Skip to main content
SpringerLink
Log in

Quercetin-3-O-β-d-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Cellular senescence is known to contribute to tissue aging, a variety of age-related diseases, tissue regeneration, and cancer. Therefore, aging intervention might be useful for prevention of aging as well as age-related disease. In this study, we investigated compounds from Polygonum aviculare to determine if they inhibited cellular senescence in human primary cells, human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). Ten compounds from P. aviculare were purified and their inhibitory effects on adriamycin-induced cellular senescence were measured by observing senescence-associated β-galactosidase (SA-β-gal) activity and reactive oxygen species. Among them, compound 9 (quercetin-3-O-β-d-glucuronide) showed inhibitory effects against cellular senescence in HDFs and HUVECs treated with adriamycin. Additionally, compound 9 rescued replicative senescence in HDFs and HUVECs. These data imply that compound 9 represses cellular senescence in human primary cells and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or aging-associated diseases.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • An, R.-B., J.-W. Kwon, T.-O. Kwon, W.-T. Chung, H.-S. Lee, and Y.-C. Kim. 2007. Chemical constituents from the whole plants of Euphorbia supina Rafin. Korean Journal of Pharmacognosy 38: 291–295.

    CAS  Google Scholar 

  • Baker, D.J., T. Wijshake, T. Tchkonia, N.K. Lebrasseur, B.G. Childs, B. Van De Sluis, J.L. Kirkland, and J.M. Van Deursen. 2011. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479: 232–236.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bouktaib, M., A. Atmani, and C. Rolando. 2002. Regio- and stereoselective synthesis of the major metabolite of quercetin, quercetin-3-O-β-d-glucuronide. Tetrahedron Letters 43: 6263–6266.

    Article  CAS  Google Scholar 

  • Campisi, J. 2011. Cellular senescence: Putting the paradoxes in perspective. Current Opinion in Genetics and Development 21: 107–112.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cho, S.C., M.C. Park, B. Keam, J.M. Choi, Y. Cho, S. Hyun, S.C. Park, and J. Lee. 2010. DDS, 4, 4′-diaminodiphenylsulfone, extends organismic lifespan. Proceedings of the National Academy of Sciences of the United States of America 107: 19326–19331.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Collado, M., M.A. Blasco, and M. Serrano. 2007. Cellular senescence in cancer and aging. Cell 130: 223–233.

    Article  CAS  PubMed  Google Scholar 

  • Demidenko, Z.N., S.G. Zubova, E.I. Bukreeva, V.A. Pospelov, T.V. Pospelova, and M.V. Blagosklonny. 2009. Rapamycin decelerates cellular senescence. Cell Cycle 8: 1888–1895.

    Article  CAS  PubMed  Google Scholar 

  • Dimri, G.P., X. Lee, G. Basile, M. Acosta, G. Scott, C. Roskelley, E.E. Medrano, M. Linskens, I. Rubelj, O. Pereira-Smith, and J. Campisi. 1995. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences of the United States of America 92: 9363–9367.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fiorentino, A., B. D’abrosca, S. Pacifico, A. Izzo, M. Letizia, A. Esposito, and P. Monaco. 2008. Potential allelopatic effects of stilbenoids and flavonoids from leaves of Carex distachya Desf. Biochemical Systematics and Ecology 36: 691–698.

    Article  CAS  Google Scholar 

  • Gonzalez Begne, M., N. Yslas, E. Reyes, V. Quiroz, J. Santana, and G. Jimenez. 2001. Clinical effect of a Mexican sanguinaria extract (Polygonum aviculare L.) on gingivitis. Journal of Ethnopharmacology 74: 45–51.

    Article  CAS  PubMed  Google Scholar 

  • Harrison, D.E., R. Strong, Z.D. Sharp, J.F. Nelson, C.M. Astle, K. Flurkey, N.L. Nadon, J.E. Wilkinson, K. Frenkel, C.S. Carter, M. Pahor, M.A. Javors, E. Fernandez, and R.A. Miller. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460: 392–395.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hayflick, L., and P.S. Moorhead. 1961. The serial cultivation of human diploid cell strains. Experimental Cell Research 25: 585–621.

