PMID: 

Oxid Med Cell Longev. 2018 ;2018:5438179. Epub 2018 Jun 6. PMID: 29977456

Abstract Title: 

Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway.

Abstract: 

Sulforaphane (SFN), a compound derived from cruciferous vegetables that has been shown to be safe and nontoxic, with minimal/no side effects, has been extensively studied due to its numerous bioactivities, such as anticancer and antioxidant activities. SFN exerts its anticancer effects by modulating key signaling pathways and genes involved in the induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis. SFN also upregulates a series of cytoprotective genes by activating nuclear factor erythroid-2- (NF-E2-) related factor 2 (Nrf2), a critical transcription factor activated in response to oxidative stress; Nrf2 activation is also involved in the cancer-preventive effects of SFN. Accumulating evidence supports that epigenetic modification is an important factor in carcinogenesis and cancer progression, as epigenetic alterations often contribute to the inhibition of tumor-suppressor genes and the activation of oncogenes, which enables cells to acquire cancer-promoting properties. Studies on the mechanisms underlying the anticancer effects of SFN have shown that SFN can reverse such epigenetic alterations in cancers by targeting DNA methyltransferases (DNMTs), histone deacetyltransferases (HDACs), and noncoding RNAs. Therefore, in this review, we will discuss the anticancer activities of SFN and its mechanisms, with a particular emphasis on epigenetic modifications, including epigenetic reactivation of Nrf2.

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PMID: 

Pharm Biol. 2019 Dec ;57(1):392-402. PMID: 31188689

Abstract Title: 

Fermented driedpeel extracts exert anti-inflammatory activities in LPS-induced RAW264.7 macrophages and improve skin moisturizing efficacy in immortalized human HaCaT keratinocytes.

Abstract: 

Markovich (Rutaceae) peel is known to contain high concentrations of flavonoids and exerts pharmacological effects on antioxidant, anti-inflammation, allergies, diabetes and viral infections.Very little is known about potential activity of fermented driedpeel extracts (FCU) using, as well as its mechanism of action. We investigated the effects of FCU on the anti-inflammatory activities in murine macrophages and moisturizing effects in human keratinocytes.We isolated thefrom Cheonggukjang and FCU using theseto prepare samples. The cells were pre-treated with various extracts for 2 h and then induced with LPS for 22 h. We determined the NO assay, TNF-α, IL-6 and PGEin RAW 264.7 ells. The expression of SPT and Filaggrin by FCU treatment was measured in HaCaT cells.We found that two types of FCU highly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells (21.9 and 15.4% reduction). FCU inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNAs in a concentration-dependent manner. TNF-α (59 and 30.9% reduction), IL-6 (39.1 and 65.6% reduction), and PGEsecretion (78.6 and 82.5% reduction) were suppressed by FCU in LPS-stimulated macrophages. Furthermore, FCU can induce the production of hyaluronic acid (38 and 38.9% induction) and expression of Filaggrin and SPT in HaCaT keratinocyte cells.FCU potentially inhibits inflammation, improves skin moisturizing efficacy, and it may be a therapeutic candidate for the treatment of inflammation and dry skin.

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PMID: 

J Agric Food Chem. 2019 Jul 18. Epub 2019 Jul 18. PMID: 31318199

Abstract Title: 

Anti-inflammatory effect of Pomelo peel and its bioactive coumarins.

Abstract: 

Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world and its peels are sometimes used for the treatment of cough, abdominal pain and indigestion in China. However, the peel is discarded after fruits consumption in most cases and its chemical constituents and biological activities haven't been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema, carrageenan-induced paw edema in mice, and the production of inflammatory cytokines (IL-1β, PGE2, TNF-α) in lipopolysaccharide (LPS) induced RAW 264.7 cells. Results indicated that methanolic extract (ME), ethyl acetate fraction (EAC) and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan respectively in vivo. Furthermore, 18 coumarins inhibited inflammatory factors secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone (DXM). In summary, peel of C. grandis showed an anti-inflammatory effect, and coumarins compounds were responsible for the regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.

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PMID: 

Food Funct. 2019 Jun 19 ;10(6):3727-3737. PMID: 31169845

Abstract Title: 

Effect of citrus peel extracts on the cellular quiescence of prostate cancer cells.

