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Pluronic F127-liposome-encapsulated curcumin activates Nrf2/Keap1 signaling pathway to promote cell migration of HaCaT cells

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Abstract

Curcumin (CUR) is an extract of Curcuma longa Linn., which has various pharmacological activities. The instability, low water solubility and bioavailability of CUR greatly limit its clinical application. This work prepared Pluronic F127-liposome-encapsulated curcumin (CUR-LIP-F127) and explored its functional role in wound healing. Liposome-encapsulated curcumin (CUR-LIP) and CUR-LIP-F127 were prepared. Human keratinocyte cell line (HaCaT) was treated with CUR, Pluronic F127-liposome (LIP-F127) and CUR-LIP-F127, or combined with ML385 (Nrf2 inhibitor). The expression of mRNAs and proteins was detected by quantitative real-time PCR and western blotting. MTT and wound healing assays were performed to detect cell viability and migration. CUR, LIP-F127 and CUR-LIP-F127 all had no influence on cell viability of HaCaT cells. CUR-LIP-F127 treatment significantly accelerated cell migration and enhanced the expression of nuclear factor erythroid-related factor 2 (Nrf2) and kelch-like erythroid cell-derived protein 1 (Keap1) in HaCaT cells with respect to CUR or LIP-F127 treatment. ML385 treatment impaired CUR-LIP-F127-mediated promotion of migration and up-regulation of Nrf2 and Keap1 in HaCaT cells. This work demonstrated that CUR-LIP-F127 activated Nrf2/Keap1 signaling pathway to promote migration of HaCaT cells, suggesting that CUR-LIP-F127 may contribute to wound healing.

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References

  1. Zomer H, Trentin A (2018) Skin wound healing in humans and mice: challenges in translational research. J Dermatol Sci 90:3–12. https://doi.org/10.1016/j.jdermsci.2017.12.009

    Article  Google Scholar 

  2. Monavarian M, Kader S, Moeinzadeh S, Jabbari E (2019) Regenerative scar-free skin wound healing. Tissue engineering. Part B, Rev 25:294–311. https://doi.org/10.1089/ten.TEB.2018.0350

    Article  Google Scholar 

  3. Martin R (2020) Wound healing. Surgical Clin North America 100:ix–xi. https://doi.org/10.1016/j.suc.2020.05.012

    Article  Google Scholar 

  4. Sorg H, Tilkorn D, Hager S, Hauser J, Mirastschijski U (2017) Skin wound healing: an update on the current knowledge and concepts. European surgical research. Europaische chirurgische Forschung Recherches chirurgicales europeennes 58:81–94. https://doi.org/10.1159/000454919

    Article  Google Scholar 

  5. Grabowski G, Pacana M, Chen E (2020) Keloid and hypertrophic scar formation, prevention, and management: standard review of abnormal scarring in orthopaedic surgery. J Am Acad Orthop Surg 28:e408–e414. https://doi.org/10.5435/jaaos-d-19-00690

    Article  Google Scholar 

  6. Rodrigues M, Kosaric N, Bonham C, Gurtner G (2019) Wound healing: a cellular perspective. Physiol Rev 99:665–706. https://doi.org/10.1152/physrev.00067.2017

    Article  CAS  Google Scholar 

  7. Everts P, Onishi K, Jayaram P, Lana J, Mautner K (2020) Platelet-rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci. https://doi.org/10.3390/ijms21207794

    Article  Google Scholar 

  8. Gauglitz G, Zedler S, von Spiegel F, Fuhr J, von Donnersmarck G, Faist E (2012) Functional characterization of cultured keratinocytes after acute cutaneous burn injury. PLoS ONE 7:e29942. https://doi.org/10.1371/journal.pone.0029942

    Article  CAS  Google Scholar 

  9. Jiang Z, Wei J, Yang W, Li W, Liu F, Yan X, Yan X, Hu N, Li J (2020) MicroRNA-26a inhibits wound healing through decreased keratinocytes migration by regulating ITGA5 through PI3K/AKT signaling pathway. Biosci Rep. https://doi.org/10.1042/bsr20201361

