Advertisement

Inflammation

pp 1–11 | Cite as

Piceatannol Inhibits P. acnes–Induced Keratinocyte Proliferation and Migration by Downregulating Oxidative Stress and the Inflammatory Response

  • Tingting Zhu
  • Fumin Fang
  • Dongjie Sun
  • Shuyun Yang
  • Xiaoping Zhang
  • Xiuqin YuEmail author
  • Li YangEmail author
Original Article
  • 44 Downloads

Abstract

The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3′, 4′-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.

KEY WORDS

acne vulgaris Propionibacterium acnes Piceatannol nuclear factor erythroid 2-related factor 2 anti-inflammation 

Notes

Funding Information

This study was partly supported by the National Science Foundation of China (no. 81560506, U1402223, 81460469 and 81760559).

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflict of interest.

References

  1. 1.
    Agamia, N.F., D.M. Abdallah, O. Sorour, B. Mourad, and D.N. Younan. 2016. Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet. The British Journal of Dermatology 174 (6): 1299–1307.  https://doi.org/10.1111/bjd.14409.CrossRefPubMedGoogle Scholar
  2. 2.
    Ahn, J., Y.W. Chung, J.B. Park, and K.M. Yang. 2018. omega-hydroxyundec-9-enoic acid induces apoptosis by ROS mediated JNK and p38 phosphorylation in breast cancer cell lines. Journal of Cellular Biochemistry 119 (1): 998–1007.  https://doi.org/10.1002/jcb.26267.CrossRefPubMedGoogle Scholar
  3. 3.
    Akinwumi, B.C., K.M. Bordun, and H.D. Anderson. 2018. Biological activities of stilbenoids. International Journal of Molecular Sciences 19 (3).  https://doi.org/10.3390/ijms19030792.CrossRefGoogle Scholar
  4. 4.
    Alam, J., D. Stewart, C. Touchard, S. Boinapally, A.M. Choi, and J.L. Cook. 1999. Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. The Journal of Biological Chemistry 274 (37): 26071–26078.  https://doi.org/10.1074/jbc.274.37.26071.CrossRefPubMedGoogle Scholar
  5. 5.
    Ashikawa, K., S. Majumdar, S. Banerjee, A.C. Bharti, S. Shishodia, and B.B. Aggarwal. 2002. Piceatannol inhibits TNF-induced NF-kappaB activation and NF-kappaB-mediated gene expression through suppression of IkappaBalpha kinase and p65 phosphorylation. Journal of Immunology 169 (11): 6490–6497.  https://doi.org/10.4049/jimmunol.169.11.6490.CrossRefGoogle Scholar
  6. 6.
    Bridgeman, B.B., P. Wang, B.P. Ye, J.C. Pelling, O.V. Volpert, and X. Tong. 2016. Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: a new implication of skin cancer prevention. Cellular Signalling 28 (5): 460–468.  https://doi.org/10.1016/j.cellsig.2016.02.008.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Carr, T.D., J. DiGiovanni, C.J. Lynch, and L.M. Shantz. 2012. Inhibition of mTOR Suppresses UVB-Induced Keratinocyte Proliferation and Survival. Cancer Prevention Research 5 (12): 1394–1404.  https://doi.org/10.1158/1940-6207.Capr-12-0272-T.CrossRefPubMedGoogle Scholar
  8. 8.
    Chartoumpekis, D.V., N. Wakabayashi, and T.W. Kensler. 2015. Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism. Biochemical Society Transactions 43 (4): 639–644.  https://doi.org/10.1042/BST20150049.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Choi, K.H., J.E. Kim, N.R. Song, J.E. Son, M.K. Hwang, S. Byun, J.H. Kim, K.W. Lee, and H.J. Lee. 2010. Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells. Cardiovascular Research 85 (4): 836–844.  https://doi.org/10.1093/cvr/cvp359.CrossRefPubMedGoogle Scholar
