Skip to main content

Advertisement

SpringerLink
Log in

Ginsenoside Rb1 Upregulating AQP5 Protein Expression and Alleviating Salivary Secretion Impairment in Ovariectomized Sjögren’s Syndrome Mice

  • Published:
Chemical Research in Chinese Universities Aims and scope

Abstract

Sjögren’s syndrome(SS) is an autoimmune disease characterized as the impairment of salivary secretion mediated by abnormal aquaporin 5(AQP5). Here we used AQP5 promoter as the target to screen the effective components from natural drugs. Panax quinquefolius and its specific ingredient, Rb1, were identified to increase the AQP5 transcriptional activity and AQP5 expression. Then we investigated the possibility of Rb1 binding to sex hormone receptors and demonstrated that Rb1 bound specifically to estrogen receptor alpha(ERα), but not to androgen receptor. Next, we found that ERα overexpression magnified the effect of Rb1 induced AQP5 transcription, and the silence of ERα blocked this effect, demonstrating that Rb1 activated AQP5 transcription via ERα pathway. Importantly, we constructed SS mouse model and investigated the effects of Rb1 on salivary secretion in vivo. SS mice exhibited significant impairment in salivary secretion and decreased AQP5 expression in the submandibular gland. Intriguingly, SS mice administered with Rb1 exhibited dramatically increased salivary secretion, followed by decreased diary water consumption. In particular, Rb1 up-regulated AQP5 expression localized in the submandibular gland, almost similar to the SS mice administered with estrogen. Our data demonstrated that Rb1 bound with ERα to up-regulate AQP5 to increase saliva secretion, thus functioned as a potential natural phytoestrogen for the therapy of salivary secretion impairment in SS patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Patel R., Shahane A., Clin. Epidemiol., 2014, 6, 247

    PubMed  PubMed Central  Google Scholar 

  2. Zhang N. Z., Shi C. S., Yao Q. P., Pan G. X., Wang L. L., Wen Z. X., Li X. C., Dong Y., J. Rheumatology, 1995, 22, 659

    CAS  Google Scholar 

  3. Zhang W., Feng S., Yan S., Zhao Y., Li M., Sun J., Zhang F. C., Cui Q., Dong Y., J. Rheumatology, 2010, 49, 571

    Article  Google Scholar 

  4. Castro I., Sepúlveda D., Cortés J., Quest A. F., Barrera M. J., Bahamondes V., Aguilera S., Urzúa U., Alliende C., Molina C., Autoimmun. Rev., 2013, 12, 567

    Article  CAS  PubMed  Google Scholar 

  5. Steinfeld S., Cogan E., King L. S., Agre P., Kiss R., Delporte C., Lab. Investig., 2001, 81, 143

    Article  CAS  PubMed  Google Scholar 

  6. Enger T. B., Aure M. H., Jensen J. L., Galtung H. K., Acta Odontol. Scand., 2014, 72, 549

    Article  CAS  PubMed  Google Scholar 

  7. Yoshimura S., Nakamura H., Horai Y., Nakajima H., Shiraishi H., Hayashi T., Takahashi T., Kawakami A., Mod. Rheumatol., 2015, 16, 1

    Google Scholar 

  8. Funaki H., Yamamoto T., Koyama Y., Kondo D., Yaoita E., Kawasaki K., Kobayashi H., Sawaguchi S., Abe H., Kihara I., Am. J. Physiol., 1998, 275, 1151

    Article  Google Scholar 

  9. Iizuka T., Suzuki T., Nakano K., Sueki H., J. Dermatol., 2012, 39, 344

    Article  PubMed  Google Scholar 

  10. Inoue R., Sohara E., Rai T., Satoh T., Yokozeki H., Sasaki S., Uchida S., J. Dermatol., 2013, 70, 26

    CAS  Google Scholar 

  11. Cho G., Bragiel A. M., Wang D., Pieczonka T. D., Skowronski M. T., Shono M., Nielsen S., Ishikawa Y., Biochim. Biophys. Acta, 2015, 1850, 784

    Article  CAS  PubMed  Google Scholar 

  12. Matsuzaki T., Susa T., Shimizu K., Sawai N., Suzuki T., Aoki T., Yokoo S., Takata K., Acta Histochem. Cytochem., 2012, 45, 251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Konttinen Y. T., Tensing E. K., Laine M., Porola P., Törnwall J., Hukkanen M., J. Rheumatology, 2005, 32, 1071

