Skip to main content

Advertisement

SpringerLink
Log in

Protective effect and mechanism research of Phyllanthus emblica Linn. fruit extract on UV-induced photodamage in keratinocytes

  • Original Papers
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Ultraviolet (UV) irradiation causes acute and chronic cutaneous effects that may result in photodamage and photoaging. Epidermis keratinocytes, as the closest surface of skin, are susceptible to damage from UV rays. Phyllanthus emblica Linn. fruit (PE) extract, as a medicine and food dual-use plant, contains high levels of polyphenols and possesses multiple pharmacological properties. The present study investigated common and different molecular mechanisms and signaling pathway activations of UVA and UVB stimulated cell damage and photoprotective effect of PE extract against UVA and UVB by Methyl Thiazolyl Tetrazolium (MTT) method, Elisa assay, flow cytometry, differentially expressed genes analysis and western blot analysis. The results showed that UVA exposure (10 J/cm2) reduced HaCaT cell viability significantly, increased the apoptosis rate, elevated intracellular reactive oxygen species level and reduced antioxidant enzyme activities. And UVA irradiation could inhibit the ERK/TGF-β/Smad signaling pathway to downregulate collagen I, collagen III and elastin expressions, resulting in the photoaging of skin cells. We also found UVB exposure (30 mJ/cm2) caused HaCaT cell damage, promoted apoptosis, increased ROS production and induced the release of proinflammatory cytokines (IL-1α, IL-6 and PGE2). Further, in HaCaT cells, UVB ray was able to induce the activation of apoptosis markers (cleaved PARP1 and cleaved caspase3) through the MAPK/AP-1 signaling pathway using western blot analysis. Pre-treatment of PE extract prevented the UVA and UVB induced photoaging and injury in HaCaT cells through activation of ERK/TGF-β/Smad pathway and inhibition of MAPK/AP-1 pathway, respectively. Therefore, PE extract has the potential to be used as an oral and topical preparation against skin aging and injury induced by UVA and UVB.

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

Data availability

The original contributions generated for this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

References

  1. Wang, H., Wang, Y., Fu, F., Qian, Y., Xiao, Y., Yang, D., & Qiu, X. (2020). Controlled preparation of lignin/titanium dioxide hybrid composite particles with excellent UV aging resistance and its high value application. International Journal of Biological Macromolecules, 150, 371–379.

    Article  CAS  PubMed  Google Scholar 

  2. Svobodova, A., Walterova, D., & Vostalova, J. (2006). Ultraviolet light induced alteration to the skin. Biomedical Papers, 150, 25–28.

    Article  CAS  PubMed  Google Scholar 

  3. Muthusamy, V., & Piva, T. J. (2010). The UV response of the skin: A review of the MAPK, NFκB and TNFα signal transduction pathways. Archives of Dermatological Research, 302, 5–17.

    Article  CAS  PubMed  Google Scholar 

  4. Gallagher, R. P., & Lee, T. K. (2006). Adverse effects of ultraviolet radiation: a brief review. Progress in Biophysics and Molecular Biology, 92, 119–131.

    Article  CAS  PubMed  Google Scholar 

  5. Cezar, T. L., Martinez, R. M., Rocha, C. D., Melo, C. P., Vale, D. L., Borghi, S. M., Fattori, V., Vignoli, J. A., Camilios-Neto, D., & Baracat, M. M. (2019). Treatment with maresin 1, a docosahexaenoic acid-derived pro-resolution lipid, protects skin from inflammation and oxidative stress caused by UVB irradiation. Scientific Reports, 9, 1–14.

    Article  CAS  Google Scholar 

  6. Wenk, J., Brenneisen, P., Meewes, C., Wlaschek, M., Peters, T., Blaudschun, R., Ma, W., Kuhr, L., Schneider, L., & Kochanek, K. S. (2001). UV-induced oxidative stress and photoaging. Current Problems in Dermatology, 29, 83–94.

    Article  CAS  PubMed  Google Scholar 

  7. Kunkel, G. H., Chaturvedi, P., & Tyagi, S. C. (2016). Mitochondrial pathways to cardiac recovery: TFAM. Heart Failure Review, 21, 499–517.