Abstract: 

The re-entry of quiescent cancer cells to the cell cycle plays a key role in cancer recurrence, which can pose a high risk after primary treatment. Citrus peel extracts (CPEs) contain compounds that can potentially impair tumour growth; however the mechanism of action and effects on cell cycle regulation remain unclear. In this study, the capacity of an ethyl acetate : hexane extract (CPE/hexane) and water extract (CPE/water) to modulate the cell cycle re-entry of quiescent (PC-3 and LNCaP) prostate cancer cells was tested in an in vitro culture system. Cell cycle analysis showed that the quiescent PC-3 and LNCaP cancer cells in the presence of CPE/water were impaired in their ability to enter the S phase where only 2-3% reduction of G0/G1 cells was noted compared to 12-18% reduction of control cells. In contrast, the CPE/hexane did not show any cell cycle inhibition activity in both cell lines. A low DNA synthesis rate and weak apoptosis were observed in quiescent cancer cells treated with CPEs. Hesperidin and narirutin, the predominant flavonoids found in citrus fruits, were not responsible for the observed biological activity, implicating alternative bioactive compounds. Notably, citric acid was identified as one of the compounds present in CPEs that acts as a cell cycle re-entry inhibitor. Citric acid exhibited a higher cell toxicity effect on PC-3 prostate cancer cells than non-cancerous RWPE-1 prostate cells, suggesting specific benefits for cancer treatment. In conclusion, CPE containing citric acid together with various bioactive compounds may be used as a chemopreventive agent for post-therapy cancer patients.

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PMID: 

Medicina (Kaunas). 2019 Jul 12 ;55(7). Epub 2019 Jul 12. PMID: 31336963

Abstract Title: 

Radioprotective Effect of Hesperidin: A Systematic Review.

Abstract: 

: Ionizing radiation (IR) has been of immense benefit to man, especially for medical purposes (diagnostic imaging and radiotherapy). However, the risks of toxicity in healthy normal cells, leading to cellular damage as well as early and late side effects, have been major drawbacks. The aim of this study was to evaluate the radioprotective effect of hesperidin against IR-induced damage.The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were applied in reporting this study. A search was conducted using the electronic databases PubMed, Scopus, Embase, Google Scholar, and http://www.ClinicalTrials.gov for information about completed or ongoing clinical trials.From our search results, 24 studies involving rats, mice, and cultured human and animal cells were included. An experimental case-control design was used in all studies. The studies showed that the administration of hesperidin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, it increased 30-day and 60-day survival rates and protected against DNA damage. The best radioprotection was obtained when hesperidin was administered before irradiation.The results of the included studies support the antioxidant, anti-inflammatory, and antiapoptotic abilities of hesperidin as a potential radioprotective agent against IR-induced damage. We recommend future clinical trials for more insights.

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PMID: 

Molecules. 2018 Jul 19 ;23(7). Epub 2018 Jul 19. PMID: 30029485

Abstract Title: 

Protective Mechanism of Sulforaphane on Cadmium-Induced Sertoli Cell Injury in Mice Testis via Nrf2/ARE Signaling Pathway.

Abstract: 

The present study evaluated the mechanism underlying the protective effect of sulforaphane (SFN) on cadmium (Cd)-induced Sertoli cell (TM4 cells) injury in mice. The apoptosis rate of cells in each group was detected by flow cytometry. It was determined the effect of SFN on the expression of downstream molecular targets of Nrf2/ARE axis and on the lipid peroxide content. The related genes involved in the nuclear factor E2-related factor 2(Nrf2)/antioxidant response element (ARE) signaling pathway were evaluated by RT-PCR; for example, the mRNA expression levels of Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase (GSH-Px), quinone oxidoreductase 1 (NQO1), andγ-glutamylcysteine synthetase (γ-GCS), while the protein expression levels were assessed by Western blot. Our results showed that the mRNA and protein expression levels of Nrf2, HO-1, NQO1, GSH-Px, and γ-GCS were increased in various degree when the Sertoli cells were to added different concentrations of SFN. Our results also showed that SFN reduced the apoptosis rate, increased the activity of T-SOD, inhibited the increase of the MDA content caused by Cd. Meanwhile, SFN could increase the mRNA and protein expression levels of Nrf2, HO-1 and NQO1 and reduced the mRNA and protein expressionlevels of GSH-Px and γ-GCS caused by Cd in Sertoli cells (

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PMID: 

Cell Tissue Res. 2018 Dec ;374(3):629-641. Epub 2018 Jul 21. PMID: 30032437

Abstract Title: 

Sulforaphane protects granulosa cells against oxidative stress via activation of NRF2-ARE pathway.

Abstract: 

Sulforaphane (SFN) has been considered as an indirect antioxidant and potential inducer of the Nrf2-ARE pathway. This study was conducted to investigate the protective role of SFN against oxidative stress in bovine granulosa cells (GCs). GCs were collected from antral follicles (4-8 mm) and cultured according to the experimental design where group 1 = control, group 2 = treated with SFN, group 3 = treated with hydrogen peroxide (HO), group 4 = pretreated with SFN and then with HO(protective) and group 5 = treated with HOfollowed by SFN treatment (rescuing). Results showed that SFN pretreatment significantly increases cell viability and reduces cytotoxicity in GCs under oxidative stress. Following HOexposure, expression of NRF2 was found to be significantly increased (p 

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PMID: 

Toxicol Mech Methods. 2019 Jul 25:1-32. Epub 2019 Jul 25. PMID: 31345080

Abstract Title: 

Hesperidin, a citrus flavonoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats.

