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Anthocyanins from black soybean seed coat prevent radiation-induced skin fibrosis by downregulating TGF-β and Smad3 expression

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Abstract

The aim of this study was to evaluate the protective effects of anthocyanins from the black soybean seed coat against radiation injury in dermal fibroblasts and mouse skin. Dermal fibroblasts treated with 50 and 100 µg/mL anthocyanins were irradiated with single doses of 20 Gy. Cell viability, intracellular reactive oxygen species (ROS) production, and mRNA expression were measured. A total of 60 mice were used for an in vivo study. A dose of 100 µg/mL anthocyanins was administered daily for 5 days before or after radiation therapy. Following irradiation (45 Gy), mice were inspected for gross pathology twice per wk for 8 weeks. At 4 and 8 weeks post-irradiation, dorsal skin was harvested for histopathologic examination and protein isolation. In dermal fibroblasts, treatment with 50 and 100 µg/mL anthocyanins significantly reduced radiation-induced apoptosis at 72 h and intracellular reactive oxygen species generation at 48 h. Furthermore, 100 µg/mL anthocyanins markedly decreased Smad3 mRNA expression and increased Smad7 mRNA expression at 72 h post-irradiation. In mice, treatment with 100 µg/mL anthocyanins resulted in a significant reduction in the level of skin injury, epidermal thickness, and collagen deposition after irradiation. Treatment with 100 µg/mL anthocyanins significantly decreased the number of α-SMA-, TGF-β-, and Smad3-positive cells after irradiation. Our study demonstrated that black soybean anthocyanins inhibited radiation-induced fibrosis by downregulating TGF-β and Smad3 expression. Therefore, anthocyanins may be a safe and effective candidate for the prevention of radiation-induced skin fibrosis.

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References

  1. Bentzen SM (2006) Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer 6:702–713

    Article  PubMed  CAS  Google Scholar 

  2. Di Franco R, Calvanese M, Murino P, Manzo R et al (2012) Skin toxicity from external beam radiation therapy in breast cancer patients: protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor®). Radiat Oncol 7:12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Grotendorst GR, Okochi H, Hayashi N (1996) A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ 7:469–480

    PubMed  CAS  Google Scholar 

  4. Ha US, Bae WJ, Kim SJ, Yoon BI et al (2015) Anthocyanin induces apoptosis of DU-145 cells in vitro and inhibits xenograft growth of prostate cancer. Yonsei Med J 56:16–23

    Article  PubMed  CAS  Google Scholar 

  5. Hopewell JW (1990) The skin: its structure and response to ionizing radiation. Int J Radiat Biol 57:751–773

    Article  PubMed  CAS  Google Scholar 

  6. Janko M, Ontiveros F, Fitzgerald TJ, Deng A, DeCicco M, Rock KL (2012) IL-1 generated subsequent to radiation-induced tissue injury contributes to the pathogenesis of radiodermatitis. Radiat Res 178:166–172

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Kim HJ, Tsoy I, Park JM, Chung JI, Shin SC, Chang KC (2006) Anthocyanins from soybean seed coat inhibit the expression of TNF-alpha-induced genes associated with ischemia/reperfusion in endothelial cell by NF-kappaB-dependent pathway and reduce rat myocardial damages incurred by ischemia and reperfusion in vivo. FEBS Lett 580:1391–1397

    Article  PubMed  CAS  Google Scholar 

  8. Kim HJ, Xu L, Chang KC, Shin SC et al (2012) Anti-inflammatory effects of anthocyanins from black soybean seed coat on the keratinocytes and ischemia-reperfusion injury in rat skin flaps. Microsurgery 32:563–570

    Article  PubMed  Google Scholar 

  9. Kim SM, Chung MJ, Ha TJ, Choi HN et al (2012) Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids. Life Sci 90:874–882

    Article  PubMed  CAS  Google Scholar 

  10. Leask A, Holmes A, Black CM, Abraham DJ (2003) Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem 278:13008–13015

    Article  PubMed  CAS  Google Scholar 

  11. Lim MJ, Ahn J, Yi JY, Kim MH et al (2014) Induction of galectin-1 by TGF-β1 accelerates fibrosis through enhancing nuclear retention of Smad2. Exp Cell Res 326:125–135

    Article  PubMed  CAS  Google Scholar 

  12. Martin M, Lefaix J, Delanian S (2000) TGF- β1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys 47:277–290

    Article  PubMed  CAS  Google Scholar 

  13. Miko Enomoto T, Johnson T, Peterson N, Homer L, Walts D, Johnson N et al (2005) Combination glutathione and anthocyanins as an alternative for skin care during external-beam radiation. Am J Surg 189:627–630