  10. Koike Y, Yozaki M, Utani A, Murota H (2020) Fibroblast growth factor 2 accelerates the epithelial-mesenchymal transition in keratinocytes during wound healing process. Sci Rep 10:18545. https://doi.org/10.1038/s41598-020-75584-7

    Article  CAS  Google Scholar 

  11. Kotha R, Luthria D (2019) Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules (Basel, Switzerland). https://doi.org/10.3390/molecules24162930

    Article  Google Scholar 

  12. Kim Y, Clifton P (2018) Curcumin, cardiometabolic health and dementia. Int J Environ Res Public Health. https://doi.org/10.3390/ijerph15102093

    Article  Google Scholar 

  13. Burge K, Gunasekaran A, Eckert J, Chaaban H (2019) Curcumin and intestinal inflammatory diseases: molecular mechanisms of protection. Int J Mol Sci. https://doi.org/10.3390/ijms20081912

    Article  Google Scholar 

  14. Dei Cas M, Ghidoni R (2019) Dietary curcumin: correlation between bioavailability and health potential. Nutrients. https://doi.org/10.3390/nu11092147

    Article  Google Scholar 

  15. Ipar V, Dsouza A, Devarajan P (2019) Enhancing curcumin oral bioavailability through nanoformulations. Eur J Drug Metab Pharmacokinet 44:459–480. https://doi.org/10.1007/s13318-019-00545-z

    Article  CAS  Google Scholar 

  16. Feng T, Wei Y, Lee R, Zhao L (2017) Liposomal curcumin and its application in cancer. Int J Nanomed 12:6027–6044. https://doi.org/10.2147/ijn.s132434

    Article  CAS  Google Scholar 

  17. Rabbani P, Soares M, Hameedi S, Kadle R, Mubasher A, Kowzun M, Ceradini D (2019) Dysregulation of Nrf2/Keap1 redox pathway in diabetes affects multipotency of stromal cells. Diabetes 68:141–155. https://doi.org/10.2337/db18-0232

    Article  CAS  Google Scholar 

  18. Rabbani P, Abdou S, Sultan D, Kwong J, Duckworth A, Ceradini D (2018) In Vivo imaging of reactive oxygen species in a murine wound model. JoVE. https://doi.org/10.3791/58450

    Article  Google Scholar 

  19. Lin L, Li C, Zhang D, Yuan M, Chen C, Li M (2020) Synergic effects of berberine and curcumin on improving cognitive function in an Alzheimer’s disease mouse model. Neurochem Res 45:1130–1141. https://doi.org/10.1007/s11064-020-02992-6

    Article  CAS  Google Scholar 

  20. El Nebrisi E, Javed H, Ojha S, Oz M, Shehab S (2020) Neuroprotective effect of curcumin on the nigrostriatal pathway in a 6-hydroxydopmine-induced rat model of Parkinson’s disease is mediated by α7-nicotinic receptors. Int J Mol Sci. https://doi.org/10.3390/ijms21197329

    Article  Google Scholar 

  21. Zheng Y, Yang X, Tan J, Tian R, Shen P, Cai W, Liao H (2021) Curcumin suppresses the stemness of non-small cell lung cancer cells via promoting the nuclear-cytoplasm translocation of TAZ. Environ Toxicol 36:1135–1142. https://doi.org/10.1002/tox.23112

    Article  CAS  Google Scholar 

  22. Shabeeb D, Musa A, Abd Ali H, Najafi M (2020) Curcumin protects against radiotherapy-induced oxidative injury to the skin. Drug Des Dev Ther 14:3159–3163. https://doi.org/10.2147/dddt.s265228

    Article  CAS  Google Scholar 

  23. Kim D, Choi C, Park J, Lee S (2020) Nanospheres loaded with curcumin improve the bioactivity of umbilical cord blood-mesenchymal stem cells via C-SRC activation during the skin wound healing process. Cells. https://doi.org/10.3390/cells9061467

    Article  Google Scholar 

  24. Kamar S, Abdel-Kader D, Rashed L (2019) Beneficial effect of Curcumin Nanoparticles-Hydrogel on excisional skin wound healing in type-I diabetic rat: histological and immunohistochemical studies. Ann Anatomy 222:94–102. https://doi.org/10.1016/j.aanat.2018.11.005