    CAS  Google Scholar 

  14. Konttinen Y. T., Stegajev V., Al-Samadi A., Porola P., Hietanen J., Ainola M., J. Steroid. Biochem. Mol. Biol., 2015, 145, 237

    Article  CAS  PubMed  Google Scholar 

  15. Beeson P. B., Am. J. Med., 1994, 96, 457

    Article  CAS  PubMed  Google Scholar 

  16. Tsinti M., Kassi E., Korkolopoulou P., Kapsogeorgou E., Moutsatsou P., Patsouris E., Manoussakis M. N., Eur. J. Oral. Sci., 2009, 117, 498

    Article  CAS  PubMed  Google Scholar 

  17. Eliasson L., Carlén A., Laine M., Birkhed D., Arch. Oral. Biol., 2003, 48, 511

    Article  CAS  PubMed  Google Scholar 

  18. Shan L. J., Gu J. H., World Journal of Integrated Tranditional and Western Medicine, 2015, 6, 874

    Google Scholar 

  19. Liu J. H., Burdette J. E., Xu H., Gu C., van Breemen R. B., Bhat K. P., Booth N., Constantinou A. I., Pezzuto J. M., Fong H. H., Farnsworth N. R., Bolton J. L., J. Agric. Food. Chem., 2001, 49, 2472

    Article  CAS  PubMed  Google Scholar 

  20. Greenspan J. S., Daniels T. E., Talal N., Sylvester R. A., Oral. Surg. Oral. Med. Oral. Pathol., 1974, 37, 217

    Article  CAS  PubMed  Google Scholar 

  21. Li L., Xie L. J., Wang G. M., Xu F. F., Guo C. B., Wang H. Y., Cao Z. Q., J. Gins. Res., 2018, 30, 11

    Google Scholar 

  22. Baer A. N., Walitt B., Rheum. Dis. Clin. North. Am., 2018, 44, 419

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jensen S. B., Vissink A., Oral. Maxillofac. Surg. Clin. North. Am., 2014, 26, 35

    Article  PubMed  Google Scholar 

  24. Castro I., Aguilera S., Brockhausen I., Alliende C., Quest A. F., Molina C., Urzúa U., Mandel U., Bahamondes V., Barrera M. J., J. Rheumatology, 2012, 51, 482

    Article  CAS  Google Scholar 

  25. Chen X., Wu H., Wei W., Clin. Rheumatol., 2018, 37, 1743

    Article  PubMed  Google Scholar 

  26. Kroese F. G. M., Haacke E. A., Bombardieri M., Clin. Exp. Rheumatol., 2018, 36, 222

    PubMed  Google Scholar 

  27. Xiao L., Ng T. B., Feng Y. B., Yao T., Wong J. H., Yao R. M., Li L., Mo F. Z., Xiao Y., Shaw P. C., Li Z. M., Sze S. C., Zhang K. Y., Phytomedicine, 2011, 15, 194

    Article  CAS  Google Scholar 

  28. Tomoko I., Eiji N., Kasumi T., Katsumi H., Takeshi U., Yoshiki N., Joji S., J. Oral. Sci., 2018, 60, 212

    Article  CAS  Google Scholar 

  29. Aure M. H., Larsen H. S., Ruus A. K., Galtung H. K., J. Mol. Histol., 2011, 42, 401

    Article  CAS  PubMed  Google Scholar 

  30. Paula F. D., Teshima T. H. N., Hsieh R., Souza M. M., Coutinho-Camillo C. M., Nico M. M. S., Lourenco S. V. J. Mol. Histol., 2017, 48, 329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ma T., Song Y., Gillespie A., Carlson E. J., Epstein C. J., Verkman A. S., J. Biol. Chem., 1999, 274, 20071

    Article  CAS  PubMed  Google Scholar 

  32. Krane C. M., Melvin J. E., Nguyen H. V., Richardson L., Towne J. E., Doetschman T., Menon A. G., J. Biol. Chem., 2001, 276, 23413

