Skip to main content

Advertisement

SpringerLink
Log in

Extract of Litsea japonica ameliorates blood–retinal barrier breakdown in db/db mice

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Loss of blood–retinal barrier (BRB) properties is an important feature in the pathology of diabetic retinopathy. Endothelium integrity is important for the normal vascular function. Litsea japonica (Thunb.) Jussieu is a Korean native plant that is consumed as a vegetable food. In this study, we evaluated the ability of an ethanol extract of L. japonica to prevent retinal vascular leakages in db/db mice, which is an animal model of type II diabetes. L. japonica extracts (LJE, 100 and 250 mg/kg) were administered once a day, orally, for 12 weeks. Vehicle-treated db/db mice exhibited hyperglycemia and retinal vascular leakage. LJE treatment blocked diabetes-induced BRB breakdown and decreased retinal VEGF expression in db/db mice. LJE also inhibited the degradation of occludin, which is an important tight junction protein. These findings support the potential therapeutic usefulness of L. japonica for retinal vascular permeability 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

Similar content being viewed by others

References

  1. J. Cunha-Vaz, R. Bernardes, Nonproliferative retinopathy in diabetes type 2. Initial stages and characterization of phenotypes. Prog. Retin. Eye Res. 24, 355–377 (2005)

    Article  PubMed  Google Scholar 

  2. S. Roy, T. Sato, G. Paryani, R. Kao, Downregulation of fibronectin overexpression reduces basement membrane thickening and vascular lesions in retinas of galactose-fed rats. Diabetes 52, 1229–1234 (2003)

    Article  CAS  PubMed  Google Scholar 

  3. J.P. De La Cruz, J.A. Gonzalez-Correa, A. Guerrero, F.S. de la Cuesta, Pharmacological approach to diabetic retinopathy. Diabetes Metab. Res. Rev. 20, 91–113 (2004)

    Article  Google Scholar 

  4. S.E. Moss, R. Klein, B.E. Klein, The 14-year incidence of visual loss in a diabetic population. Ophthalmology 105, 998–1003 (1998)

    Article  CAS  PubMed  Google Scholar 

  5. R. Klein, B.E. Klein, S.E. Moss, M.D. Davis, D.L. DeMets, The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology 91, 1464–1474 (1984)

    Article  CAS  PubMed  Google Scholar 

  6. C. Kaur, W.S. Foulds, E.A. Ling, Blood–retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management. Prog. Retin. Eye Res. 27, 622–647 (2008)

    Article  CAS  PubMed  Google Scholar 

  7. D. Mehta, A.B. Malik, Signaling mechanisms regulating endothelial permeability. Physiol. Rev. 86, 279–367 (2006)

    Article  CAS  PubMed  Google Scholar 

  8. N.S. Harhaj, D.A. Antonetti, Regulation of tight junctions and loss of barrier function in pathophysiology. Int. J. Biochem. Cell Biol. 36, 1206–1237 (2004)

    Article  CAS  PubMed  Google Scholar 

  9. A.J. Barber, A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 283–290 (2003)

    Article  CAS  PubMed  Google Scholar 

  10. F.J. Alarcon-Aguilara, R. Roman-Ramos, S. Perez-Gutierrez, A. Aguilar-Contreras, C.C. Contreras-Weber, J.L. Flores-Saenz, Study of the anti-hyperglycemic effect of plants used as antidiabetics. J. Ethnopharmacol. 61, 101–110 (1998)

    Article  CAS  PubMed  Google Scholar 

  11. W.L. Li, H.C. Zheng, J. Bukuru, N. De Kimpe, Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J. Ethnopharmacol. 92, 1–21 (2004)

    Article  CAS  PubMed  Google Scholar 

  12. S.Y. Lee, B.S. Min, J.H. Kim, J. Lee, T.J. Kim, C.S. Kim, Y.H. Kim, H.K. Lee, Flavonoids from the leaves of Litsea japonica and their anti-complement activity. Phytother. Res. 19, 273–276 (2005)