    Article  CAS  PubMed  Google Scholar 

  • Hwang, W.-S., S.-H. Park, H.-S. Kim, H.-J. Kang, M.-J. Kim, S.-J. Oh, J.-B. Park, J. Kim, S.C. Kim, and J.-Y. Lee. 2007. Ascorbic acid extends replicative life span of human embryonic fibroblast by reducing DNA and mitochondrial damages. Nutrition Research and Practice 1: 105–112.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Im, W., J.-Y. Chung, J. Bhan, J. Lim, S.-T. Lee, K. Chu, and M. Kim. 2012. Sun ginseng protects endothelial progenitor cells from senescence associated apoptosis. Journal of Ginseng Research 36: 78–85.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ishizawa, K., Y. Izawa-Ishizawa, S. Ohnishi, Y. Motobayashi, K. Kawazoe, S. Hamano, K. Tsuchiya, S. Tomita, K. Minakuchi, and T. Tamaki. 2009. Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells. Journal of Pharmacological Sciences 109: 257–264.

    Article  CAS  PubMed  Google Scholar 

  • Ishizawa, K., M. Yoshizumi, Y. Kawai, J. Terao, Y. Kihira, Y. Ikeda, S. Tomita, K. Minakuchi, K. Tsuchiya, and T. Tamaki. 2011. Pharmacology in health food: Metabolism of quercetin in vivo and its protective effect against arteriosclerosis. Journal of Pharmacological Sciences 115: 466–470.

    Article  CAS  PubMed  Google Scholar 

  • Jaskelioff, M., F.L. Muller, J.H. Paik, E. Thomas, S. Jiang, A.C. Adams, E. Sahin, M. Kost-Alimova, A. Protopopov, J. Cadinanos, J.W. Horner, E. Maratos-Flier, and R.A. Depinho. 2011. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469: 102–106.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jung, H.A., A.R. Kim, H.Y. Chung, and J.S. Choi. 2002. In vitro antioxidant activity of some selected Prunus species in Korea. Archives of Pharmacal Research 25: 865–872.

    Article  CAS  PubMed  Google Scholar 

  • Kashiwada, Y., G. Nonaka, I. Nishioka, and T. Yamagishi. 1988. Galloyl and hydroxycinnamoylglucoses from Rhubarb. Phytochemistry 27: 1473–1477.

    Article  CAS  Google Scholar 

  • Kim, H.J., K.S. Kim, S.H. Kim, S.H. Baek, H.Y. Kim, C. Lee, and J.R. Kim. 2009a. Induction of cellular senescence by secretory phospholipase A2 in human dermal fibroblasts through an ROS-mediated p53 pathway. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 64: 351–362.

    Article  Google Scholar 

  • Kim, H.J., E.R. Woo, and H.K. Park. 1994. A novel lignin and flavonoids from Polygonum aviculare. Journal of Natural Products 57: 581–586.

    Article  CAS  Google Scholar 

  • Kim, H.Y., B.H. Moon, H.J. Lee, and D.H. Choi. 2004a. Flavonol glycosides from the leaves of Eucommia ulmoides O. with glycation inhibitory activity. Journal of Ethnopharmacology 93: 227–230.

    Article  CAS  PubMed  Google Scholar 

  • Kim, K.S., K.W. Kang, Y.B. Seu, S.H. Baek, and J.R. Kim. 2009b. Interferon-gamma induces cellular senescence through p53-dependent DNA damage signaling in human endothelial cells. Mechanisms of Ageing and Development 130: 179–188.

    Article  CAS  PubMed  Google Scholar 

  • Kim, K.S., Y.B. Seu, S.H. Baek, M.J. Kim, K.J. Kim, J.H. Kim, and J.R. Kim. 2007. Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism. Molecular Biology of the Cell 18: 4543–4552.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim, M.R., S.K. Lee, C.S. Kim, K.S. Kim, and D.C. Moon. 2004b. Phytochemical constituents of Carpesium macrocephalum F(R). et S(AV). Archives of Pharmacal Research 27: 1029–1033.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S.R., J.H. Park, M.E. Lee, J.S. Park, S.C. Park, and J.A. Han. 2008. Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner. Mechanisms of Ageing and Development 129: 706–713.

    Article  CAS  PubMed  Google Scholar 

  • Kuilman, T., C. Michaloglou, W.J. Mooi, and D.S. Peeper. 2010. The essence of senescence. Genes and Development 24: 2463–2479.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kyaw, M., M. Yoshizumi, K. Tsuchiya, Y. Izawa, Y. Kanematsu, and T. Tamaki. 2004. Atheroprotective effects of antioxidants through inhibition of mitogen-activated protein kinases. Acta Pharmacologica Sinica 25: 977–985.

