Applied Biochemistry and Biotechnology

, Volume 174, Issue 4, pp 1365–1375 | Cite as

Apigenin and Quercetin Ameliorate Mitochondrial Alterations by Tunicamycin-Induced ER Stress in 3T3-L1 Adipocytes

  • V. M. Nisha
  • S. S. Anusree
  • A. Priyanka
  • K. G. RaghuEmail author


Endoplasmic reticulum (ER) is an important organelle with functions like protein synthesis, folding, and calcium homeostasis. ER stress, a condition that dramatically affects protein folding homeostasis in cells, has been associated with a number of metabolic disorders. Emerging clinical and preclinical evidence support the notion that pharmacological modulators of ER stress have therapeutic potential as a novel target for treating metabolic diseases. ER is in physical contact with mitochondria, and there is a strong cross talk between these organelles at functional level. The present investigation was aimed to check the mitochondrial alterations in adipocytes with tunicamycin-induced ER stress and modulation by apigenin and quercetin. For this, differentiated adipocytes were incubated with tunicamycin (2 μg/ml) for 18 h, and changes in mitochondrial membrane potential, biogenesis, reactive oxygen species production, and adiponectin secretion were seen. Tunicamycin-induced ER stress altered reactive oxygen species (ROS) (6.34-fold↑), membrane potential (4.1-fold↑), mitochondrial biogenesis (2.4-fold↓), and adiponectin secretion (3.5-fold↓). Apigenin and quercetin ameliorated alterations in mitochondria. From results, we conclude that ER stress significantly alters mitochondrial functions and both the bioactives significantly protected mitochondrial alterations during ER stressand reestablished adiponectin secretion.


ER stress Adipocytes Mitochondria ROS Quercetin Apigenin Adiponectin 



We thank Council for Scientific and Industrial Research, Govt. of India, for financial assistance in the form of research fellowship. We are also thankful to the CSIR 12th 5-year plan project “NaPAHA” for financial support. We thank the Director, CSIR-NIIST, and Head, Agroprocessing and Natural Products Division, for providing necessary facilities.

Conflict of Interest

There is no conflict of interest existing between the authors.


