Topical formulations containing Copaifera duckei Dwyer oleoresin improve cutaneous wound healing

Document Type : Original Research Article

Authors

1 Department of Veterinary Medicine, Universidade de Franca, Franca (SP), Brazil

2 Department of Veterinary Medicine, Instituto Federal do Sul de Minas Gerais, Muzambinho (MG), Brazil

3 Department of Veterinary Medicine, Universidade Federal de Goiás, Goiânia (GO), Brazil

4 Department of Veterinary Medicine, Universidade Estadual Paulista, Jaboticabal (SP), Brazil

5 Department of Sciences, Universidade de Franca, Franca (SP), Brazil

6 Department of Pharmacy, Universidade de São Paulo, Ribeirão Preto (SP), Brazil

Abstract

Objective: Evaluation of the healing and toxicological effects of Copaifera duckei Dwyer oleoresin (CDO).
Materials and Methods: Rodents with skin lesions were divided into nine groups, including daily treatments with 1, 3 and 10% CDO, collagenase, antibiotic ointment and control groups, for 14 days.
Results: Treatment with 10% CDO reduced skin edema and hyperplasia, demonstrating anti-inflammatory effect of the oil. Reduction in the wound area was observed, indicating the healing effect of CDO. Histopathological analysis showed increases in angiogenesis and re-epithelialization in animals treated with the highest concentration. On the other hand, no alterations in ulcerations, inflammatory infiltrate, hemorrhage, congestion, degeneration, percentage of collagen fibers, number of cells stained with anti-macrophage migration inhibitory factor, or density of area stained with anti-collagen I and III were found. Toxicogenetic analysis revealed no differences in micronucleus frequencies or in the ratio of polychromatic erythrocytes to total erythrocytes between treated and negative control, demonstrating the absence of genotoxicity and cytotoxicity, respectively. There was no difference in levels of liver enzymes among groups, indicating the absence of hepatotoxicity.
Conclusion: Formulations of CDO exerted beneficial effects on the stages of cutaneous wound healing and are promising options for the treatment of wounds.
 