    Article  CAS  PubMed  Google Scholar 

  13. B.S. Min, S.Y. Lee, J.H. Kim, O.K. Kwon, B.Y. Park, R.B. An, J.K. Lee, H.I. Moon, T.J. Kim, Y.H. Kim, H. Joung, H.K. Lee, Lactones from the leaves of Litsea japonica and their anti-complement activity. J. Nat. Prod. 66, 1388–1390 (2003)

    Article  CAS  PubMed  Google Scholar 

  14. S.J. Wang, Y. Tong, S. Lu, R. Yang, X. Liao, Y.F. Xu, X. Li, Anti-inflammatory activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves. Planta Med. 76, 1492–1496 (2010)

    Article  CAS  PubMed  Google Scholar 

  15. D. Mantle, F. Eddeb, A.T. Pickering, Comparison of relative antioxidant activities of British medicinal plant species in vitro. J. Ethnopharmacol. 72, 47–51 (2000)

    Article  CAS  PubMed  Google Scholar 

  16. D.G. Kang, C. Yun, H.S. Lee, Screening and comparison of antioxidant activity of solvent extracts of herbal medicines used in Korea. J. Ethnopharmacol. 87, 231–236 (2003)

    Article  PubMed  Google Scholar 

  17. A.N. Witmer, G.F. Vrensen, C.J. Van Noorden, R.O. Schlingemann, Vascular endothelial growth factors and angiogenesis in eye disease. Prog. Retin. Eye. Res. 22, 1–29 (2003)

    Article  CAS  PubMed  Google Scholar 

  18. T. Murata, T. Ishibashi, A. Khalil, Y. Hata, H. Yoshikawa, H. Inomata, Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmic Res. 27, 48–52 (1995)

    Article  CAS  PubMed  Google Scholar 

  19. S.A. Vinores, A.I. Youssri, J.D. Luna, Y.S. Chen, S. Bhargave, M.A. Vinores, C.L. Schoenfeld, B. Peng, C.C. Chan, W. LaRochelle, W.R. Green, P.A. Campochiaro, Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease. Histol. Histopathol. 12, 99–109 (1997)

    CAS  PubMed  Google Scholar 

  20. I. Suzuma, Y. Hata, A. Clermont, F. Pokras, S.L. Rook, K. Suzuma, E.P. Feener, L.P. Aiello, Cyclic stretch and hypertension induce retinal expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2: potential mechanisms for exacerbation of diabetic retinopathy by hypertension. Diabetes 50, 444–454 (2001)

    Article  CAS  PubMed  Google Scholar 

  21. E.C. Tsilibary, Microvascular basement membranes in diabetes mellitus. J. Pathol. 200, 537–546 (2003)

    Article  CAS  PubMed  Google Scholar 

  22. T.N. Crawford, D.V. Alfaro 3rd, J.B. Kerrison, E.P. Jablon, Diabetic retinopathy and angiogenesis. Curr. Diabetes Rev. 5, 8–13 (2009)

    Article  CAS  PubMed  Google Scholar 

  23. D.Y. Yu, S.J. Cringle, E.N. Su, P.K. Yu, G. Jerums, M.E. Cooper, Pathogenesis and intervention strategies in diabetic retinopathy. Clin. Experiment. Ophthalmol. 29, 164–166 (2001)

    Article  CAS  PubMed  Google Scholar 

  24. D.A. Antonetti, A.J. Barber, S. Khin, E. Lieth, J.M. Tarbell, T.W. Gardner, Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 47, 1953–1959 (1998)

    Article  CAS  PubMed  Google Scholar 

  25. M. Furuse, T. Hirase, M. Itoh, A. Nagafuchi, S. Yonemura, S. Tsukita, Occludin: a novel integral membrane protein localizing at tight junctions. J. Cell Biol. 123, 1777–1788 (1993)

    Article  CAS  PubMed  Google Scholar 

  26. P.M. Watson, J.M. Anderson, C.M. Vanltallie, S.R. Doctrow, The tight-junction-specific protein ZO-1 is a component of the human and rat blood–brain barriers. Neurosci. Lett. 129, 6–10 (1991)

    Article  CAS  PubMed  Google Scholar 

  27. T. Hirase, J.M. Staddon, M. Saitou, Y. Ando-Akatsuka, M. Itoh, M. Furuse, K. Fujimoto, S. Tsukita, L.L. Rubin, Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci. 110, 1603–1613 (1997)

