Epidermal Stem Cell in Wound Healing of Gliricidia sepium Leaves from Indonesia and the Philippines in Rats (Rattus norvegicus)

Authors

  • Aulanni’am Aulanni’am Biochemistry Laboratory
  • Ricadonna Raissa Biochemistry Laboratory, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia
  • Wibi Riawan Department of Molecular and Biochemistry, Faculty of Medicine, Brawijaya University, Malang, Indonesia https://orcid.org/0000-0001-5027-5051
  • Dyah Kinasih Wuragil Laboratory of Veterinary Biochemistry, Faculty of Veterinary Medicine, Brawijaya University, Malang, Indonesia
  • Fajar Shodiq Permata Laboratory of Veterinary Histology, Faculty of Veterinary Medicine, Brawijaya University, Malang, Indonesia
  • Ma Asuncion Guiang Beltran Department of Microbiology and Veterinary Public Health, College of Veterinary Medicine, Tarlac Agricultural University, Tarlac, Republic of the Philippines

DOI:

https://doi.org/10.3889/oamjms.2022.8637

Keywords:

Gliricidia sepium leaves, Wound healing, Epidermal, Stem cell, Herbal plant

Abstract

AIM: This study intended to investigate the regenerate wound, due to the ointment therapy containing Gliricidia sepium leaves that has potential-induced epidermal stem cells producing. It determined its effect on the expression of transforming growth factor-β1 (TGF-β1), Smad-3, β-catenin, LGR-6.

MATERIALS AND METHODS: About 16 Wistar male rats aged approximately 2 months (150–200g) were used and were divided into four treatment groups (T1, positive control; T2, negative control; T3, wounds treated with G. sepium from Indonesia; and T4, wounds treated with G. sepium from the Philippines). The treatment of ointment was applied to the wound for 3 days. The expression of TGF-β1, Smad-3, β-catenin, and LGR-6 was observed by immunohistochemistry staining.

RESULTS: G. sepium leaves significantly (p < 0.05) upregulated the expression of TGF-β1, Smad-3, β-catenin, and LGR-6 in the group treated with Indonesian G. sepium leaves were higher than that in the group treated with G. sepium leaves from the Philippines.

CONCLUSIONS: Both leaves Varian contain flavonoids, saponins, and tannins, which act as producing epidermal stem cell agents to enhance the wound healing process. It can be concluded that both Gl. sepium Varian Indonesia and the Philippines have a potential effect on wound healing.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Gonzalez AC, Costa TF, Andrade ZA, Medrado AR. Wound healing – A literature review. An Bras Dermatol. 2016;91(5):614-20. https://doi.org/10.1590/abd1806-4841.20164741 PMid:27828635 DOI: https://doi.org/10.1590/abd1806-4841.20164741

Coalson E, Bishop E, Liu W, Feng Y, Spezia M, Liu B, et al. Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside. Genes Dis. 2019;6(4):342-58. https://doi.org/10.1016/j.gendis.2019.09.008 PMid:31832514 DOI: https://doi.org/10.1016/j.gendis.2019.09.008

Cañedo-Dorantes L, Cañedo-Ayala M. Skin Acute wound healing: A comprehensive review. Int J Inflam. 2019;2019:3706315. https://doi.org/10.1155/2019/3706315 PMid:31275545 DOI: https://doi.org/10.1155/2019/3706315

Rodrigues M, Kosaric N, Bonham CA, Gurtner GC. Wound healing: A cellular perspective. Physiol Rev. 2019;99(1):665-706. https://doi.org/10.1152/physrev.00067.2017 PMid:30475656 DOI: https://doi.org/10.1152/physrev.00067.2017

Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: An update on the current knowledge and concepts. Eur Surg Res. 2017;58(1-2):81-94. https://doi.org/10.1159/000454919 PMid:27974711 DOI: https://doi.org/10.1159/000454919

Teng M, Huang Y, Zhang H. Application of stems cells in wound healing – An update. Wound Repair Regen. 2014;22(2):151-60. https://doi.org/10.1111/wrr.12152 PMid:24635168 DOI: https://doi.org/10.1111/wrr.12152

Watt FM, Collins CA. Role of beta-catenin in epidermal stem cell expansion, lineage selection, and cancer. Cold Spring Harb Symp Quant Biol. 2008;73:503-12. https://doi.org/10.1101/sqb.2008.73.011 PMid:19022747 DOI: https://doi.org/10.1101/sqb.2008.73.011

Sakaki-Yumoto M, Katsuno Y, Derynck R. TGF-β family signaling in stem cells. Biochim Biophys Acta. 2013;1830(2):2280-96. https://doi.org/10.1016/j.bbagen.2012.08.008 PMid:22959078 DOI: https://doi.org/10.1016/j.bbagen.2012.08.008

