Selenium Added Unripe Carica Papaya Pulp Extracts Enhance Wound Repair Through TGF-β1 and VEGF-a Signalling Pathway

Overview

Journal BMC Complement Altern Med

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2015 Oct 17

PMID 26471293

Citations 11

Authors

Abdulrazaq Bidemi Nafiu

Mohammad Tariqur Rahman

Affiliations

Soon will be listed here.

Abstract

Background: Increased wound healing efficiency by Se(2+) added Carica papaya L. (Caricaceae) fruit extract was linked to increased antioxidant and anti-inflammatory responses during healing. We investigated the impact of Se(2+) or Zn(2+) added papaya water (WE) and phosphate-buffered saline (PE) extracts on cells recruitment and bio-molecular alterations on days 4 and 10 post wounding in an in vivo excision wound.

Methods: Excision wounds were created on the dorsum of Sprague Dawley rats and treated topically twice/day with 20 μL of PE and WE (5 mg extract/mL), 0.5 μgSe(2+) added PE and WE (PES and WES), or 100 μMZn(2+) added PE and WE (PEZ and WEZ). Deionised water (negative) and Solcoseryl (positive) were applied on the control groups. Histochemical and biochemical assays were used to evaluate cellular and bio-molecular changes in the wound.

Results: PES (PE + 0.5 μg Se(2+)) only increased significantly (p < 0.05) wound total protein content (95.14 ± 1.15 mg/g tissue vs positive control; 80.42 ± 0.86 mg/g tissue) on day 10 post wounding. PES increased significantly (p < 0.05) the number of fibroblasts/high power field (HPF) (75.60 ± 9.66) but decreased significantly (p < 0.05) the number of polymorphonuclear leukocytes/HPF (59.20 ± 12.64) in the wound compared to positive control (50.60 ± 12.58 fibroblasts/HPF, 101.00 ± 27.99 polymorphonuclear leukocytes/HPF) on day 4. Similar results were recorded for WES. PES demonstrated increased neovascularization, TGF-β1 and VEGFA expressions at day 4 and increased collagen at day 10.

Conclusion: Papaya extract improved wound repair by increasing fibroblasts recruitment and reducing polymorphonuclear leukocytes infiltration through early transient expressions of TGF-β1 and VEGFA at the wound area. The processes were amplified with Se(2+) addition.

Citing Articles

Selenium Enhances the Growth of Bovine Endometrial Stromal Cells by PI3K/AKT/GSK-3β and Wnt/β-Catenin Pathways.

Dong J, Wang Z, Fei F, Jiang Y, Jiang Y, Guo L Vet Sci. 2024; 11(12).

PMID: 39729014 PMC: 11680133. DOI: 10.3390/vetsci11120674.

The effect of selenium on the proliferation of bovine endometrial epithelial cells in a lipopolysaccharide-induced damage model.

Li H, Wang H, Cui L, Liu K, Guo L, Li J BMC Vet Res. 2024; 20(1):109.

PMID: 38500165 PMC: 10946195. DOI: 10.1186/s12917-024-03958-4.

Assessment of wound healing activity in diabetic mice treated with a novel therapeutic combination of selenium nanoparticles and platelets rich plasma.

Karas R, Alexeree S, Elsayed H, Attia Y Sci Rep. 2024; 14(1):5346.

PMID: 38438431 PMC: 10912747. DOI: 10.1038/s41598-024-54064-2.

The effect and mechanism of selenium supplementation on the proliferation capacity of bovine endometrial epithelial cells exposed to lipopolysaccharide in vitro under high cortisol background.

Li H, Dong J, Cui L, Liu K, Guo L, Li J J Anim Sci. 2024; 102.

PMID: 38289713 PMC: 10889726. DOI: 10.1093/jas/skae021.

Sodium selenite preserves rBM-MSCs' stemness, differentiation potential, and immunophenotype and protects them against oxidative stress via activation of the Nrf2 signaling pathway.

Rahimi B, Panahi M, Lotfi H, Khalili M, Salehi A, Saraygord-Afshari N BMC Complement Med Ther. 2023; 23(1):131.

PMID: 37098557 PMC: 10127330. DOI: 10.1186/s12906-023-03952-7.