Keywords


Ahmed AM, Hamid A, Soliman MFM. 2015.
Effect of topical Aloe vera on the process of
healing of full-thickness skin burn: a
histological and immunohistochemical
study. J Histol Histopathol, 2:1-9.
Bhatia N, Arunpreet S, Rohit S, Amandeep S,
Varinder S, Gurjeet S, Jaideep B, Ravi D,
Balwinder S. 2014. Evaluation of burn
wound healing potential of aqueous extract
of Morus alba based cream in rats. J
Phytopharm, 3:378-383.
Brito NMB, Simöes MJ Gomes PO, Pessoa AF,
Melo MCF. 1999. Microscopic aspects of
the cicatrization of treated open cutaneous
wounds with oil of copaiba in rats. Rev Para
Med, 13:12-7.
Carson FL, Hladik C. Histotechnology - a self
instructional text. 3. ed. Chicago: ASCP
Press, 2009. 400p.
Carvalho HO, Lima CS, Sanches AA, Silva JO,
Fernandes CP, Carvalho JCT. 2005. Study
of the in vitro release profile of
sesquiterpenes from a vaginal cream
containing Copaifera duckei Dwyer
(Fabaceae) oleoresin. J Appl Pharm Sci, 5:1-
6.
Castro-e-Silva O, Zucoloto S, Ramalho FS,
Ramalho LN, Reis JM, Bastos ÁA, Brito
MV. 2004. Antiproliferative activity of
Copaifera duckei oleoresin on liver
regeneration in rats. Phytother Res Int J
Devoted Pharmacol Toxicol Eval Nat Prod
Deriv, 18:92-94.
Emmerson E, Campbell L, Ashcroft GS,
Hardman MJ. 2009. Unique and synergistic
roles for 17β-estradiol and macrophage
migration inhibitory factor during cutaneous
wound closure are cell type specific.
Endocrinology, 150:2749-2757.
Flecknell PA, Richardson CA, Popovic A.
2007. Laboratory Animals. In: Tranquilli
WJ, Thurmon JC, Grimm KA. Lumb &
Jones Veterinary Anesthesia and Analgesia,
pp. 765-784, Iowa: Blackwell Publishing.
Furtado RA, Oliveira PF, Senedese JM, Ozelin
SD, Souza LDR, Leandro LF, Oliveira WL,
Silva JJM, Oliveira LC, Rogez H. 2018.
Assessment of genotoxic activity of
oleoresins and leaves extracts of six
copaifera species for prediction of potential
human risks. J Ethnopharmacol, 221:119-
125.
Gibot L, Galbraith T, Huot J, Auger FA. 2010.
A preexisting microvascular network
benefits in vivo revascularization of a
microvascularized tissue-engineered skin
substitute. Tissue Eng Part A, 16:3199-
3206.
Gilliver SC, Emmerson E, Bernhagen J,
Hardman MJ. 2011. MIF: A key player in
cutaneous biology and wound healing. Exp
Dermatol, 20:1-6.
Haagsma JA, Graetz N, Bolliger I, Naghavi M,
Higashi H, Mullany EC, Abera SF,
Abraham JP, Adofo K, Alsharif U. 2016.
The global burden of injury: incidence,
mortality, disabilityadjusted life years and
Gosuen Gonçalves Dias et al.
AJP, Vol. 11, No. 2, Mar-Apr 2021 132
time trends from the global burden of
disease study 2013. Inj Prev, 22: 3-18.
Leandro LM, Vargas FS, Barbosa PCS, Neves
JKO, Silva JÁ, Veiga-Junior VF. 2012.
Chemistry and biological activities of
terpenoids from copaiba (Copaifera spp.)
oleoresins. Mol Basel Switz, 17:3866-3889.
Lima CS, Medeiros BJL, Favacho HAS, Santos
KC, Oliveira BR, Taglialegna JC, Costa
EVM, Campos KJ, Carvalho JCT. 2011.
Pre-clinical validation of a vaginal cream
containing copaiba oil (Reproductive
toxicology study). Phytomedicine Int J
Phytother Phytopharm, 18:1013-1023.
Macri JA, Silva, SS, Miranda MM, Kawakami
NY, Madeira TB, Nixdorf SL, Acquaro
Junior VR, Ambrósio SR, Verri Junior WA,
Cecchini R, Conchon-Costa I, Arakawa NS,
Pavanelli WR. 2014. Immunomodulatory
and antioxidant properties of kaurenoic acid
on macrophages of BALB/c in vitro. Am J
Immunol, 10:184-188.
Martin LFT, Rocha EM, Garcia SB, Paula JS.
2013. Topical brazilian propolis improves
corneal wound healing and inflammation in
rats following alkali burns. BMC
Complement Altern Med, 13:1-7.
Moghadamtousi SZ, Rouhollahi E, Hajrezaie