  10. 10.
    Cong, T.X., D. Hao, X. Wen, X.H. Li, G. He, and X. Jiang. 2019. From pathogenesis of acne vulgaris to anti-acne agents. Archives of Dermatological Research 311 (5): 337–349.  https://doi.org/10.1007/s00403-019-01908-x.CrossRefPubMedGoogle Scholar
  11. 11.
    Cordova-Gomez, M., A. Galano, and J.R. Alvarez-Idaboy. 2013. Piceatannol, a better peroxyl radical scavenger than resveratrol. RSC Advances 3 (43): 20209–20218.  https://doi.org/10.1039/c3ra42923g.CrossRefGoogle Scholar
  12. 12.
    Das, S., and R.V. Reynolds. 2014. Recent advances in acne pathogenesis: implications for therapy. American Journal of Clinical Dermatology 15 (6): 479–488.  https://doi.org/10.1007/s40257-014-0099-z.CrossRefPubMedGoogle Scholar
  13. 13.
    Frombaum, M., P. Therond, R. Djelidi, J.L. Beaudeux, D. Bonnefont-Rousselot, and D. Borderie. 2011. Piceatannol is more effective than resveratrol in restoring endothelial cell dimethylarginine dimethylaminohydrolase expression and activity after high-glucose oxidative stress. Free Radical Research 45 (3): 293–302.  https://doi.org/10.3109/10715762.2010.527337.CrossRefPubMedGoogle Scholar
  14. 14.
    Fu, Y., Y. Wang, L. Du, C. Xu, J. Cao, T. Fan, J. Liu, et al. 2013. Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation. International Journal of Molecular Sciences 14 (7): 14105–14118.  https://doi.org/10.3390/ijms140714105.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Grange, P.A., C. Chereau, J. Raingeaud, C. Nicco, B. Weill, N. Dupin, and F. Batteux. 2009. Production of superoxide anions by keratinocytes initiates P. acnes-induced inflammation of the skin. PLoS Pathogens 5 (7): e1000527.  https://doi.org/10.1371/journal.ppat.1000527.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    He, Q., Z. Li, Y. Wang, Y. Hou, L. Li, and J. Zhao. 2017. Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction. International Immunopharmacology 50: 208–215.  https://doi.org/10.1016/j.intimp.2017.06.029.CrossRefPubMedGoogle Scholar
  17. 17.
    Hsieh, T.C., C.Y. Lin, H.Y. Lin, and J.M. Wu. 2012. AKT/mTOR as novel targets of polyphenol piceatannol possibly contributing to inhibition of proliferation of cultured prostate cancer cells. ISRN Urology 2012: 272697.  https://doi.org/10.5402/2012/272697.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hur, K.Y., S.H. Kim, M.A. Choi, D.R. Williams, Y.H. Lee, S.W. Kang, U.C. Yadav, S.K. Srivastava, M. Jung, J.W. Cho, S.G. Kim, E.S. Kang, E.J. Lee, and H.C. Lee. 2010. Protective effects of magnesium lithospermate B against diabetic atherosclerosis via Nrf2-ARE-NQO1 transcriptional pathway. Atherosclerosis 211 (1): 69–76.  https://doi.org/10.1016/j.atherosclerosis.2010.01.035.CrossRefPubMedGoogle Scholar
  19. 19.
    Jahns, A.C., B. Lundskog, R. Ganceviciene, R.H. Palmer, I. Golovleva, C.C. Zouboulis, A. McDowell, S. Patrick, and O.A. Alexeyev. 2012. An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study. The British Journal of Dermatology 167 (1): 50–58.  https://doi.org/10.1111/j.1365-2133.2012.10897.x.CrossRefPubMedGoogle Scholar
  20. 20.
    Jahns, A.C., H. Eilers, R. Ganceviciene, and O.A. Alexeyev. 2015. Propionibacterium species and follicular keratinocyte activation in acneic and normal skin. The British Journal of Dermatology 172 (4): 981–987.  https://doi.org/10.1111/bjd.13436.CrossRefPubMedGoogle Scholar
