg dat gestation day (GD) 0.5-17.5. The ovarian index of the offspring mice was calculated at postnatal day (PND) 21 and PND 56. The results showed that BPA at 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg significantly increased the abortion rate of the pregnant mice, and each dose of BPA significantly reduced the survival rate of the pups (P 

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PMID: 

Exp Ther Med. 2019 Sep ;18(3):1745-1751. Epub 2019 Jul 5. PMID: 31410133

Abstract Title: 

Anti-inflammatory and anti-apoptosis activity of taraxasterol in ulcerative colitisand.

Abstract: 

Ulcerative colitis is closely associated with colorectal cancer, the long-standing chronic inflammation being the key etiology of ulcerative colitis. The aim of the present study was to identify the anti-inflammatory and anti-apoptosis activity of taraxasterol in ulcerative colitis. MTT assay was used to obtain the optimal concentrations of lipopolysaccharide (LPS) and taraxasterol for cell treatments. A mouse model of colitis was established via dextran sodium sulphate (DSS) administration. Levels of IL-6 and TNF-α were detected through ELISA. Flow cytometry and western blotting were used to detect apoptosis and related protein expression levels, respectively. Hematoxylin and eosin staining was performed to detect the pathological damage. The results from the MTT assay identified the optimal concentration of LPS and taraxasterol, and ELISA results demonstrated that taraxasterol treatment decreased the expression levels of IL-6 and TNF-αand, in a dose-dependent manner. Taraxasterol treatment inhibited apoptosis, and reduced the protein levels of p53, Bcl-2 associated X (BAX) and caspase-3. Finally, pathological damages were reduced in colonic tissues of mice treated with taraxasterol. Taken together, taraxasterol treatment markedly inhibited inflammation and apoptosis in ulcerative colitis. Therefore, taraxasterol may be a promising agent for decreasing the inflammatory response in ulcerative colitis and other inflammation-related diseases.

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PMID: 

IUBMB Life. 2019 Oct 6. Epub 2019 Oct 6. PMID: 31587481

Abstract Title: 

Bisphenol A aggravates renal ischemia-reperfusion injury by disrupting mitochondrial homeostasis and N-acetylcysteine mitigates the injurious outcomes.

Abstract: 

Exposure to bisphenol A (BPA), a chemical generally used in consumer products, becomes a global public health concern, as humans are increasingly exposed through their daily consuming activities. Renal ischemia-reperfusion (RIR) is the major cause of acute kidney injury with high prevalence and increased long-term risks for multiple comorbidities and mortality. As the kidney is susceptible to these conditions, we explored whether the outcomes following the RIR episode could be influenced by BPA exposure, and investigated the therapeutic possibility by N-acetylcysteine (NAC) including the mechanisms involved. Three groups of male Wistar rats were fed with vehicle, BPA 5, and 50 mg/kg, respectively, for five consecutive weeks then underwent the sham operation. Three other groups with identical treatment underwent bilateral renal IR induction (45-min ischemia followed by 24-hr reperfusion). An additional RIR group was treated with BPA 50 plus NAC 100 mg/kg. BPA-exposedrats that encountered RIR episode showed dose-dependent worsening of RIR injury as evidenced by augmentations of renal dysfunction and histopathological abnormalities, oxidative stress, apoptosis, mitochondrial functional impairment, mitochondrial dynamic, and mitophagy disproportion compared with the vehicle-exposed RIR group. The NAC therapy considerably attenuated the exacerbated effects of BPA, which was associated with increased AMP-activated protein kinase (AMPK), PGC-1α, silent information regulator 3 or sirtuin 3 (SIRT3), and mitofusin 2 (MFN2) expressions but decreased Phosphorylateddynamin-related protein 1 (p-DRP1)/Dynamin-related protein 1 (DRP1), PTEN-induced putative kinase (PINK), and PARKIN expressions. These findings reveal the detrimental effect of repeated BPA exposure on the renal outcomes following the IR episode, and further demonstrate the protective efficacy ofNAC by maintaining mitochondrial homeostasis, which is, partly, mediated through the AMPK-PGC-1α-SIRT3 axis.

