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Cariniana domestica fruit peels present topical anti-inflammatory efficacy in a mouse model of skin inflammation

  • Gessica Brum Milani
  • Camila Camponogara
  • Mariana Piana
  • Cássia Regina Silva
  • Sara Marchesan OliveiraEmail author
Original Article
  • 23 Downloads

Abstract

To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (β-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1 mg/ear) and multiple (chronic; 0.4 mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and β-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and β-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1 mg/ear) fractions decreased the acute ear edema with maximum inhibition (Imax) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective Imax of 85 ± 6% (3%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). β-sitosterol (7.5 μg/ear), lupeol (10 μg/ear), and stigmasterol (5.7 μg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells’ infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1 mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE’s anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent.

Graphical abstract

Cariniana domestica, popularly known as jequitibá-roxo, presented topical anti-inflammatory activity in an acute and chronic irritant contact dermatitis croton oil-induced in mice. The crude extract (solutions and gel formulations) and different fractions obtained from fruit peels of C. domestica showed topical antiinflammatory activity on skin inflammation models with minimum adverse effects in preliminary toxicological studies (behavior and biochemical parameters). Moreover, the HPLC analysis revealed the presence of β-sitosterol, stigmasterol and lupeol, which also presented topical anti-inflammatory effect in the acute irritant contact dermatitis croton oil-induced. Our findings support the use of this species as a promising topical antiinflammatory agent.

Keywords

Jequitibá-roxo Dermatitis Stability Anti-inflammatory Steroids Adverse effects 

Abbreviations

CdE

Crude extract of C. domestica

MPO

Myeloperoxidase

NF-κB

Factor nuclear kappa B

ICD

Irritant contact dermatitis

ID50

Inhibitory dose 50%

Imax

Maximal inhibition

HTAB

Hexadecyltrimethylammoniumbromide

TMB

Tetramethylbenzidine

EDTA

Diaminoethanetetraacetic

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

s.c.

Subcutaneous

SEM

Standard error of the mean

TPA

12-O-Tetradecanoylphorbol-13-acetate

PKC

Protein kinase C

PLA2

Phospholipase A2

AP-1

Activating protein-1

Notes

Acknowledgments

We thank Professor Margareth Linde Athayde for donating the extract of C. domestica. We also thank the professor of the Program in Biological Sciences: Toxicological Biochemistry (Federal University of Santa Maria), Vera Morsh, for loaning equipment.

Author’s contribution

Participated in research design: G.B.M, C.C., C.R.S., S.M.O.

Conducted experiments: G.B.M, C.C., C.R.S., S.M.O.

Plant material and extractions, gel preparation, accelerated stability study, data analysis, writing, and discussion of these: M.P.

Performed data analysis: C.C., C.R.S., S.M.O.

Wrote or contributed to the writing of the manuscript: G.B.M, C.C., C.R.S., S.M.O.

All the authors reviewed the manuscript.

Funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior - CAPES/PROEX (process no. 23038.005848/2018-31; grant no. 0737/2018) (Brazil), and the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGS and the Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (grant no. 16/2551-0000281-9) and FAPERGS (Grant no. 17/2551-0001082-5). CC is recipient of fellowship from CAPES/PROEX (process no. 88882.182152/2018-01) and SMO is recipient of fellowship from CNPq (Grant no. 307220/2017-6). We also acknowledge fellowships from CNPq and CAPES.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution (approved by Institutional Committee for Animal Care and Use of the Federal University of Santa Maria, number process 9475221015/2015) and guidelines of Brazilian Council of Animal Experimentation—CONCEA—and of U.S. Public Health Service’s Policy on Humane Care and Use of Laboratory Animals—PHS Policy) were also followed.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact SciencesFederal University of Santa MariaSanta MariaBrazil
  2. 2.Phytochemical Research Laboratory, Graduate Program in Pharmaceutical Sciences, Center of Health SciencesFederal University of Santa MariaSanta MariaBrazil
  3. 3.Institute of Genetics and Biochemistry, Graduate Program in Genetics and BiochemistryFederal University of UberlandiaUberlandiaBrazil

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