    CAS  PubMed  Google Scholar 

  • Lee, D.-Y., H.-N. Lyu, H.-Y. Kwak, L. Jung, Y.-H. Lee, D.-K. Kim, I.-S. Chung, S.-H. Kim, and N.-I. Baek. 2007. Isolation of flavonoids from the fruits of Cornus kousa Burg. Journal of Applied Biological Chemistry 50: 144–147.

    CAS  Google Scholar 

  • Lu, Y., and L.Y. Foo. 2000. Flavonoid and phenolic glycosides from Salvia officinalis. Phytochemistry 55: 263–267.

    Article  PubMed  Google Scholar 

  • Martin, T., B. Rubio, L. Villaescusa, L. Femandez, and A.M. Diaz. 1999. Polyphenolic compounds from pericarps of Myrtus communis. Pharmaceutical Biology 37: 28–31.

    Article  CAS  Google Scholar 

  • Milan, P.B., D.M. Nejad, A.A. Ghanbari, J.S. Rad, H.T. Nasrabadi, M.H. Roudkenar, A.M. Roushandeh, and M. Goldust. 2011. Effects of Polygonum aviculare herbal extract on sperm parameters after EMF exposure in mouse. Pakistan Journal of Biological Sciences 14: 720–724.

    Article  CAS  PubMed  Google Scholar 

  • Moon, J.H., T. Tsushida, K. Nakahara, and J. Terao. 2001. Identification of quercetin 3-O-beta-d-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radical Biology and Medicine 30: 1274–1285.

    Article  CAS  PubMed  Google Scholar 

  • Nan, J.X., E.J. Park, H.J. Kim, G. Ko, and D.H. Sohn. 2000. Antifibrotic effects of the methanol extract of Polygonum aviculare in fibrotic rats induced by bile duct ligation and scission. Biological and Pharmaceutical Bulletin 23: 240–243.

    Article  CAS  PubMed  Google Scholar 

  • Nees, S., D.R. Weiss, E. Reichenbach-Klinke, F. Rampp, B. Heilmeier, J. Kanbach, and A. Esperester. 2003. Protective effects of flavonoids contained in the red vine leaf on venular endothelium against the attack of activated blood components in vitro. Arzneimittel-Forschung 53: 330–341.

    CAS  PubMed  Google Scholar 

  • Owen, R.W., R. Haubner, W.E. Hull, G. Erben, B. Spiegelhalder, H. Bartsch, and B. Haber. 2003. Isolation and structure elucidation of the major individual polyphenols in carob fibre. Food and Chemical Toxicology 41: 1727–1738.

    Article  CAS  PubMed  Google Scholar 

  • Park, S.Y., J.S. Kim, S.Y. Lee, K. Bae, and S.S. Kang. 2008. Chemical constituents of Lathyrus davidii. Natural Product Sciences 14: 281–282.

    CAS  Google Scholar 

  • Price, K.R., I.J. Colquhoun, K.A. Barnes, and M.J.C. Rhodes. 1998. Composition and content of flavonol glycosides in green beans and their fate during processing. Journal of Agriculture and Food Chemistry 46: 4898–4903.

    Article  CAS  Google Scholar 

  • Rodier, F., and J. Campisi. 2011. Four faces of cellular senescence. Journal of Cell Biology 192: 547–556.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Saijo, R., G.I. Nonaka, and I. Nishioka. 1990. Gallic acid esters of bergenin and norbergenin from Mallotus japonicus. Phytochemistry 29: 267–270.

    Article  CAS  Google Scholar 

  • Schaefer, E., H. Peil, L. Ambrosetti, and O. Petrini. 2003. Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis viniferae) in the treatment of chronic venous insufficiency. A 6-week observational clinical trial. Arzneimittel-Forschung 53: 243–246.

    CAS  PubMed  Google Scholar 

  • Shen, C.-J., C.-K. Chen, and S.-.S. Lee. 2009. Polar constituents from Sageretia thea leaf characterized by HPLC–SPE–NMR assisted approaches. Journal of the Chinese Chemical Society 56: 1002–1009.

    CAS  Google Scholar 

  • Shirai, M., J.H. Moon, T. Tsushida, and J. Terao. 2001. Inhibitory effect of a quercetin metabolite, quercetin 3-O-beta-d-glucuronide, on lipid peroxidation in liposomal membranes. Journal of Agriculture and Food Chemistry 49: 5602–5608.

    Article  CAS  Google Scholar 

  • Shirai, M., R. Yamanishi, J.H. Moon, K. Murota, and J. Terao. 2002. Effect of quercetin and its conjugated metabolite on the hydrogen peroxide-induced intracellular production of reactive oxygen species in mouse fibroblasts. Bioscience, Biotechnology, and Biochemistry 66: 1015–1021.

