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Anti-inflammatory and antioxidant properties of Alternanthera brasiliana improve cutaneous wound healing in rats

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Abstract

Alternanthera brasiliana (L.) Kuntze is recognized for its healing properties; however, its therapeutic effects remain unclear. Therefore, our study aimed to elucidate the wound healing activities of A. brasiliana using in vitro and in vivo assays. In vitro assays were used to evaluate the antibacterial, anti-inflammatory, and antioxidant effects of A. brasiliana extract. For the in vivo study, two dorsal excisions were established in Wistar rats using a punch (1.5 cm in diameter), which were topically treated daily with 2% carbopol gel (Ctrl group) or 20% hydroalcoholic plant extract with 2% carbopol gel (A. brasiliana–Ab group). After the 2nd, 7th, 14th, and 21st days, inflammation, oxidative damage, antioxidants, angiogenesis, tissue formation, and re-epithelialization were evaluated. In vitro, Ab reduced nitric oxide, anion superoxide, and pro-inflammatory cytokine production. In vivo, Ab presented lower levels of inflammatory infiltrate, although increased levels of IL-1β and TGF-β1 were observed. The plant extract controlled oxidative damage by antioxidants, which favored angiogenesis, collagenesis, and wound re-epithelialization. Thus, the topical application of the hydroalcoholic extract of 20% A. brasiliana was distinguished by its important anti-inflammatory and antioxidant activities both in vivo and in vitro. The plant extract also stimulated angiogenesis and tissue formation, accelerating total re-epithelization, which is promising for wound healing.

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Data availability

We have availability of data and material.

Abbreviations

Ab:

Alternanthera brasiliana

ABTS:

2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)

CAT:

Catalase

Ctrl:

Control

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

EAC:

Ascitic Ehrlich carcinoma

FGF:

Fibroblast growth factor

FRAP:

Ferric ion-reducing antioxidant power

GSH:

Reduced glutathione

H2O2 :

Hydrogen peroxide

HO-Pro:

Hydroxyproline

IL-1β:

Interleukin 1 beta

IL-10:

Interleukin 10

IL-6:

Interleukin 6

KOH:

Potassium hydroxide

L929:

Fibroblast

LPS:

Lipopolysaccharide

MEAB:

Methanolic extract of Alternanthera brasiliana

MPO:

Myeloperoxidase

MRSA:

Methicillin-resistant Staphylococcus aureus

NAG:

N-acetylglycosaminidase

NO:

Nitric oxide

O2 . − :

Superoxide

PDGF:

Platelet-derived growth factor

RAW 264.7:

Macrophage RAW 264.7

SOD:

Superoxide dismutase

TGF-β1:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

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Acknowledgements

This work was financially supported by the Herminio Ometto Foundation. The authors also acknowledge all the support for the Undergraduate Students: Leandro Michelotto Baldin, Gabriela Fontana de Abreu Affonso, Amanda Pissinatti Canelli, Ariane Maria Zanesco, Alana Carolina Moscardi and Manuela Coloço Peres Samora, and the Professors: Maria Esmeria Corezola do Amaral, Maíra Felonato Mendes and Marcelo Augusto Marretto Esquisatto, and Editage (https://www.editage.com) for English language editing.

Funding

This study was funded by Herminio Ometto Foundation-FHO.

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Authors and Affiliations

  1. Graduate Program in Biomedical Sciences, University Center of Herminio Ometto Foundation–FHO, Dr. Maximiliano Baruto Ave, 500. Jardim Universitario, Araras, Sao Paulo, 13607-339, Brazil

    Rogério Marchete, Sarah Oliveira, Leonardo Bagne, Jennyffer Ione de Souza Silva, Ana Paula Valverde, Andrea Aparecida de Aro, Thainá Mikaela Bressam, Fernanda Oliveira de Gaspari de Gaspi, Gláucia Maria Tech dos Santos & Thiago Antônio Moretti Andrade

  2. Graduate Program of Pharmaceutical Sciences, Laboratory of Natural Products, University of Vila Velha–UVV, Comissario Jose Dantas de Melo Ave, 21. Boa Vista, Vila Velha, Espirito Santo, 29102‑920, Brazil

    Mariana Moreira Figueira & Marcio Fronza

  3. Graduate Program in Odontology, University Center of Herminio Ometto Foundation–FHO, Dr. Maximiliano Baruto Ave, 500. Jardim Universitario, Araras, SP, 13607-339, Brazil

    Vivian Fernandes Furletti de Goes

  4. Sao Leopoldo Mandic Faculty, Dona Renata Ave. Centro. 71, Araras, Sao Paulo, 13606-134, Brazil

    Fernanda Oliveira de Gaspari de Gaspi

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  1. Rogério Marchete
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  2. Sarah Oliveira
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  4. Jennyffer Ione de Souza Silva
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  6. Andrea Aparecida de Aro
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RM approved the version to be published, drafted the work or revised it critically for important intellectual content, and made substantial contributions to the analysis or interpretation of the data. SO approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis or interpretation of data. LB approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. JISS approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. APV approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. AAA approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. MMF approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. MF approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. TMB approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. VFFG approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. OGG approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data. GMTS approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the analysis, or interpretation of data, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved. TAMA approved the version to be published, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved, and made substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.

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Correspondence to Thiago Antônio Moretti Andrade.

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Marchete, R., Oliveira, S., Bagne, L. et al. Anti-inflammatory and antioxidant properties of Alternanthera brasiliana improve cutaneous wound healing in rats. Inflammopharmacol 29, 1443–1458 (2021). https://doi.org/10.1007/s10787-021-00862-3

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