Shi X, DiRenzo D, Guo LW, Franco SR, Wang B, Seedial S, et al. TGF-β/Smad3 stimulates stem cell/developmental gene expression and vascular smooth muscle cell de-differentiation. PLoS One. 2014;9(4):e93995. https://doi.org/10.1371/journal.pone.0093995 PMid:24718260 DOI: https://doi.org/10.1371/journal.pone.0093995

Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O. Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci. 2015;16(10):25476-501. https://doi.org/10.3390/ijms161025476 PMid:26512657 DOI: https://doi.org/10.3390/ijms161025476

Lichtenberger B, Mastrogiannaki M, Watt F. Epidermal β-catenin activation remodels the dermis via paracrine signalling to distinct fibroblast lineages. Nat Commun 2016;7:10537. https://doi.org/10.1038/ncomms10537 PMid:26837596 DOI: https://doi.org/10.1038/ncomms10537

Wang PH, Huang BS, Horng HC, Yeh CC, Chen YJ. Wound healing. J Chin Med Assoc. 2018;81(2):94-101. https://doi.org/10.1016/J.JCMA.2017.11.002 PMid:29169897 DOI: https://doi.org/10.1016/j.jcma.2017.11.002

Yang R, Liu F, Wang J, Chen X, Xie J, Xiong K. Epidermal stem cells in wound healing and their clinical applications. Stem Cell Res Ther. 2019;10(1):229. https://doi.org/10.1186/s13287-019-1312-z PMid:31358069 DOI: https://doi.org/10.1186/s13287-019-1312-z

Park SR, Lee JH, Kim PH. Smad3 and Smad4 mediate transforming growth factor-beta1-induced IgA expression in murine B lymphocytes. Eur J Immunol. 2001;31(6):1706-15. https://doi.org/10.1002/1521-4141(200106)31:6<1706:aid-immu1706>3.0.co;2-z PMid:11385614 DOI: https://doi.org/10.1002/1521-4141(200106)31:6<1706::AID-IMMU1706>3.0.CO;2-Z

Jian H, Shen X, Liu I, Semenov M, He X, Wang XF. Smad3- dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes Dev. 2006;20(6):666- 74. https://doi.org/10.1101/gad.1388806 PMid:16543220 DOI: https://doi.org/10.1101/gad.1388806

Penn JW, Grobbelaar AO, Rolfe KJ. The role of the TGF-β family in wound healing, burns and scarring: A review. Int J Burns Trauma. 2012;2(1):18-28. PMid:3415964

Walton KL, Johnson KE, Harrison CA. Targeting TGF-β mediated SMAD signaling for the prevention of fibrosis. Front Pharmacol. 2017;8:461. https://doi.org/10.3389/fphar.2017.00461 PMid:28769795 DOI: https://doi.org/10.3389/fphar.2017.00461

Cheon SS, Wei Q, Gurung A, Youn A, Bright T, Poon R, et al. Beta-catenin regulates wound size and mediates the effect of TGF-beta in cutaneous healing. FASEB J. 2006;20(6):692-701. https://doi.org/10.1096/fj.05-4759com PMid:16581977 DOI: https://doi.org/10.1096/fj.05-4759com

Liao XH, Nguyen H. Epidermal expression of Lgr6 is dependent on nerve endings and Schwann cells. Exp Dermatol. 2014;23(3):195-8. https://doi.org/10.1111/exd.12340 PMid:24499442 DOI: https://doi.org/10.1111/exd.12340

Whyte JL, Smith AA, Liu B, Manzano WR, Evans ND, Dhamdhere GR, et al. Augmenting endogenous Wnt signaling improves skin wound healing. PLoS One. 2013;8(10):e76883. https://doi.org/10.1371/journal.pone.0076883 PMid:24204695 DOI: https://doi.org/10.1371/journal.pone.0076883

Oyebode O, Kandala NB, Chilton PJ, Lilford RJ. Use of traditional medicine in middle-income countries: A WHO-SAGE study. Health Policy Plan. 2016;31(8):984-91. https://doi.org/10.1093/heapol/czw022 PMid:27033366 DOI: https://doi.org/10.1093/heapol/czw022

Ang AM, Enot MM, Baltazar GJ, Alinapon CV, Buncales EO, Barbosa GB. Antioxidant and cytotoxic activity of the leaf ethanolic extracts of Tithonia diversifolia and Gliricidia sepium from Bukidnon, Philippines. AJBLS. 2019;8(1):8-15. https://doi.org/10.5530/ajbls.2019.8.2 DOI: https://doi.org/10.5530/ajbls.2019.8.2

