Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2015 Volume 12 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2015 Volume 12 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes

  • Authors:
    • Eun‑Ok Choi
    • Cheol Park
    • Soon Shik Shin
    • Eun‑Ju Cho
    • Byung Woo Kim
    • Jin Ah Hwang
    • Hye‑Jin Hwang
    • Yung Hyun Choi
  • View Affiliations / Copyright

    Affiliations: Department of Food and Nutrition, Busan National University, Busan 609‑735, Republic of Korea, Department of Molecular Biology, Dongeui University, Busan 614‑714, Republic of Korea, Department of Formula Sciences, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Life Science and Biotechnology, Dongeui University, Busan 614‑714, Republic of Korea, Department of Food and Nutrition, Myongji University, Yongin 449‑728, Republic of Korea, Anti‑Aging Research Center, Dongeui University, Busan 614‑714, Republic of Korea
  • Pages: 1314-1320
    |
    Published online on: March 10, 2015
       https://doi.org/10.3892/mmr.2015.3463
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Zanthoxylum schinifolium is widely used as a food flavoring in east Asia. Although this plant has also been used in traditional oriental medicine for the treatment of the common cold, toothache, stomach ache, diarrhea and jaundice, its anti‑obesity activity remains to be elucidated. The present study investigated the effects of ethanol extract from the leaves of Z. schinifolium (EEZS) on adipocyte differentiation, and its underlying mechanism, in 3T3‑L1 pre‑adipocytes. The results demonstrated that EEZS effectively suppressed intracellular lipid accumulation at non‑toxic concentrations, and was associated with the downregulation of several adipocyte‑specific transcription factors, including peroxisome proliferation‑activity receptor γ (PPARγ), CCAAT/enhancer binding protein (C/EBP)α and C/EBPβ, in a concentration‑dependent manner. Furthermore, it was observed that EEZS markedly inactivated the extracellular signal‑regulated protein kinase (ERK) and phosphatidylinositide 3‑kinase (PI3K)/Akt pathways, which act upstream of PPARγ and C/EBPs in adipogenesis. These results suggested that EEZS inhibited lipid accumulation by downregulating the major transcription factors involved in the pathway of adipogenesis, including PPARγ, C/EBPα and C/EBPβ, via regulation of the ERK and PI3K/Akt signaling pathways in 3T3‑L1 adipocyte differentiation. This indicated the potential use of EEZS as an anti‑obesity agent.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Dorresteijn JA, Visseren FL and Spiering W: Mechanisms linking obesity to hypertension. Obes Rev. 13:17–26. 2012. View Article : Google Scholar

2 

Franssen R, Monajemi H, Stroes ES and Kastelein JJ: Obesity and dyslipidemia. Med Clin North Am. 95:893–902. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Rocha VZ and Libby P: Obesity, inflammation and atherosclerosis. Nat Rev Cardiol. 6:399–409. 2009. View Article : Google Scholar : PubMed/NCBI

4 

McCarthy MI: Genomics, type 2 diabetes and obesity. N Engl J Med. 363:2339–2350. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Speliotes EK: Genetics of common obesity and nonalcoholic fatty liver disease. Gastroenterology. 136:1492–1495. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Pischon N, Heng N, Bernimoulin JP, Kleber BM, Willich SN and Pischon T: Obesity, infammation and periodontal disease. J Dent Res. 86:400–409. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Lloyd CM and Saglani S: Eosinophils in the spotlight: Finding the link between obesity and asthma. Nat Med. 19:976–977. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Tzotzas T, Evangelou P and Kiortsis DN: Obesity, weight loss and conditional cardiovascular risk factors. Obes Rev. 12:e282–e289. 2011. View Article : Google Scholar

9 

Thompson D and Wolf AM: The medical-care cost burden of obesity. Obes Rev. 2:189–197. 2001. View Article : Google Scholar

10 

Dalla Vecchia CF, Susin C, Rösing CK, Oppermann RV and Albandar JM: Overweight and obesity as risk indicators for periodontitis in adults. J Periodontol. 76:1721–1728. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Zimmet P, Alberti KG and Shaw J: Global and societal implications of the diabetes epidemic. Nature. 414:782–787. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Bray GA and Tartaglia LA: Medicinal strategies in the treatment of obesity. Nature. 404:672–677. 2000.PubMed/NCBI

13 

Tam CS, Lecoultre V and Ravussin E: Novel strategy for the use of leptin for obesity therapy. Expert Opin Biol Ther. 11:1677–1685. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Rosen ED: The transcriptional basis of adipocyte development. Prostaglandins Leukot Essent Fatty Acids. 73:31–34. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Soukas A, Socci ND, Saatkamp BD, Novelli S and Friedman JM: Distinct transcriptional profiles of adipogenesis in vivo and in vitro. J Biol Chem. 276:34167–34174. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Prusty D, Park BH, Davis KE and Farmer SR: Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem. 277:46226–46232. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Rosen ED and MacDougald OA: Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 7:885–896. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Smith PJ, Wise LS, Berkowitz R, Wan C and Rubin CS: Insulin–like growth factor–I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem. 263:9402–9408. 1988.PubMed/NCBI

19 

Bost F, Aouadi M, Caron L and Binétruy B: The role of MAPKs in adipocyte differentiation and obesity. Biochimie. 87:51–56. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Magun R, Burgering BM, Coffer PJ, Pardasani D, Lin Y, Chabot J and Sorisky A: Expression of a constitutively activated form of protein kinase B (c-Akt) in 3T3-L1 preadipose cells causes spontaneous differentiation. Endocrinology. 137:3590–3593. 1996.PubMed/NCBI

