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Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model.

Methods

Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5 μg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas.

Results

TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P<0.01) and in vitro (90% vs. 65% reduction in wound area, P<0.01). Moreover, topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4, HMGCoA, SPT, filaggrin, loricrin and involucrin (P<0.05 vs. vehicle-treated controls) on day 3 after wounding. Likewise, TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 (33.06±2.09 g/(m2·h) vs. 24.60±2.04 g/(m2·h), P<0.01).

Conclusions

Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function, leading to acceleration of acute cutaneous WH. Topical products containing TASE could be used to manage acute cutaneous WH.

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Acknowledgment

Authors are grateful to Dr. Lucia Gonzalez-Lopez from the Pathology Service (Hospital General Universitario de Ciudad Real, Ciudad Real, Spain) for her expert advice and kind support. We also thank David Gallego-Molinero, Amelia Gonzalez-Lopez and Clara Villar-Rodriguez for their technical support (Translational Research Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain).

Author information

Authors and Affiliations

  1. Dermatology Service, Hospital General Universitario de Ciudad Real, Ciudad Real, 13004, Spain

    Juan Luis Santiago

  2. Translational Research Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, 13004, Spain

    Juan Luis Santiago, Eva Maria Galan-Moya, Jose Ramon Muñoz-Rodriguez, Miguel Angel de la Cruz-Morcillo, Francisco Javier Redondo-Calvo & Jose Manuel Perez-Ortiz

  3. Translational Oncology Laboratory, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Albacete, 02008, Spain

    Eva Maria Galan-Moya

  4. Instituto de Tecnología Química y Medioambiental, Universidad de Castilla-La Mancha, Ciudad Real, 13004, Spain

    Ignacio Gracia-Fernandez

  5. Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, CA, 94121, USA

    Peter M. Elias & Mao-Qiang Man

  6. Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China

    Mao-Qiang Man

Authors
  1. Juan Luis Santiago
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  2. Eva Maria Galan-Moya
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  4. Miguel Angel de la Cruz-Morcillo
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  8. Jose Manuel Perez-Ortiz
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  9. Mao-Qiang Man
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Contributions

JLS, EMG-M, MQM and JMP-O designed the experiments, conducted data analyses, and wrote the manuscript; PME critically reviewed the manuscript; JLS, FJR-C and JMP-O performed animal experiments; EMG-M did the in vitro studies; JRM-R and MAC-M performed molecular experiments and analyzed data; IG-F prepared and provided the lyophilized Allium sativum extract for both in vivo and in vitro studies.

Corresponding authors

Correspondence to Jose Manuel Perez-Ortiz or Mao-Qiang Man.

Ethics declarations

All authors, except IG-F, have no conflicts of interest. IG-F is part of the patent authors [WO 2008/102036 A1. Method for obtaining a freeze-dried, stable extract from plants of the Allium genus] from which the lyophilized Allium sativum extract was obtained in a standardized way. This content is solely the responsibility of the authors and does not necessarily represent the official views of either the funding agencies or the US Department of Veterans Affairs.

Additional information

Supported by the European Commission/FSE Funds to EMG-M, the European Regional Development Fund (JRM-R and JMP-O, Castilla-La Mancha FEDER 2014-20 PO), the Government of Castilla-La Mancha (MAC-M, Ref. II-2016-06), and the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health (PEM & MQM, AR061106), with additional resources provided by The Veterans Affairs Medical Center, San Francisco, CA, USA

Electronic supplementary material

11655_2020_3086_MOESM1_ESM.pdf

Appendix 1. Composition of Organic and Inorganic Compounds of Lyophilized Allium sativum Extract from Las Pedroñeras (Ciudad Real, Spain) under Optimized Conditions (WO 2008/102036 A1)

Appendix 2. Primers for qPCR

Appendix 3. Experimental Procedures and Results

Appendix 4. Thiosulfinate-Enriched Allium sativum Extract Accelerates Wound Healing

11655_2020_3086_MOESM5_ESM.pdf

Appendix 5. Expression Levels of mRNAs Following 8-Day Treatments with Thiosulfinate-Enriched Allium sativum Extract or Vehicle

Appendix 6. Expression of Filaggrin Following Treatments with Thiosulfinate-Enriched Allium Sativum Extract or Vehicle

Appendix 7. Expression of Involucrin Following Treatments with Thiosulfinate-Enriched Allium Sativum Extract or Vehicle

Appendix 8. Expression of Loricrin Following Treatments with Thiosulfinate-Enriched Allium Sativum Extract or Vehicle

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Santiago, J.L., Galan-Moya, E.M., Muñoz-Rodriguez, J.R. et al. Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model. Chin. J. Integr. Med. 26, 812–818 (2020). https://doi.org/10.1007/s11655-020-3086-7

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  • DOI: https://doi.org/10.1007/s11655-020-3086-7

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