M, Karimian H, Abdulla MA, Kadir HA.
2015. Annona muricata leaves accelerate
wound healing in rats via involvement of
Hsp70 and antioxidant defence. Int J Surg
Lond Engl, 18:110-117.
Noguchi A, Reis JMC, Dias CS, Epaminondas
WA, Azevedo PSR, Brito MVH. 2002.
Serum levels of aminotransferases,
bilirrubins and gamaglutamyltranspeptidase after copaiba oil
administration in rats. Acta Cir Bras,
17:130-134.
OECD-474 - Organization for Economic Cooperation and Development. Guideline for
the testing of chemicals - Mammalian
erythrocyte micronucleus test, 2016, p. 1-17.
Pistore M, Brustolin M, Rosset A, Zanella CA,
Cansian RL, Roman SS. 2014. Avaliação do
uso tópico do óleo
 essencial de Ruta graveolens L. (arruda) na
cicatrização de feridas em ratos. Revista
Perspectiva, 38:57-68.
Ramos AP, Pimentel LC. 2011. Effectiveness
of Aloe vera on the tissue repair and healing
process. Braz J Health, 2:40-48.
Rebolla A, Arisawa EALS, Barja PR, Posso
MBS, Carvalho CS. 2013. Effect of
Brassica oleracea in rats skin wound
healing. Acta Cir Bras, 28:664-669.
Reinke JM, Sorg H. 2012. Wound repair and
regeneration. Eur Surg Res Eur Chir Forsch
Rech Chir Eur, 49:35-43.
Riella KR, Marinho RR, Santos JS, PereiraFilho RN, Cardoso JC, Albuquerque-Junior
RLC, Thomazzi SM.
 2012. Anti-inflammatory and cicatrizing
activities of thymol, a monoterpene of the
essential oil from Lippia gracilis, in rodents.
J Ethnopharmacol, 143:56-663.
Santiago KB, Conti BJ, Andrade BFMT, Silva
JJM, Rogez HLG, Crevelin EJ, Moraes
LAB, Veneziani R, Ambrósio SR, Bastos
JK, Sforcin JM. 2015. Immunomodulatory
action of Copaifera spp oleoresins on
cytokine production by human monocytes.
Biomed Pharmacother, 70:12-18.
Santos GEC, Donnici CL, Camargos ERS,
Augusto de Rezende A, Andrade EHA,
Soares LAL, Farias LM, Carvalho RMA,
Almeida MG. 2013. Effects of Copaifera
duckei Dwyer oleoresin on the cell wall and
cell division of Bacillus cereus. J Med
Microbiol, 62:1032-1037.
Sérvio EMI, Araújo KS, Nascimento IRS,
Costa CLS, Mendes LMS, Maia Filho ALM,
Santos IMSP. 2011. Cicatrização de feridas
com a utilização do extrato de Chenopodium
ambrosioides (mastruz) e cobertura
secundária estéril de gaze em ratos.
ConScientiae Saúde, 10:441-448.
Sun G, Zhang X, Shen YI, Sebastian R,
Dickinson LE, Fox-Talbot K, Reinblatt M,
Steenbergen C, Harmon JW, Gerecht S.
2011. Dextran hydrogel scaffolds enhance
angiogenic responses and promote complete
skin regeneration during burn wound
healing. Proc Natl Acad Sci U. S. A.,
108:20976-20981.
Tillmann M, Felix A, Mueller EM, Felix S,
Alves G, Ramos T, Freitas R, Fernandes C,
Nobre M. 2014. Use of Triticum aestivum in
open wound healing: a clinical,
pathological, and tensiometric assessment in
the rabbit model. Arq Bras Med Vet Zootec,
66:1757-1761.
Veiga Junior VF, Rosas EC, Carvalho MV,
Henriques MGMO, Pinto AC. 2007.
Chemical composition and antiinflammatory activity of copaiba oils from
Copaifera cearensis Huber ex Ducke,
Copaifera reticulata Ducke and Copaifera
multijuga Hayne - a comparative study. J
Copaifera duckei Dwyer oleoresin improve cutaneous wound healing
AJP, Vol. 11, No. 2, Mar-Apr 2021 133
Ethnopharmacol, 112:248-254.
Vieira RC, Bombardiere E, Oliveira JJ, LinoJúnior RS, Brito LAB, Junqueira-Kipnis
AP. 2008. Influence of Copaifera
langsdorffii oil on the repair of a surgical
wound in the presence of foreign body. Pesq
Vet Bras, 28:358-366.
Zhao Y, Shimizu T, Nishihira J, Koyama Y,
Kushibiki T, Honda A, Watanabe H, Abe R,
Tabata Y, Shimizu H. 2005. Tissue
regeneration using macrophage migration
inhibitory factor-impregnated gelatin
microbeads in cutaneous wounds. Am J
Pathol, 167:1519-1529.