21 

Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG and Hay N: Dwarfsm, impaired skin development, skeletal muscle atrophy, delayed bone development and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 17:1352–1365. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Jo YS, Huong DT, Bae K, Lee MK and Kim YH: Monoamine oxidase inhibitory coumarin from Zanthoxylum schinifolium. Planta Med. 68:84–85. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Paik SY, Koh KH, Beak SM, Paek SH and Kim JA: The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species. Biol Pharm Bull. 28:802–807. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Tsai IL, Lin WY, Teng CM, Ishikawa T, Doong SL, Huang MW, Chen YC and Chen IS: Coumarins and antiplatelet constituents from the root bark of Zanthoxylum schinifolium. Planta Med. 66:618–623. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Chen IS, Lin YC, Tsai IL, Teng CM, Ko FN, Ishikawa T and Ishii H: Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry. 39:1091–1097. 1995. View Article : Google Scholar : PubMed/NCBI

26 

Cao LH, Lee YJ, Kang DG, Kim JS and Lee HS: Effect of Zanthoxylum schinifolium on TNF-alpha-induced vascular inflammation in human umbilical vein endothelial cells. Vascul Pharmacol. 50:200–207. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Li W, Sun YN, Yan XT, Yang SY, Kim EJ, Kang HK and Kim YH: Coumarins and lignans from Zanthoxylum schinifolium and their anticancer activities. J Agric Food Chem. 61:10730–10740. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Jun DY, Kim JS, Park HS, Han CR, Fang Z, Woo MH, Rhee IK and Kim YH: Apoptogenic activity of auraptene of Zanthoxylum schinifolium toward human acute leukemia Jurkat T cells is associated with ER stress-mediated caspase-8 activation that stimulates mitochondria-dependent or -independent caspase cascade. Carcinogenesis. 28:1303–1313. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Kim MY, Kim DH and Do MS: B-cell-activating factor is a regulator of adipokines and a possible mediator between adipocytes and macrophages. Exp Mol Med. 45:e42013. View Article : Google Scholar : PubMed/NCBI

30 

Rhyu J, Kim MS, You MK, Bang MA and Kim HA: Pear pomace water extract inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Nutr Res Pract. 8:33–39. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Kopelman PG: Obesity as a medical problem. Nature. 404:635–643. 2000.PubMed/NCBI

32 

Ntambi JM and Young-Cheul K: Adipocyte differentiation and gene expression. J Nutr. 130:3122S–3126S. 2000.

33 

Tong Q and Hotamisligil GS: Molecular mechanisms of adipocyte differentiation. Rev Endocr Metab Disord. 2:349–355. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Cornelius P, MacDougald OA and Lane MD: Regulation of adipocyte development. Annu Rev Nutr. 14:99–129. 1994. View Article : Google Scholar : PubMed/NCBI

35 

Kohn AD, Summers SA, Birnbaum MJ and Roth RA: Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem. 271:31372–31378. 1996. View Article : Google Scholar : PubMed/NCBI

36 

Uto-Kondo H, Ohmori R, Kiyose C, Kishimoto Y, Saito H, Igarashi O and Kondo K: Tocotrienol suppresses adipocyte differentiation and Akt phosphorylation in 3T3-L1 preadipocytes. J Nutr. 139:51–57. 2009. View Article : Google Scholar

37 

Zhang HH, Huang J, Düvel K, Boback B, Wu S, Squillace RM, Wu CL and Manning BD: Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS One. 4:e61892009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Choi EO, Park C, Shin SS, Cho EJ, Kim BW, Hwang JA, Hwang HJ and Choi YH: Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes. Mol Med Rep 12: 1314-1320, 2015.
APA
Choi, E., Park, C., Shin, S.S., Cho, E., Kim, B.W., Hwang, J.A. ... Choi, Y.H. (2015). Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes. Molecular Medicine Reports, 12, 1314-1320. https://doi.org/10.3892/mmr.2015.3463
MLA
Choi, E., Park, C., Shin, S. S., Cho, E., Kim, B. W., Hwang, J. A., Hwang, H., Choi, Y. H."Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes". Molecular Medicine Reports 12.1 (2015): 1314-1320.
Chicago
Choi, E., Park, C., Shin, S. S., Cho, E., Kim, B. W., Hwang, J. A., Hwang, H., Choi, Y. H."Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes". Molecular Medicine Reports 12, no. 1 (2015): 1314-1320. https://doi.org/10.3892/mmr.2015.3463
Copy and paste a formatted citation
x
Spandidos Publications style
Choi EO, Park C, Shin SS, Cho EJ, Kim BW, Hwang JA, Hwang HJ and Choi YH: Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes. Mol Med Rep 12: 1314-1320, 2015.
APA
Choi, E., Park, C., Shin, S.S., Cho, E., Kim, B.W., Hwang, J.A. ... Choi, Y.H. (2015). Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes. Molecular Medicine Reports, 12, 1314-1320. https://doi.org/10.3892/mmr.2015.3463
MLA
Choi, E., Park, C., Shin, S. S., Cho, E., Kim, B. W., Hwang, J. A., Hwang, H., Choi, Y. H."Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes". Molecular Medicine Reports 12.1 (2015): 1314-1320.
Chicago
Choi, E., Park, C., Shin, S. S., Cho, E., Kim, B. W., Hwang, J. A., Hwang, H., Choi, Y. H."Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes". Molecular Medicine Reports 12, no. 1 (2015): 1314-1320. https://doi.org/10.3892/mmr.2015.3463
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team