    CAS  PubMed  Google Scholar 

  28. C. Campa, S.P. Harding, Anti-VEGF compounds in the treatment of neovascular age related macular degeneration. Curr. Drug Targets 12, 173–181 (2011)

    Article  CAS  PubMed  Google Scholar 

  29. E. Chen, J. Hsu, C.H. Park, Acute visual acuity loss following intravitreal bevacizumab for diabetic macular edema. Ophthalmic. Surg. Lasers Imaging 40, 68–70 (2009)

    Article  PubMed  Google Scholar 

  30. S.C. Costa, P.A. Girard, M. Brehelin, R. Zumbihl, The emerging human pathogen Photorhabdus asymbiotica is a facultative intracellular bacterium and induces apoptosis of macrophage-like cells. Infect. Immun. 77, 1022–1030 (2009)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. M. Bimakr, R.L.A. Rahman, F.S. Taip, A. Ganjloo, L.M. Salleh, J. Selamat, A. Hamid, I.S.M. Zaidul, Comparison of different extraction methods for the extraction of major bioactive flavonoid compounds from spearmint (Mentha spicata L.) leaves. Food Bioprod. Process. 89, 67–72 (2011)

    Article  Google Scholar 

  32. L. Fan, Y. Zhang, R. Huang, S. Qin, T. Yi, F. Xu, Y. Tang, X. Qu, H. Chen, J. Miao, Determination of five flavonoids in different parts of Fordia cauliflora by ultra performance liquid chromatography/triple–quadrupole mass spectrometry and chemical comparison with the root of Millettia pulchra var. laxior. Chem. Cent. J. 7, 126 (2013)

    Article  PubMed Central  PubMed  Google Scholar 

  33. T. Suzuki, H. Hara, Role of flavonoids in intestinal tight junction regulation. J. Nutr. Biochem. 22, 401–408 (2011)

    Article  CAS  PubMed  Google Scholar 

  34. A.M. Robert, J.M. Tixier, L. Robert, J.M. Legeais, G. Renard, Effect of procyanidolic oligomers on the permeability of the blood–brain barrier. Pathol. Biol. 49, 298–304 (2001)

    Article  CAS  PubMed  Google Scholar 

  35. K. Taguchi, Y. Hagiwara, K. Kajiyama, Y. Suzuki, Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin. Yakugaku Zasshi 113, 327–333 (1993)

    CAS  PubMed  Google Scholar 

  36. T. Yokozawa, E. Dong, Y. Kawai, M. Gemba, M. Shimizu, Protective effects of some flavonoids on the renal cellular membrane. Exp. Toxicol. Pathol. 51, 9–14 (1999)

    Article  CAS  PubMed  Google Scholar 

  37. S. Noda, S. Tanabe, T. Suzuki, Differential effects of flavonoids on barrier integrity in human intestinal Caco-2 cells. J. Agric. Food Chem. 60, 4628–4633 (2012)

    Article  CAS  PubMed  Google Scholar 

  38. V. Poulaki, W. Qin, A.M. Joussen, P. Hurlbut, S.J. Wiegand, J. Rudge, G.D. Yancopoulos, A.P. Adamis, Acute intensive insulin therapy exacerbates diabetic blood–retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. J. Clin. Invest. 109, 805–815 (2002)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by a Grant [K12040] from the Korea Institute of Oriental Medicine (KIOM).

Conflict of interest

The Authors declare that they have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 305-811, South Korea

    Junghyun Kim, Chan-Sik Kim, Ik Soo Lee, Yun Mi Lee, Eunjin Sohn, Kyuhyung Jo & Jin Sook Kim

  2. Department of Life Science, Gacheon University, Seongnam, Kyonggi-do, 461-701, Republic of Korea

    Joo Hwan Kim

Authors
  1. Junghyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chan-Sik Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ik Soo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun Mi Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eunjin Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyuhyung Jo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joo Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jin Sook Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin Sook Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, J., Kim, CS., Lee, I.S. et al. Extract of Litsea japonica ameliorates blood–retinal barrier breakdown in db/db mice. Endocrine 46, 462–469 (2014). https://doi.org/10.1007/s12020-013-0085-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-013-0085-x

Keywords

Search

Navigation