  21. 21.
    Jiang, L., L. Zhang, K. Kang, D. Fei, R. Gong, Y. Cao, S. Pan, M. Zhao, and M. Zhao. 2016. Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation. Biomedicine & Pharmacotherapy 84: 130–138.  https://doi.org/10.1016/j.biopha.2016.09.020.CrossRefGoogle Scholar
  22. 22.
    Kistowska, M., S. Gehrke, D. Jankovic, K. Kerl, A. Fettelschoss, L. Feldmeyer, G. Fenini, A. Kolios, A. Navarini, R. Ganceviciene, J. Schauber, E. Contassot, and L.E. French. 2014. IL-1beta drives inflammatory responses to propionibacterium acnes in vitro and in vivo. The Journal of Investigative Dermatology 134 (3): 677–685.  https://doi.org/10.1038/jid.2013.438.CrossRefPubMedGoogle Scholar
  23. 23.
    Kita, Y., Y. Miura, and K. Yagasaki. 2012. Antiproliferative and anti-invasive effect of piceatannol, a polyphenol present in grapes and wine, against hepatoma AH109A cells. Journal of Biomedicine and Biotechnology.  https://doi.org/10.1155/2012/672416.CrossRefGoogle Scholar
  24. 24.
    Ko, Y.J., H.H. Kim, E.J. Kim, Y. Katakura, W.S. Lee, G.S. Kim, and C.H. Ryu. 2013. Piceatannol inhibits mast cell-mediated allergic inflammation. International Journal of Molecular Medicine 31 (4): 951–958.  https://doi.org/10.3892/ijmm.2013.1283.CrossRefPubMedGoogle Scholar
  25. 25.
    Kobayashi, M., and M. Yamamoto. 2005. Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxidants & Redox Signaling 7 (3-4): 385–394.  https://doi.org/10.1089/ars.2005.7.385.CrossRefGoogle Scholar
  26. 26.
    Liu, D., D.H. Kim, J.M. Park, H.K. Na, and Y.J. Surh. 2009. Piceatannol inhibits phorbol ester-induced NF-kappa B activation and COX-2 expression in cultured human mammary epithelial cells. Nutrition and Cancer 61 (6): 855–863.  https://doi.org/10.1080/01635580903285080.CrossRefPubMedGoogle Scholar
  27. 27.
    Maruki-Uchida, H., I. Kurita, K. Sugiyama, M. Sai, K. Maeda, and T. Ito. 2013. The protective effects of piceatannol from passion fruit (Passiflora edulis) seeds in UVB-irradiated keratinocytes. Biological & Pharmaceutical Bulletin 36 (5): 845–849.  https://doi.org/10.1248/bpb.b12-00708.CrossRefGoogle Scholar
  28. 28.
    Melnik, B.C. 2018. Acne vulgaris: the metabolic syndrome of the pilosebaceous follicle. Clinics in Dermatology 36 (1): 29–40.  https://doi.org/10.1016/j.clindermato1.2017.09.006.CrossRefPubMedGoogle Scholar
  29. 29.
    Melnik, B.C. 2018. Overexpression of p53 explains isotretinoin's teratogenicity. Experimental Dermatology 27 (1): 91–93.  https://doi.org/10.1111/exd.13420.CrossRefPubMedGoogle Scholar
  30. 30.
    Melnik, B.C., and C.C. Zouboulis. 2013. Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne. Experimental Dermatology 22 (5): 311–315.  https://doi.org/10.1111/exd.12142.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Mirnezami, M., and H. Rahimi. 2018. Is Oral Omega-3 Effective in Reducing Mucocutaneous Side Effects of Isotretinoin in Patients with Acne Vulgaris? Dermatology Research and Practice 2018: 6974045.  https://doi.org/10.1155/2018/6974045.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Puhvel, S.M., M. Barfatani, M. Warnick, and T.H. Sternberg. 1964. Study of antibody levels to corynebacterium acnes. in the serum of patients with acne vulgaris, using bacterial agglutination, agar gel immunodiffusion, and immunofluorescence techniques. Archives of Dermatology 90: 421–427.  https://doi.org/10.1001/archderm.1964.01600040049011.CrossRefPubMedGoogle Scholar