    Article  Google Scholar 

  25. Orsu P, Haider H, Koyyada A (2021) Bioengineering for curcumin loaded carboxymethyl guargum/reduced graphene oxide nanocomposites for chronic wound healing applications. Int J Pharm 606:120928. https://doi.org/10.1016/j.ijpharm.2021.120928

    Article  CAS  Google Scholar 

  26. Abbas M, Hussain T, Arshad M, Ansari A, Irshad A, Nisar J, Hussain F, Masood N, Nazir A, Iqbal M (2019) Wound healing potential of curcumin cross-linked chitosan/polyvinyl alcohol. Int J Biol Macromol 140:871–876. https://doi.org/10.1016/j.ijbiomac.2019.08.153

    Article  CAS  Google Scholar 

  27. Sajadimajd S, Khazaei M (2018) Oxidative stress and cancer: the role of Nrf2. Curr Cancer Drug Targets 18:538–557. https://doi.org/10.2174/1568009617666171002144228

    Article  CAS  Google Scholar 

  28. Liu H, Xu X, Wu R, Bi L, Zhang C, Chen H, Yang Y (2021) Antioral squamous cell carcinoma effects of carvacrol via inhibiting inflammation, proliferation, and migration related to Nrf2/Keap1 pathway. Biomed Res Int 2021:6616547. https://doi.org/10.1155/2021/6616547

    Article  CAS  Google Scholar 

  29. Li P, Liu X, Xing W, Qiu H, Li R, Liu S, Sun H (2022) Exosome-derived miR-200a promotes esophageal cancer cell proliferation and migration via the mediating Keap1 expression. Mol Cell Biochem 477:1295–1308. https://doi.org/10.1007/s11010-022-04353-z

    Article  CAS  Google Scholar 

  30. Valcarcel-Ares M, Gautam T, Warrington J, Bailey-Downs L, Sosnowska D, de Cabo R, Losonczy G, Sonntag W, Ungvari Z, Csiszar A (2012) Disruption of Nrf2 signaling impairs angiogenic capacity of endothelial cells: implications for microvascular aging. J Gerontol Series A, Biol Sci Med Sci 67:821–829. https://doi.org/10.1093/gerona/glr229

    Article  CAS  Google Scholar 

  31. Hayashi R, Himori N, Taguchi K, Ishikawa Y, Uesugi K, Ito M, Duncan T, Tsujikawa M, Nakazawa T, Yamamoto M, Nishida K (2013) The role of the Nrf2-mediated defense system in corneal epithelial wound healing. Free Radical Biol Med 61:333–342. https://doi.org/10.1016/j.freeradbiomed.2013.04.008

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by Hunan Provincial Health Commission (202104101005) and Hunan Administration of traditional Chinese Medicine (2021227).

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Authors and Affiliations

  1. Department of Emergency, The First Hospital of Hunan University of Chinese MedicineYuhua DistrictHunan Province, No. 95, Shaoshan Middle Road, Changsha, 410000, People’s Republic of China

    Quan Zhou & Youliang Zhou

  2. Department of Orthopaedic, The First Hospital of Hunan University of Chinese Medicine, Hunan Province, Changsha, 410000, People’s Republic of China

    Xu Cai

  3. Department of Neurosurgery, Guangdong Province, Shenzhen Sami International Medical Center, Shenzhen, 518038, People’s Republic of China

    Ying Huang

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  1. Quan Zhou
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  2. Xu Cai
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  3. Ying Huang
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Contributions

QZ: Conceptualization, Methodology, Supervision, Writing- Original draft preparation, Investigation, Writing- Reviewing and Editing. XC: Data curation, Software. YH: Visualization, Validation. YZ: Conceptualization, Supervision, Writing- Original draft preparation, Writing- Reviewing and Editing.

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Correspondence to Youliang Zhou.

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Zhou, Q., Cai, X., Huang, Y. et al. Pluronic F127-liposome-encapsulated curcumin activates Nrf2/Keap1 signaling pathway to promote cell migration of HaCaT cells. Mol Cell Biochem 478, 241–247 (2023). https://doi.org/10.1007/s11010-022-04481-6

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