Molina-Botero IC, Montoya-Flores MD, Zavala-Escalante LM, Barahona-Rosales R, Arango J, Ku-Vera JC. Effects of long-term diet supplementation with Gliricidia sepium foliage mixed with Enterolobium cyclocarpum pods on enteric methane, apparent digestibility, and rumen microbial population in crossbred heifers1. J Anim Sci. 2019;97(4):1619-33. https://doi.org/10.1093/jas/skz067 PMid:30785622 DOI: https://doi.org/10.1093/jas/skz067

Aulanni’am A, Ora KM, Ariandini NA, Wuragil DK, Permata FS, Riawan W, et al. Wound healing properties of Gliricidia sepium leaves from Indonesia and the Philippines in rats (Rattus norvegicus). Vet World. 2021;14(3):820-4. https://doi.org/10.14202/vetworld.2021.820-824 PMid:33935433 DOI: https://doi.org/10.14202/vetworld.2021.820-824

Carandang RR, Buemio KC, Lopez A. The wound healing action of kakawati gel from Gliricidia sepium (Jacques) Steudel (Family Fabaceae). IJPTP. 2015;6(4):2642-9.

Kim SW, Roh J, Park CS. Immunohistochemistry for pathologists: Protocols, pitfalls, and tips. J Pathol Transl Med. 2016;50(6):411-8. https://doi.org/10.4132/jptm.2016.08.08 PMid:27809448 DOI: https://doi.org/10.4132/jptm.2016.08.08

Blanpain C, Fuchs E. Epidermal homeostasis: A balancing act of stem cells in the skin. Nat Rev Mol Cell Biol. 2009;10(3):207-17. https://doi.org/10.1038/nrm2636 PMid:19209183 DOI: https://doi.org/10.1038/nrm2636

Han G, Li F, Singh TP, Wolf P, Wang XJ. The pro-inflammatory role of TGFβ1: A paradox? Int J Biol Sci. 2012;8(2):228-35. https://doi.org/10.1006/excr.2000.493010.7150/ijbs.8.228 PMid:22253566 DOI: https://doi.org/10.7150/ijbs.8.228

Ferrari G, Cook BD, Terushkin V, Pintucci G, Mignatti P. Transforming growth factor-beta 1 (TGF-beta1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis. J Cell Physiol. 2009;219(2):449-58. https://doi.org/10.1002/jcp.21706 PMid:19180561 DOI: https://doi.org/10.1002/jcp.21706

Ghosh D, McGrail DJ, Dawson MR. TGF-β1 Pretreatment improves the function of mesenchymal stem cells in the wound bed. Front Dev Biol. 2017;5:28. https://doi.org/10.3389/fcell.2017.00028 PMid:28421182 DOI: https://doi.org/10.3389/fcell.2017.00028

Mori Y, Chen SJ, Varga J. Modulation of endogenous Smad expression in normal skin fibroblasts by transforming growth factor-beta. Exp Cell Res. 2000;258(2):374-83. https://doi.org/10.1006/excr.2000.4930 PMid:10896788 DOI: https://doi.org/10.1006/excr.2000.4930

Owens P, Han G, Li AG, Wang XJ. The role of Smads in skin development. J Invest Dermatol. 2008;128(4):783-90. https://doi.org/10.1038/sj.jid.5700969 PMid:18337711 DOI: https://doi.org/10.1038/sj.jid.5700969

Nakerakanti S, Trojanowska M. The role of TGF-β receptors in fibrosis. Open Rheumatol J. 2012;6:156-62. https://doi.org/10.2174/1874312901206010156 PMid:22802914 DOI: https://doi.org/10.2174/1874312901206010156

Li Y, Zhang J, Yue J, Gou X, Wu X. Epidermal stem cells in skin wound healing. Adv Wound Care (New Rochelle). 2017;6(9):297-307. https://doi.org/10.1089/wound.2017.0728 PMid:28894637 DOI: https://doi.org/10.1089/wound.2017.0728

Ku AT, Shaver TM, Rao AS, Howard JM, Rodriguez CN, Miao Q, et al. TCF7L1 promotes skin tumorigenesis independently of β-catenin through induction of LCN2. Elife. 2017;6:e23242. https://doi.org/10.7554/eLife.23242 PMid:28467300 DOI: https://doi.org/10.7554/eLife.23242

Kretzschmar K, Weber C, Driskell RR, Calonje E, Watt FM. Compartmentalized epidermal activation of β-catenin differentially affects lineage reprogramming and underlies tumor heterogeneity. Cell Rep. 2016;14(2):269-81. https://doi.org/10.1016/j.celrep.2015.12.04 PMid:26771241 DOI: https://doi.org/10.1016/j.celrep.2015.12.041