  1. 1.
    Trayhurn, P., & Beattie, J. H. (2001). Proceedings of the Nutrition Society, 60, 329–339.CrossRefGoogle Scholar
  2. 2.
    Boden, G., Duan, X., Homko, C., Molina, E. J., Song, W., Perez, O., Cheung, P., & Merali, S. (2008). Diabetes, 57, 2438–2444.CrossRefGoogle Scholar
  3. 3.
    Kawasaki, N., Asada, R., Saito, A., Kanemoto, S., & Imaizumi, K. (2012). Scientific Reports, 2, 799.CrossRefGoogle Scholar
  4. 4.
    Xu, C., Bailly-Maitre, B., & Reed, J. C. (2005). Journal of Clinical Investigation, 115(10), 2656–2664.CrossRefGoogle Scholar
  5. 5.
    Gething, M. J., & Sambrook, J. (1992). Nature, 355, 33–45.CrossRefGoogle Scholar
  6. 6.
    Tsuriya, D., Morita, H., Morioka, T., Takahashi, N., Ito, T., Oki, Y., & Nakamura, H. (2011). Internal Medicine, 50, 2767–2773.CrossRefGoogle Scholar
  7. 7.
    Ellgaard, L., Molinari, M., & Helenius, A. (1999). Science, 286, 1882–1888.CrossRefGoogle Scholar
  8. 8.
    Kaufman, R. J., Scheuner, D., Schroder, M., Shen, X., Lee, K., Liu, C. Y., & Arnold, S. M. (2002). Nature Reviews Molecular Cell Biology, 3, 411–421.CrossRefGoogle Scholar
  9. 9.
    Ron, D. (2002). Journal of Clinical Investigation, 1110, 1383–1388.CrossRefGoogle Scholar
  10. 10.
    Hayashi, T., Rizzuto, R., Hajnoczky, G., & Su, T. P. (2009). Trends in Cell Biology, 2, 81–88.CrossRefGoogle Scholar
  11. 11.
    Simmen, T., Lynes, E. M., Gesson, K., & Thomas, G. (2010). Biochimica et Biophysica Acta, 1798, 1465–1473.CrossRefGoogle Scholar
  12. 12.
    Mondal, A. K., Das, S. K., Varma, V., Nolen, G. T., McGehee, R. E., Elbein, S. C., Wei, J. Y., & Ranganathan, G. (2012). Metabolic Syndrome and Related Disorders, 10, 297–306.CrossRefGoogle Scholar
  13. 13.
    Ozcan, L., Ayse Seda, E., Lu, A., Chung, J., Sarkar, S., Duyu, N., & Myers, M. G. (2009). Cell Metabolism, 9, 35–51.CrossRefGoogle Scholar
  14. 14.
    Yun, J. W. (2010). Possible anti-obesity therapeutics from nature—a review. Phytochemistry, 71, 1625–1641.CrossRefGoogle Scholar
  15. 15.
    Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O'Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N. (2013). Diabetes, 62(4), 1084–1093.CrossRefGoogle Scholar
  16. 16.
    Lee, J. H., Zhou, H. Y., Cho, S. Y., Kim, Y. S., Lee, Y. S., & Jeong, C. S. (2007). Archives of Pharmacal Research, 30(10), 1318–27.CrossRefGoogle Scholar
  17. 17.
    Stewart, L. K., Soileau, J. L., Ribnicky, D., Wang, Z. Q., Raskin, I., Poulev, A., Majewski, M., Cefalu, W. T., & Gettys, T. W. (2008). Metabolism, Clinical and Experimental, 57(7), S39–S46.CrossRefGoogle Scholar
  18. 18.
    Berridge, M. J., Bootman, M. D., & Roderick, H. L. (2003). Nature Reviews Molecular, 4, 517–29.CrossRefGoogle Scholar
  19. 19.
    Deniaud, A., Sharaf el dein, O., Maillier, E., Poncet, D., Kroemer, G., Lemaire, & Brenner, C. (2008). Oncogene, 27, 285–299.CrossRefGoogle Scholar
  20. 20.
    Frizzell, N., Rajesh, M., Jepson, M. J., Nagai, R., Carson, J. A., Thorpe, S. R., & Baynes, J. W. (2009). Journal of Biological Chemistry, 284(38), 25772–81.CrossRefGoogle Scholar
  21. 21.
    Cao, S. S., & Randal, J. K. (2013). Expert Opinion on Therapeutic Targets, 17, 437–448.CrossRefGoogle Scholar
  22. 22.
    Nabin, R., Kim, S. K., Go, H., Joe, Y., Callaway, Z., Kang, J. G., Ryter, S. W., & Chung, H. T. (2013). Oxidative Medicine and Cellular Longevity. doi: 10.1155/2013/154279.
  23. 23.
    Estruch, R., Ros, E., Salas-Salvado, J., Covas, M. I., Corella, D., Aros, F., Gomez-Gracia, E., Ruiz-Gutierrez, V., Fiol, M., & Lapetra, J. (2013). New England Journal of Medicine, 368, 1279–1290.CrossRefGoogle Scholar
  24. 24.
    Nicholas, C., Batra, S., Vargo, M. A., Voss, O. H., Gavrilin, M. A., Wewers, M. D., Guttridge, D. C., Grotewold, E., & Doseff, A. (2007). Journal of Immunology, 179, 7121–7127.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • V. M. Nisha
    • 1
  • S. S. Anusree
    • 1
  • A. Priyanka
    • 1
  • K. G. Raghu
    • 1
    Email author
  1. 1.Agroprocessing and Natural Products DivisionCSIR-National Institute for Interdisciplinary Science and Technology (NIIST)ThiruvananthapuramIndia

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