    Article  CAS  Google Scholar 

  8. Danovaro, R., Bongiorni, L., Corinaldesi, C., Giovannelli, D., Damiani, E., Astolfi, P., Greci, L., & Pusceddu, A. (2008). Sunscreens cause coral bleaching by promoting viral infections. Health Perspectives, 116, 441–447.

    Article  CAS  Google Scholar 

  9. Parrado, C., Philips, N., Gilaberte, Y., Juarranz, A., & Gonzalez, S. (2018). Oral photoprotection: effective agents and potential candidates. Frontiers in Medicine, 5, 188–206.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhang, T., Huang, S., Qiu, J., Wu, X., Yuan, H., & Park, S. (2022). Beneficial effect of gastrodia elata blume and poria cocos wolf administration on acute UVB irradiation by alleviating inflammation through promoting the gut-skin axis. International Journal of Molecular Sciences, 23, 10833–10859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Heinrich, U., Neukam, K., Tronnier, H., Sies, H., & Stahl, W. (2006). Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women. Journal of Nutrition, 136, 1565–1569.

    Article  CAS  PubMed  Google Scholar 

  12. Gonzalez, S., Pathak, M., Cuevas, J., Villarrubia, V., & Fitzpatrick, T. (1997). Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin. Photodermatology, Photoimmunology and Photomedicine, 13, 50–60.

    Article  CAS  PubMed  Google Scholar 

  13. Kunchana, K., Jarisarapurin, W., Chularojmontri, L., & Wattanapitayakul, S. K. (2021). Potential use of amla (Phyllanthus emblica L.) fruit extract to protect skin keratinocytes from inflammation and apoptosis after UVB irradiation. Antioxidants, 10, 703–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kaur, S., & Muthuraman, A. (2019). Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice. Toxicology Reports, 6, 505–513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhou, Y. D., Fang, X. F., & Cui, Z. J. (2009). UVA-induced calcium oscillations in rat mast cells. Cell Calcium, 45, 18–28.

    Article  CAS  PubMed  Google Scholar 

  16. Bae, J. S., Han, M., Shin, H. S., Kim, M. K., Shin, C. Y., Lee, D. H., & Chung, J. H. (2017). Perilla frutescens leaves extract ameliorates ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin. Journal of Ethnopharmacology, 195, 334–342.

    Article  CAS  PubMed  Google Scholar 

  17. Fortes, G. B., Alves, L. S., Oliveira, R. D., Dutra, F. F., Rodrigues, D., Fernandez, P. L., Padron, T. S., De Rosa, M. J., Kelliher, M., & Golenbock, D. (2012). Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood, 119, 2368–2375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yu, X., Zhao, Q., Zhang, H., Fan, C., Zhang, X., Xie, Q., Xu, C., Liu, Y., Wu, X., & Han, Q. (2016). Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages. Acta Biochimica et Biophysica Sinica, 48, 454–461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. FitzGerald, G., & Ricciotti, E. (2011). Prostaglandins and inflammation. Arteriosclerosis, 31, 986–1000.

    Article  Google Scholar 

  20. Obermajer, N., & Kalinski, P. (2012). Key role of the positive feedback between PGE2 and COX2 in the biology of myeloid-derived suppressor cells. Oncoimmunology, 1, 762–764.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zhao Q, Chen Y, Qu L (2022) Combined Transcriptomic and proteomic analyses reveal the different responses to UVA and UVB radiation in human Keratinocytes. Photochemistry and Photobiolog 1–16

  22. Plotnikov, A., Zehorai, E., Procaccia, S., & Seger, R. (1813). The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. Acta - Molecular Cell Research, 2011, 1619–1633.

    Google Scholar 

  23. Delmastro, M. M., & Piganelli, J. D. (2011). Oxidative stress and redox modulation potential in type 1 diabetes. Clinical and Developmental Immunology, 2011, 1–15.

    Article  Google Scholar 

  24. Kumar, P., Natarajan, K., & Shanmugam, N. (2014). High glucose driven expression of pro-inflammatory cytokine and chemokine genes in lymphocytes: molecular mechanisms of IL-17 family gene expression. Cellular Signalling, 26, 528–539.