  33. 33.
    Son, Y., S.J. Byun, and H.O. Pae. 2013. Involvement of heme oxygenase-1 expression in neuroprotection by piceatannol, a natural analog and a metabolite of resveratrol, against glutamate-mediated oxidative injury in HT22 neuronal cells. Amino Acids 45 (2): 393–401.  https://doi.org/10.1007/s00726-013-1518-9.CrossRefPubMedGoogle Scholar
  34. 34.
    Song, H., J.I. Jung, H.J. Cho, S. Her, S.H. Kwon, R. Yu, Y.H. Kang, K.W. Lee, and J.H.Y. Park. 2015. Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration. Journal of Nutritional Biochemistry 26 (11): 1368–1378.  https://doi.org/10.1016/j.jnutbio.2015.07.005.CrossRefPubMedGoogle Scholar
  35. 35.
    Suh, D.H., and H.H. Kwon. 2015. What's new in the physiopathology of acne? The British Journal of Dermatology 172 (Suppl 1): 13–19.  https://doi.org/10.1111/bjd.13634.CrossRefPubMedGoogle Scholar
  36. 36.
    Sun, X., X. Shen, R. Jain, Y. Lin, J. Wang, J. Sun, J. Wang, Y. Yan, and Q. Yuan. 2015. Synthesis of chemicals by metabolic engineering of microbes. Chemical Society Reviews 44 (11): 3760–3785.  https://doi.org/10.1039/c5cs00159e.CrossRefPubMedGoogle Scholar
  37. 37.
    Tang, Q., Z. Feng, M. Tong, J. Xu, G. Zheng, L. Shen, P. Shang, Y. Zhang, and H. Liu. 2017. Piceatannol inhibits the IL-1beta-induced inflammatory response in human osteoarthritic chondrocytes and ameliorates osteoarthritis in mice by activating Nrf2. Food & Function 8 (11): 3926–3937.  https://doi.org/10.1039/c7fo00822h.CrossRefGoogle Scholar
  38. 38.
    Vo, D.D., and M. Elofsson. 2016. Total synthesis of viniferifuran, resveratrol-piceatannol hybrid, anigopreissin A and analogues - investigation of demethylation strategies. Advanced Synthesis & Catalysis 358 (24): 4085–4092.  https://doi.org/10.1002/adsc.201601089.CrossRefGoogle Scholar
  39. 39.
    Wang, Y.Y., A.R. Ryu, S. Jin, Y.M. Jeon, and M.Y. Lee. 2017. Chlorin e6-mediated photodynamic therapy suppresses P. acnes-induced inflammatory response via NFkappaB and MAPKs signaling pathway. PLoS One 12 (1): e0170599.  https://doi.org/10.1371/journal.pone.0170599.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Youn, J., J.S. Lee, H.K. Na, J.K. Kundu, and Y.J. Surh. 2009. Resveratrol and piceatannol inhibit iNOS expression and NF-kappa B activation in dextran sulfate sodium-induced mouse colitis. Nutrition and Cancer-an International Journal 61 (6): 847–854.  https://doi.org/10.1080/01635580903285072.CrossRefGoogle Scholar
  41. 41.
    Zhai, J., J. Shen, G. Xie, J. Wu, M. He, L. Gao, Y. Zhang, X. Yao, and L. Shen. 2019. Cancer-associated fibroblasts-derived IL-8 mediates resistance to cisplatin in human gastric cancer. Cancer Letters 454: 37–43.  https://doi.org/10.1016/j.canlet.2019.04.002.CrossRefPubMedGoogle Scholar
  42. 42.
    Zouboulis, C. 2019. Neuroendocrinology of Acne Vulgaris. Acta Dermato-Venereologica 99 (8): 739–739.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of DermatologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of DermatologyFirst Affiliated Hospital of Kunming Medical UniversityKunmingChina
  3. 3.Department of DermatologyThe People’s Hospital of BaoshanBaoshan CityChina
  4. 4.Department of Dermatology, Henan Provincial People’s HospitalThe People’s Hospital of Zhengzhou UniversityZhengzhouChina

Personalised recommendations