    Article  PubMed  CAS  Google Scholar 

  14. Nizamutdinova IT, Kim YM, Chung JI, Shin SC et al (2009) Anthocyanins from black soybean seed coats stimulate wound healing in fibroblasts and keratinocytes and prevent inflammation in endothelial cells. Food Chem Toxicol 47:2806–2812

    Article  PubMed  CAS  Google Scholar 

  15. Okunieff P, Xu J, Hu D, Liu W et al (2006) Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines. Int J Radiat Oncol Biol Phys 65:890–898

    Article  PubMed  CAS  Google Scholar 

  16. Ozkol HU, Koyuncu I, uluce Y, Dilsiz N, Soral S, Ozkol H (2015) Anthocyanin-rich extract from Hibiscus sabdariffa calyx counteracts UVC-caused impairments in rats. Pharm Biol 53:1435–1441

    Article  PubMed  CAS  Google Scholar 

  17. Paik SS, Jeong E, Jung SW, Ha TJ et al (2012) Anthocyanins from the seed coat of black soybean reduce retinal degeneration induced by N-methyl-N-nitrosourea. Exp Eye Res 97:55–62

    Article  PubMed  CAS  Google Scholar 

  18. Park MY, Kim JM, Kim JS, Choung MG, Sung MK (2015) Chemopreventive action of anthocyanin-rich black soybean fraction in APC (Min/+) intestinal polyposis model. J Cancer Prev 20:193–201

    Article  PubMed  PubMed Central  Google Scholar 

  19. Roberts AB, Sporn MB (1993) A major advance in the use of growth factors to enhance wound healing. J Clin Invest 92:2565–2566

    Article  PubMed  PubMed Central  Google Scholar 

  20. Shin YS, Shin HA, Kang SU, Kim JH, Oh YT, Park KH, Kim CH (2013) Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study. PLoS One 8:e69151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Sohn DW, Bae WJ, Kim HS, Kim SW, Kim SW (2014) The anti-inflammatory and antifibrosis effects of anthocyanin extracted from black soybean on a Peyronie disease rat model. Urology 84:1112–1116

    Article  PubMed  Google Scholar 

  22. Sultan SM, Stern CS, Allen RJ Jr, Thanik VD, Chang CC et al (2011) Human fat grafting alleviates radiation skin damage in a murine model. Plast Reconstr Surg 128:363–372

    Article  PubMed  CAS  Google Scholar 

  23. Thanik VD, Chang CC, Zoumalan RA, Lerman OZ et al (2011) A novel mouse model of cutaneous radiation injury. Plast Reconstr Surg 127:560–568

    Article  PubMed  CAS  Google Scholar 

  24. Xu L, Choi TH, Kim S, Kim SH et al (2013) Anthocyanins from black soybean seed coat enhance wound healing. Ann Plast Surg 71:415–420

    Article  PubMed  CAS  Google Scholar 

  25. Yan S, Brown SL, Kolozsvary A, Freytag SO, Lu M, Kim JH (2008) Mitigation of radiation-induced skin injury by AAV2-mediated MnSOD gene therapy. J Gene Med 10:1012–1018

    Article  PubMed  CAS  Google Scholar 

  26. Zhang HY, Phan SH (1999) Inhibition of myofibroblast apoptosis by transforming growth factor beta(1). Am J Respir Cell Mol Biol 21:658–665

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF-2014R1A1A1006634) and NRF grant funded by the Korea Government (MSIP) (No. 2014R1A5A2010008).

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Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea

    Sang Woo Park

  2. Department of Plastic and Reconstructive Surgery, Keimyung University School of Medicine, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea

    Jaehoon Choi, Junhyung Kim & Woohhyeok Jeong

  3. Department of Plastic and Reconstructive Surgery, Gyeongsang National University School of Medicine, Jinju, Republic of Korea

    Jun Sik Kim

  4. Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea

    Bae Kwon Jeong

  5. Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea

    Sung Chul Shin

  6. Department of Radiation Oncology, Keimyung University School of Medicine, Daegu, Republic of Korea

    Jin Hee Kim

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  1. Sang Woo Park
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  2. Jaehoon Choi
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  3. Junhyung Kim
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Correspondence to Jaehoon Choi.

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The authors declare that they have no conflict of interest.

Ethical approval

The university animal care committee for animal research of Gyeongsang National University approved the study protocol (GLA-101104-M0108).

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Informed consent was obtained from all individual participants included in the study.

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Park, S.W., Choi, J., Kim, J. et al. Anthocyanins from black soybean seed coat prevent radiation-induced skin fibrosis by downregulating TGF-β and Smad3 expression. Arch Dermatol Res 310, 401–412 (2018). https://doi.org/10.1007/s00403-018-1827-7

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  • DOI: https://doi.org/10.1007/s00403-018-1827-7

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