    Article  CAS  PubMed  Google Scholar 

  25. Shono, Y., Tuckett, A. Z., Liou, H. C., Doubrovina, E., Derenzini, E., Ouk, S., Tsai, J. J., Smith, O. M., Levy, E. R., & Kreines, F. M. (2016). Characterization of a c-Rel inhibitor that mediates anticancer properties in hematologic malignancies by blocking NF-κB–controlled oxidative stress responses. Cancer Research, 76, 377–389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu, H., Lu, J., Hua, Y., Zhang, P., Liang, Z., Ruan, L., Lian, C., Shi, H., Chen, K., & Tu, Z. (2015). Targeting heat-shock protein 90 with ganetespib for molecularly targeted therapy of gastric cancer. Cell Death & Disease, 6, e1595–e1595.

    Article  CAS  Google Scholar 

  27. Kittler, R., Putz, G., Pelletier, L., Poser, I., Heninger, A. K., Drechsel, D., Fischer, S., Konstantinova, I., Habermann, B., & Grabner, H. (2004). An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature, 432, 1036–1040.

    Article  CAS  PubMed  Google Scholar 

  28. Yamada, H., & Rao, C. (2010). Genes that modulate the sensitivity for anti-microtubule drug-mediated chemotherapy. Current Cancer Drug Targets, 10, 623–633.

    Article  CAS  PubMed  Google Scholar 

  29. Gurunathan, S., Qasim, M., Park, C. H., Iqbal, M. A., Yoo, H., Hwang, J. H., Uhm, S. J., Song, H., Park, C., & Choi, Y. (2019). Cytotoxicity and transcriptomic analyses of biogenic palladium nanoparticles in human ovarian cancer cells (SKOV3). Nanomaterials, 9, 787–810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim, J., Lee, C. W., Kim, E. K., Lee, S. J., Park, N. H., Kim, H. S., Kim, H. K., Char, K., Jang, Y. P., & Kim, J. W. (2011). Inhibition effect of Gynura procumbens extract on UV-B-induced matrix-metalloproteinase expression in human dermal fibroblasts. Journal of Ethnopharmacology, 137, 427–433.

    Article  PubMed  Google Scholar 

  31. Quan, T., Qin, Z., Xia, W., Shao, Y., Voorhees, J. J., & Fisher, G. J. (2009). Matrix-degrading metalloproteinases in photoaging. Journal of Investigative Dermatology Symposium Proceedings, 14, 20–24.

    Article  CAS  PubMed  Google Scholar 

  32. Verrecchia, F., Chu, M. L., & Mauviel, A. (2001). Identification of novel TGF-β/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. Journal of Biological Chemistry, 276, 17058–17062.

    Article  CAS  PubMed  Google Scholar 

  33. Wada, T., & Penninger, J. M. (2004). Mitogen-activated protein kinases in apoptosis regulation. Oncogene, 23, 2838–2849.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang, Y. E. (2017). Non-Smad signaling pathways of the TGF-β family. Cold Spring Harbor Perspectives in Biology, 9, a022129–a022149.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wang, S. Q., Stanfield, J. W., & Osterwalder, U. (2008). In vitro assessments of UVA protection by popular sunscreens available in the United States. Journal of the American Academy of Dermatology, 59, 934–942.

    Article  PubMed  Google Scholar 

  36. Wang, S. Q., Balagula, Y., & Osterwalder, U. (2010). Photoprotection: a review of the current and future technologies. Dermatologic Therapy, 23, 31–47.

    Article  CAS  PubMed  Google Scholar 

  37. Zou, W., González, A., Jampaiah, D., Ramanathan, R., Taha, M., Walia, S., Sriram, S., Bhaskaran, M., Dominguez-Vera, J. M., & Bansal, V. (2018). Skin color-specific and spectrally-selective naked-eye dosimetry of UVA, B and C radiations. Nature Communications, 9, 1–10.

    Article  Google Scholar 

  38. Perianayagam, J. B., Sharma, S., Joseph, A., & Christina, A. (2004). Evaluation of anti-pyretic and analgesic activity of Emblica officinalis Gaertn. Journal of Ethnopharmacology, 95, 83–85.

    Article  PubMed  Google Scholar 

  39. Mrakic-Sposta, S., Gussoni, M., Vezzoli, A., Dellanoce, C., Comassi, M., Giardini, G., Bruno, R. M., Montorsi, M., Corciu, A., & Greco, F. (2020). Acute effects of triathlon race on oxidative stress biomarkers. Oxidative Medicine and Cellular Longevity, 2020, 1–14.