References

BOAS N . Method for the determination of hexosamines in tissues. J Biol Chem. 1953; 204(2):553-63. View

Gurung S, Skalko-Basnet N . Wound healing properties of Carica papaya latex: in vivo evaluation in mice burn model. J Ethnopharmacol. 2008; 121(2):338-41. DOI: 10.1016/j.jep.2008.10.030. View

McKenzie R, Arthur J, Beckett G . Selenium and the regulation of cell signaling, growth, and survival: molecular and mechanistic aspects. Antioxid Redox Signal. 2002; 4(2):339-51. DOI: 10.1089/152308602753666398. View

Kasuya A, Tokura Y . Attempts to accelerate wound healing. J Dermatol Sci. 2014; 76(3):169-72. DOI: 10.1016/j.jdermsci.2014.11.001. View

Hershfinkel M, Silverman W, Sekler I . The zinc sensing receptor, a link between zinc and cell signaling. Mol Med. 2007; 13(7-8):331-6. PMC: 1952663. DOI: 10.2119/2006-00038.Hershfinkel. View

Bayat M, Asgari-Moghadam Z, Maroufi M, Rezaie F, Bayat M, Rakhshan M . Experimental wound healing using microamperage electrical stimulation in rabbits. J Rehabil Res Dev. 2006; 43(2):219-26. DOI: 10.1682/jrrd.2005.05.0089. View

Derici H, Yaman I, Kara C, Kamer E, Diniz G, Ortac R . Simvastatin improves incisional wound healing in a rat model: an experimental study. Wounds. 2015; 24(7):195-200. View

Gamelli R, He L . Incisional wound healing. Model and analysis of wound breaking strength. Methods Mol Med. 2003; 78:37-54. DOI: 10.1385/1-59259-332-1:037. View

Lim Y, Levy M, Bray T . Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice. J Nutr. 2004; 134(4):811-6. DOI: 10.1093/jn/134.4.811. View

10.

Anuar N, Zahari S, Taib I, Rahman M . Effect of green and ripe Carica papaya epicarp extracts on wound healing and during pregnancy. Food Chem Toxicol. 2008; 46(7):2384-9. DOI: 10.1016/j.fct.2008.03.025. View

11.

McAuslan B, Reilly W . Selenium-induced cell migration and proliferation: relevance to angiogenesis and microangiopathy. Microvasc Res. 1986; 32(1):112-20. DOI: 10.1016/0026-2862(86)90047-6. View

12.

Bruun J, Nielsen C, Pedersen S, Flyvbjerg A, Richelsen B . Estrogen reduces pro-inflammatory cytokines in rodent adipose tissue: studies in vivo and in vitro. Horm Metab Res. 2003; 35(3):142-6. DOI: 10.1055/s-2003-39074. View

13.

Dandrea M, Rogahn C, Damiano B, Andrade-Gordon P . A combined histochemical and double immunohistochemical labeling protocol for simultaneous evaluation of four cellular markers in restenotic arteries. Biotech Histochem. 1999; 74(4):172-80. DOI: 10.3109/10520299909047971. View

14.

Azarkan M, El Moussaoui A, van Wuytswinkel D, Dehon G, Looze Y . Fractionation and purification of the enzymes stored in the latex of Carica papaya. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 790(1-2):229-38. DOI: 10.1016/s1570-0232(03)00084-9. View

15.

Berger M, Binnert C, Chiolero R, Taylor W, Raffoul W, Cayeux M . Trace element supplementation after major burns increases burned skin trace element concentrations and modulates local protein metabolism but not whole-body substrate metabolism. Am J Clin Nutr. 2007; 85(5):1301-6. DOI: 10.1093/ajcn/85.5.1301. View

16.

Starley I, Mohammed P, Schneider G, Bickler S . The treatment of paediatric burns using topical papaya. Burns. 1999; 25(7):636-9. DOI: 10.1016/s0305-4179(99)00056-x. View

17.

Nafiu A, Rahman M . Anti-inflammatory and antioxidant properties of unripe papaya extract in an excision wound model. Pharm Biol. 2014; 53(5):662-71. DOI: 10.3109/13880209.2014.936470. View

18.

Ashcroft G, Mills S, Lei K, Gibbons L, Jeong M, Taniguchi M . Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor. J Clin Invest. 2003; 111(9):1309-18. PMC: 154440. DOI: 10.1172/JCI16288. View

19.

Otranto M, Souza-Netto I, Aguila M, Monte-Alto-Costa A . Male and female rats with severe protein restriction present delayed wound healing. Appl Physiol Nutr Metab. 2009; 34(6):1023-31. DOI: 10.1139/H09-100. View

20.

Midwood K, Williams L, Schwarzbauer J . Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol. 2004; 36(6):1031-7. DOI: 10.1016/j.biocel.2003.12.003. View