Romero N, Areche C, Cubides-Cárdenas J, Escobar N, García- Beltrán O, Simirgiotis MJ, et al. In vitro anthelmintic evaluation of Gliricidia sepium, Leucaena leucocephala, and Pithecellobium dulce: Fingerprint analysis of extracts by UHPLC-orbitrap mass spectrometry. Molecules. 2020;25(13):3002. https://doi.org/10.3390/molecules25133002 PMid:32630065 DOI: https://doi.org/10.3390/molecules25133002

Zhang Y, Guo L, Lu X, Cheng C, Sun S, Li W, et al. Characterization of Lgr6+ cells as an enriched population of hair cell progenitors compared to Lgr5+ cells for hair cell generation in the neonatal mouse cochlea. Front Mol Neurosci. 2018;11:147. https://doi.org/10.3389/fnmol.2018.00147 PMid:29867341 DOI: https://doi.org/10.3389/fnmol.2018.00147

Kim JY, Suh W. Stem cell therapy for dermal wound healing. Int J Stem Cells. 2010;3(1):29-31. https://doi.org/10.15283/ijsc.2010.3.1.29 PMid:24855538 DOI: https://doi.org/10.15283/ijsc.2010.3.1.29

Saputro ID, Rizaliyana S, Noverta DA. The effect of allogenic freeze-dried platelet-rich plasma in increasing the number of fibroblasts and neovascularization in wound healing. Ann Med Surg. 2022;73:103217. https://doi.org/10.1016/j.amsu.2021.103217 PMid:35079361 DOI: https://doi.org/10.1016/j.amsu.2021.103217

Husen SA, Syadzha MF, Setyawan MF, Pudjiastuti P, Ansori AN, Susilo RJ, et al. Evaluation of the combination of Sargassum duplicatum, Sargassum ilicifolium, Abelmoschus esculentus, and Garcinia mangostana extracts for open wound healing in diabetic mice. Syst Rev Pharm. 2020;11(9):888-92. https://doi.org/10.31838/srp.2020.9.129

Husen SA, Setyawan MF, Syadzha MF, Susilo RJ, Hayaza S, Ansori AN, et al. A novel therapeutic effects of Sargassum ilicifolium alginate and okra (Abelmoschus esculentus) pods extracts on open wound healing process in diabetic mice. Res J Pharm Technol. 2020;13(6):2764-70. https://doi.org/10.5958/0974-360X.2020.00491.6 DOI: https://doi.org/10.5958/0974-360X.2020.00491.6

Puspitaningrum MS, Rahmadhani D, Rizqianti Y, Ridwan RD, Ansori AN, Fadholly A, et al. Freeze-dried epigallocatechin- 3-gallate and stem-cells from human exfoliated deciduous-teeth scaffold as the biocompatible anti-relapse material post-orthodontic treatment: A review. Biochem Cell Arch. 2020;20:2935-42.

Fadholly A, Ansori AN, Proboningrat A, Kusala MK, Putri N, Pertiwi VR, et al. An investigation on the Euphoria longan (Lour.) Steud Seeds in Wound Healing in Rattus norvegicus. Indian Vet J. 2020;97(2):26-9.

Budi AC, Hamid IS, Legowo D. Tekelan leaves (Chromolaena odorata) infusion and 10% Povidone-iodine on incision wound healing process of mice (Mus musculus) infected with Staphylococcus aureus. World Vet J. 2021;11(1):60-5. https://doi.org/10.54203/scil.2021.wvj8 DOI: https://doi.org/10.54203/scil.2021.wvj8

Wulandari PA, Ilmi ZN, Husen SA, Winarni D, Alamsjah MA, Awang K, et al. Wound healing and antioxidant evaluations of alginate from Sargassum ilicifolium and Mangosteen rind combination extracts on diabetic mice model. Appl Sci. 2021;11(10):4651. https://doi.org/10.3390/app11104651 DOI: https://doi.org/10.3390/app11104651

Downloads

Published

2022-04-27

How to Cite

1.
Aulanni’am A, Raissa R, Riawan W, Wuragil DK, Permata FS, Beltran MAG. Epidermal Stem Cell in Wound Healing of Gliricidia sepium Leaves from Indonesia and the Philippines in Rats (Rattus norvegicus). Open Access Maced J Med Sci [Internet]. 2022 Apr. 27 [cited 2024 Nov. 21];10(A):1143-50. Available from: https://oamjms.eu/index.php/mjms/article/view/8637