    Article  Google Scholar 

  40. Kuechle, M. K., & Elkon, K. B. (2017). Shining light on lupus and UV. Arthritis Research and Therapy, 9, 1–3.

    Google Scholar 

  41. Xiao, Y., Ren, Q., & Wu, L. (2022). The pharmacokinetic property and pharmacological activity of acteoside: a review. Biomedicine & Pharmacotherapy, 153, 113296–113309.

    Article  CAS  Google Scholar 

  42. Huguier, V., Giot, J. P., Simonneau, M., Levillain, P., Charreau, S., Garcia, M., Jégou, J. F., Bodet, C., Morel, F., & Lecron, J. C. (2019). Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers. Scientific Reports, 9, 1–10.

    Article  CAS  Google Scholar 

  43. Wang, X. P., Schunck, M., Kallen, K. J., Neumann, C., Trautwein, C., Rose-John, S., & Proksch, E. (2004). The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. Journal of Investigative Dermatology, 123, 124–131.

    Article  CAS  PubMed  Google Scholar 

  44. Funk, C. D. (2001). Prostaglandins and leukotrienes: advances in eicosanoid biology. Science, 294, 1871–1875.

    Article  CAS  PubMed  Google Scholar 

  45. Torres, M., & Forman, H. J. (2003). Redox signaling and the MAP kinase pathways. BioFactors, 17, 287–296.

    Article  CAS  PubMed  Google Scholar 

  46. Xiao, X., Wu, Z. C., & Chou, K. C. (2011). A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites. PLoS One, 6, e20592–e20602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chaikul, P., Kanlayavattanakul, M., Somkumnerd, J., Lourith, N. J. J. O. T., & Medicine, C. (2021). Phyllanthus emblica L. (amla) branch: a safe and effective ingredient against skin aging. Journal of Traditional and Complementary Medicine, 11, 390–399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bandyopadhyay, S. K., Pakrashi, S. C., & Pakrashi, A. J. J. O. E. (2000). The role of antioxidant activity of Phyllanthus emblica fruits on prevention from indomethacin induced gastric ulcer. Journal of Ethnopharmacology, 70, 171–176.

    Article  CAS  PubMed  Google Scholar 

  49. Majeed, M., Bhat, B., Anand, S., Sivakumar, A., Paliwal, P., & Geetha, K. G. (2011). Inhibition of UV-induced ROS and collagen damage by Phyllanthus emblica extract in normal human dermal fibroblasts. Journal of Cosmetic Science, 62, 49–57.

    PubMed  Google Scholar 

  50. Lin, Y. Y., Lu, S. H., Gao, R., Kuo, C. H., Chung, W. H., Lien, W. C., Wu, C. C., Diao, Y., Wang, H.-M.D.J.O.M., & Longevity, C. (2021). A novel biocompatible herbal extract-loaded hydrogel for acne treatment and repair. Oxidative Medicine and Cellular Longevity, 2021, 1–13.

    Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge funding from independent research fund of Yunnan Characteristic Plant Extraction Laboratory (2022YKZY001 and 2022YKZY003).

Author information

Authors and Affiliations

  1. Innovation Materials Research and Development Center, Botanee Research Institute, Shanghai Jiyan Bio-Pharmaceutical Development Co., Ltd., Shanghai, 201702, China

    Liping Qu, Feifei Wang & Yueyue Chen

  2. Yunnan Characteristic Plant Extraction Laboratory, Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming, 650106, China

    Liping Qu & Feifei Wang

  3. Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming, 650106, China

    Liping Qu & Feifei Wang

Authors
  1. Liping Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feifei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yueyue Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YC and LQ designed the experiments. LQ performed the experiments and analyzed the data. YC and FW wrote the paper. All authors discussed and approved the final manuscript.

Corresponding author

Correspondence to Yueyue Chen.

Ethics declarations

Conflict of interest

The authors declare no competing financial interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 544 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qu, L., Wang, F. & Chen, Y. Protective effect and mechanism research of Phyllanthus emblica Linn. fruit extract on UV-induced photodamage in keratinocytes. Photochem Photobiol Sci 22, 1945–1959 (2023). https://doi.org/10.1007/s43630-023-00423-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43630-023-00423-3

Keywords

Search

Navigation