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PMID: 

Toxicology. 2019 Sep 28:152299. Epub 2019 Sep 28. PMID: 31574244

Abstract Title: 

Bisphenol A triggers axonal injury and myelin degeneration with concomitant neurobehavioral toxicity in C57BL/6J male mice.

Abstract: 

Bisphenol A (BPA) is a ubiquitously distributed endocrine disrupting chemical (EDC). Its exposure in humans has been of concern due to its increased application in the products of day to day use. BPA has been reported to cause toxicity in almost all the vital organ systems even at a very low dose level. It crosses the blood brain barrier and causes neurotoxicity. We studied the effect of BPA on the cerebral cortex of C57BL/6 J mice and examined whether BPA exposure alters the expression of axonal and myelin structural proteins. Male mice were dosed orally to 40 μg and 400 μg BPA/kg body weight for 60 days. BPA exposure resulted in memory loss, muscle coordination deficits and allodynia. BPA exposure also causeddegeneration of immature and mature oligodendrocytes as evaluated by decreased mRNA levels of 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase), nestin, myelin basic protein (MBP) and myelin-associated glycoprotein-1 (MAG-1) genes revealing myelin related pathology. It was observed that subchronic BPA exposure caused neuroinflammation through deregulation of inflammatory cytokines mRNA and protein expression which further resulted into neurotoxicity through axonal as well as myelin degeneration in the brain. BPA also caused increased oxidative stress in the brain. Our study indicates thatlong term subchronic low dose exposure to BPA has potential to cause axonal degeneration and demyelination in the oligodendrocytes and neurons which may have implications in neurological and neuropsychological disorders including multiple sclerosis (MS), neuromyelitis optica and others.

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PMID: 

Curr Eye Res. 2019 Oct 4:1-9. Epub 2019 Oct 4. PMID: 31557061

Abstract Title: 

A Mechanism Study of Electroacupuncture for Dry Eye Syndrome by Targeting Conjunctival Cytokine Expressions.

Abstract: 

: To discuss the immunological mechanism in electroacupuncture (EA) treatment of dry eye syndrome (DES) by targeting the changes in conjunctival cytokine expression profile.: Eligible DES patients were randomized into an EA group (EAG) or an acupuncture group (AG). The ocular surface disease index (OSDI), amount of tear production, and tear film break-up time (BUT) were observed to evaluate the efficacy. Conjunctival cells were collected from both effective and invalid cases to observe the expressions of cytokines by protein microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional cluster and signaling pathway analysis of the differentially expressed proteins. Enzyme-linked immunosorbent assay (ELISA) was used to verify the specific differential proteins.: After treatment, OSDI dropped and BUT extended in both groups, and the tear production increased only in the EAG (all

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PMID: 

Molecules. 2019 Sep 30 ;24(19). Epub 2019 Sep 30. PMID: 31574930

Abstract Title: 

Bacopasides I and II Act in Synergy to Inhibit the Growth, Migration and Invasion of Breast Cancer Cell Lines.

Abstract: 

Bacopaside (bac) I and II are triterpene saponins purified from the medicinal herb. Previously, we showed that bac II reduced endothelial cell migration and tube formation and induced apoptosis in colorectal cancer cell lines. The aim of the current study was to examine the effects of treatment with combined doses of bac I and bac II using four cell lines representative of the breast cancer subtypes: triple negative (MDA-MB-231), estrogen receptor positive (T47D and MCF7) and human epidermal growth factor receptor 2 (HER2) positive (BT-474). Drug treatment outcome measures included cell viability, proliferation, cell cycle, apoptosis, migration, and invasion assays. Relationships were analysed by one- and two-way analysis of variance with Bonferroni post-hoc analysis. Combined doses of bac I and bac II, each below their half maximal inhibitory concentration (IC), were synergistic and reduced the viability and proliferation of the four breast cancer cell lines. Cell loss occurred at the highest dose combinations and was associated with G2/M arrest and apoptosis. Migration in the scratch wound assay was significantly reduced at apoptosis-inducing combinations, but also at non-cytotoxic combinations, for MDA-MB-231 and T47D (

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