    Article  CAS  PubMed  Google Scholar 

  33. Mavragani C. P., Fragoulis G. E., Moutsopoulos H. M., J. Autoimmun., 2012, 39, 354

    Article  CAS  PubMed  Google Scholar 

  34. Csányi A., Bóta J., Falkay G., Gáspár R., Ducza E., Int. J. Mol. Sci., 2016, 17, 1300

    Article  CAS  PubMed Central  Google Scholar 

  35. Hashimoto R., Yu J., Koizumi H., Ouchi Y., Okabe T., Evid. Based. Compl. Alternat. Med., 2012, 4, 693717

    Google Scholar 

  36. Hao K., Gong P., Sun S. Q., Hao H. P., Wang G. J., Dai Y., Chen Y. C., Liang Y., Xie L., Li F. Y., Li H. Y., Eur. J. Pharm. Sci., 2011, 44, 117

    Article  CAS  PubMed  Google Scholar 

  37. Kobayashi M., Takahashi E., Miyagawa S., Watanabe H., Iguchi T., Genes Cells, 2006, 11, 1133

    Article  CAS  PubMed  Google Scholar 

  38. Lodde B. M., Mineshiba F., Kok M. R., Wang J., Zheng C., Schmidt M., Cotrim A. P., Kriete M., Tak P. P., Baum B. J., Oral. Dis., 2006, 12, 566

    Article  CAS  PubMed  Google Scholar 

  39. Cong X., Zhang X. M., Zhang Y., Wei T., Wu L. L., BBA-Mol. Basis. Dis., 2018, 1864, 3154

    Article  CAS  Google Scholar 

  40. Nayar S., Campos J., Buckley C. D., Allen R. A., Fahy W. A., Payne A., Barone F., Ann. Rheum. Dis., 2016, 75, A58.2

    Article  Google Scholar 

  41. Liu S., Niu K., Da Y., Liu Y., Zhang J., Wang W., Zhang Y., Jiang H., Wang K., Bai W., Qin L., Jia J., Biomed. Pharmacther., 2018, 97, 1438

    Article  CAS  Google Scholar 

  42. Stern M. E., Gao J., Schwalb T. A., Ngo M., Tieu D. D., Chan C. C., Reis B. L., Whitcup S. M., Thompson D., Smith J. A., Invest. Ophthalmol. Vis. Sci., 2002, 43, 2609

    PubMed  Google Scholar 

  43. Arakaki R., Ishimaru N., Saito I., Kobayashi M., Yasui N., Sumida T., Hayashi Y., Arthritis. Rheum., 2003, 48, 3603

    Article  CAS  PubMed  Google Scholar 

  44. Kassan S. S., Thomas T. L., Moutsopoulos H. M., Hoover R., Kimberly R. P., Budman D. R., Costa J., Decker J. L., Chused T. M., Ann. Intern. Med., 1978, 89, 888

    Article  CAS  PubMed  Google Scholar 

  45. Theander E., Henriksson G., Ljungberg O., Mandl T., Manthorpe R., Jacobsson L. T., Ann. Rheum. Dis., 2006, 65, 796

    Article  CAS  PubMed  Google Scholar 

  46. Miao H. H., Zhang Y., Ding G. N., Hong F. X., Dong P., Tian M., Biomed. Environ. Sci., 2017, 30, 363

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dental Hospital, Jilin University, Changchun, 130021, P. R. China

    Xi He, Liu Yang, Xintong Liu, Wei Wei, Ce Shi, Baoquan Li & Jiang Li

Authors
  1. Xi He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xintong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ce Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Baoquan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiang Li.

Additional information

Supported by the Fund of Science and Technology Department of Jilin Provine, China (No. 20170204009YY), the Fund of the Science & Technology Department of Changchun, China (No. 17YJ001), the Foundation of the Ministry of Science and Technology of China (No. 2016YFE0128500), and the Fund of the Development and Reform Commission of Jilin Province, China (No. 2016C048-3).

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, X., Yang, L., Liu, X. et al. Ginsenoside Rb1 Upregulating AQP5 Protein Expression and Alleviating Salivary Secretion Impairment in Ovariectomized Sjögren’s Syndrome Mice. Chem. Res. Chin. Univ. 35, 418–426 (2019). https://doi.org/10.1007/s40242-019-9056-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40242-019-9056-y

Keywords

Search

Navigation