    Article  CAS  PubMed  Google Scholar 

  • Sohn, S.H., E.Y. Lee, J.H. Lee, Y. Kim, M. Shin, M. Hong, and H. Bae. 2009. Screening of herbal medicines for recovery of acetaminophen-induced nephrotoxicity. Environmental Toxicology and Pharmacology 27: 225–230.

    Article  CAS  PubMed  Google Scholar 

  • Tsuji, M., H. Yamamoto, T. Sato, Y. Mizuha, Y. Kawai, Y. Taketani, S. Kato, J. Terao, T. Inakuma, and E. Takeda. 2009. Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice. Journal of Bone and Mineral Metabolism 27: 673–681.

    Article  CAS  PubMed  Google Scholar 

  • Xie, C., N.C. Veitch, P.J. Houghton, and M.S. Simmonds. 2003. Flavone C-glycosides from Viola yedoensis MAKINO. Chemical and Pharmaceutical Bulletin (Tokyo) 51: 1204–1207.

    Article  CAS  Google Scholar 

  • Yang, H.H., B. Jung, and J.R. Kim. 2010. Identification of plant extracts that inhibit cellular senescence in human fibroblasts, endothelial cells, and vascular smooth muscle cells. Journal of the Korean Society for Applied Biological Chemistry 53: 584–592.

    Article  CAS  Google Scholar 

  • Yang, H.H., J.K. Son, B. Jung, M. Zheng, and J.R. Kim. 2011. Epifriedelanol from the root bark of Ulmus davidiana inhibits cellular senescence in human primary cells. Planta Medica 77: 441–449.

    Article  CAS  PubMed  Google Scholar 

  • Yang, J., Y. Lei, W. Cui, S. Fang, and K. Chen. 2009. Mechanisms of delay endothelial cell replicative senescence by extracts from Panax ginseng, Panax notoginseng and Ligusticum chuanxiong. Zhongguo Zhong Yao Za Zhi 34: 1544–1548.

    PubMed  Google Scholar 

  • Yin, M.H., D.G. Kang, D.H. Choi, T.O. Kwon, and H.S. Lee. 2005. Screening of vasorelaxant activity of some medicinal plants used in oriental medicines. Journal of Ethnopharmacology 99: 113–117.

    Article  PubMed  Google Scholar 

  • Yoon, I.K., H.K. Kim, Y.K. Kim, I.H. Song, W. Kim, S. Kim, S.H. Baek, J.H. Kim, and J.R. Kim. 2004. Exploration of replicative senescence-associated genes in human dermal fibroblasts by cDNA microarray technology. Experimental Gerontology 39: 1369–1378.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, X., P.T. Thuong, W. Jin, N.D. Su, D.E. Sok, K. Bae, and S.S. Kang. 2005. Antioxidant activity of anthraquinones and flavonoids from flower of Reynoutria sachalinensis. Archives of Pharmacal Research 28: 22–27.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (2005-0049417).

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Daegu, 705-717, Republic of Korea

    Hyo Hyun Yang, Jung Hee Cho, Hwa Young Kim, Suk Hwan Baek & Jae-Ryong Kim

  2. Department of Physiology, College of Medicine, Yeungnam University, Daegu, 705-717, Republic of Korea

    So Young Park

  3. Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, 705-717, Republic of Korea

    Hyung Chul Choi

  4. Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, 705-717, Republic of Korea

    Jong-Keun Son, Hwa Young Kim, Suk Hwan Baek, Hyung Chul Choi, So Young Park & Jae-Ryong Kim

  5. College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Republic of Korea

    Kyoung Hwangbo & Jong-Keun Son

  6. College of Pharmacy, Yanbian University, Yanji, 133000, People’s Republic of China

    Ming Shan Zheng

Authors
  1. Hyo Hyun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoung Hwangbo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming Shan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jung Hee Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jong-Keun Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hwa Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Suk Hwan Baek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hyung Chul Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. So Young Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jae-Ryong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jae-Ryong Kim.

Additional information

Hyo Hyun Yang, Kyoung Hwangbo and Ming Shan Zheng contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 108 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, H.H., Hwangbo, K., Zheng, M.S. et al. Quercetin-3-O-β-d-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells. Arch. Pharm. Res. 37, 1219–1233 (2014). https://doi.org/10.1007/s12272-014-0344-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-014-0344-2

Keywords

Search

Navigation