Abstract: 

The present study was investigated the protective effect of hesperidin on carbohydrate metabolizing enzymes in streptozotocin induced diabetic rats. Hesperidin was administered to streptozotocin-induced (40 mg/kg b.w) diabetic rats at different dosages of (25, 50, 100 mg/kg b.w.) respectively for 30 days to evaluate its effect on fasting plasma glucose, insulin, glycosylated hemoglobin, hemoglobin and carbohydrate metabolic enzymes. The plasma glucose levels were significantly reduced in a dose-dependent manner in hesperdin treated group of rats when compared to the diabetic control rats. In addition, concomitant increase in hemoglobin and insulin levels and a decrease in glycosylated hemoglobin were observed in treated group of rats. The activities of the hepatic key enzymes of carbohydratemetabolism such as hexokinase and glucose-6-phosphate dehydrogenase were significantly increased whereas, glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly decreased. Furthermore, Hesperidin administration prevented the loss in body weight and improved the glycogen content inthe hepatic tissue of diabetic animals by reinstating the activities of glycogen synthase and glycogen phosphorylase. These results showed that hesperidin has potential antihyperglycemic activity in streptozotocin- induced diabetic rats. This was further supported by the histological studies of pancreas and liver.

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PMID: 

Cells Tissues Organs. 2018 ;206(1-2):46-53. Epub 2018 Jul 24. PMID: 30041241

Abstract Title: 

Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells.

Abstract: 

BACKGROUND: A high expression of prostaglandin E2 (PGE2) is found in colorectal cancer. Therefore, blocking of PGE2 generation has been identified as a promising approach for anticancer therapy. Sulforaphane (SFN), an isothiocyanate derived from glucosinolate, is used as the antioxidant and anticancer agents.METHODS: HT-29 cells were treated with various concentrations of SFN and compared to untreated cells for the expression of microsomal prostaglandin E synthase-1 (mPGES-1), cyclooxygenase 2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 and MMP-9 at the mRNA level. The PGE2 level was measured by ELISA assay. Apoptosis was evaluated by the proportion of sub-G1 cells. The activity of caspase-3 was determined using an enzymatic assay. HT-29 cell migration was assessed using a scratch test.RESULTS: SFN preconditioning decreased the expression of COX-2, mPGES-1, HIF-1, VEGF, CXCR4, MMP-2, and MMP-9. An apoptotic effect of SFN was preceded by the activation of caspase-3 as well as accumulation of cells in the sub-G1 phase of the cell cycle. SFN decreased PGE2 generation and inhibited the in vitro motility/wound-healing activity of HT-29 cells.CONCLUSIONS: SFN anticancer effects are associated with antiproliferative, antiangiogenic, and antimetastatic activities arising from the downregulation of the COX-2/ mPGES-1 axis.

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PMID: 

Plants (Basel). 2019 Jul 25 ;8(8). Epub 2019 Jul 25. PMID: 31349715

Abstract Title: 

Quercetin Mediated Salt Tolerance in Tomato through the Enhancement of Plant Antioxidant Defense and Glyoxalase Systems.

Abstract: 

Quercetin (Qu) is a strong antioxidant among the phenolic compounds having physiological and biochemical roles in plants. Hence, we have studied the Qu evolved protection against salinity in tomato (L.). Salinity caused ionic toxicity by increasing Nacontent in seedlings along with nutritional starvation of K, Ca, and Mg. While osmotic stress was detected by higher free proline (Pro) content and lower leaf relative water content (LRWC) in salt-stressed seedlings. Salt toxicity also induced higher HOgeneration, malondialdehyde (MDA) content and lipoxygenase (LOX) activity as a sign of oxidative stress. Tomato seedlings suffered from methylglyoxal (MG) toxicity, degradation of chlorophyll, along with lower biomass accumulation and growth due to salt exposure. However, Qu application under salinity resulted in lower Na/Kdue to reduced Nacontent, higher LRWC, increased Pro, and reduction of HOand MDA content, and LOX activity, which indicated alleviation of ionic, osmotic, and oxidative stress respectively. Quercetin caused oxidative stress, lessening through the strengthening of both enzymatic and non-enzymatic antioxidants. In addition, Qu increased glutathione-transferase activity in salt-invaded seedlings, which might be stimulated reactive oxygen species (ROS) scavenging along with higher GSH content. As a result, toxic MG was detoxified in Qu supplemented salt-stressed seedlings by increasing both Gly I and Gly II activities. Moreover, Qu insisted on better plant growth and photosynthetic pigments synthesis in saline or without saline media. Therefore, exogenous applied Qu may become an important actor to minimize salt-induced toxicity in crops.

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