Topical treatment with Copaifera langsdorffii oleoresin improves wound healing in rats
Keywords:
wound healing, Copaifera langsdorffii, phytotherapy, hydroxyproline, matrix metalloproteinasesAbstract
Copaifera langsdorffii oleoresin (copaiba) has been used in the Amazon as traditional wound healing remedy for centuries. Since its mechanisms of action remain unclear, we investigated its effects on excisional wounds in rats. Wounds were made on the dorsum of animals assigned to three groups: saline, control cream and 10% copaiba cream, and assessed on days 2, 7 and 14 post-wounding morphometrically, histologically and biochemically. Wound healing rate was faster in copaiba than in saline or cream groups. This was corroborated by matrix metalloproteinase (MMP)-2 activity which rose progressively throughout in copaiba group. MMP-9, a marker of inflammation, was not detectable at day 14 in copaiba group, but persisted in the other groups. Moreover, histology showed early population of copaiba-treated wounds by inflammatory cells, and by day 14 this group had less fibroblasts and more organized collagen. Further, copaiba group synthesized collagen faster than saline and cream groups, as evidenced by progressive increases in the amounts of hydroxyproline at days 7 and 14 (p < 0.012). These findings suggest that 10% copaiba oleoresin cream promotes wound healing in rats by regulating MMP-2 and MMP-9 activities, stimulating collagen synthesis and promoting tissue remodeling and reepithelialization.
References
Chalmers RL. The evidence for the role of transforming growth factor-beta in the formation of abnormal scarring. Int Wound J. 2011; 8:218-223.
. Schultz GS, Davidson JM, Kirsner RS, Bornstein P, Herman IM. Dynamic reciprocity in the wound microenvironment. Wound Repair Regen. 2011; 19:134-148.
. Percival SL, Slone W, Linton S, Okel T, Corum L, Thomas JG. The antimicrobial efficacy of a silver alginate dressing against a broad spectrum of clinically relevant wound isolates. Int Wound J. 2011; 8:237-143.
. Guo S, Dipietro LA. Factors Affecting Wound Healing. J Dent Res. 2010; 3:219-229.
. Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF. Impaired wound healing. Clin Dermatol. 2007; 25:19-25.
. Harding KG, Morris HL, Patel GK. Science, medicine and the future: Healing chronic wounds. BMJ. 2002; 324:160-163.
. Kokane DD, More RY, Kale,MB, Nehete MN, Mehendale PC, Gadgoli CH. Evaluation of wound healing activity of root of Mimosa pudica. J Ethnopharmacol. 2009; 124:311-315.
. Santos AO, Ueda-Nakamura T, Dias Filho BP, Veiga Junior VF, Nakamura CV. Copaiba Oil: An Alternative to Development of New Drugs against Leishmaniasis. Evid Based Complement Alternat Med. 2011; 2012:1-7.
. Masson-Meyers DS, Andrade TAM, Leite SN, Frade MAC. Cytotoxicity and wound healing properties of Copaifera langsdorffii oleoresin. Int J Nat Prod Sci. 2013; 3:10-20.
. Masson-Meyers DS, Enwemeka CS, Bumah VV, Andrade TAM, Cashin S, Frade MAC, Antimicrobial effects of Copaifera langsdorffii oleoresin in infected rat wounds. Int J Appl Microbiol Sci. 2013; 2:9-20.
. Nogueira Neto J, Lindose MJS, Coelho LF, Carvalho RAF, Rodrigues TGPM, Araújo AGP, Girão MJBC, Schor E. Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaifera langsdorffii). Acta Cir Bras 2011; 26(Suppl 2):20-24.
. Minatel DG, Frade, MAC, Franca S, Enwemeka CS. Phototherapy promotes healing of chronic diabetic leg ulcers that failed to respond to other therapies. Lasers Surg Med. 2009; 41:433-441.
. Kumar MS, Kirubanandan S, Sripriya R, Sehgal PK. Triphala promotes healing of infected full-thickness dermal wound. J Surg Res. 2008; 144:94-101.
. Shivhare Y, Singour PK, Patil UK, Pawar RS. Wound healing potential of methanolic extract of Trichosanthes dioica Roxb (fruits) in rats. J Ethnopharmacol. 2010; 127:614-619.
. Andrade TAM, Iyer A, Das PK, Foss NT, Garcia SB, Coutinho-Netto, J, Jordão-JR AA, Frade MAC. The inflammatory stimulus of a natural latex biomembrane improves healing in mice. Braz J Med Biol Res. 2011; 44:1036-1047.
. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996; 29:225-229.
. Nayak BS, Kanhai J, Milne DM, Pereira LP, Swanston WH. Experimental evaluation of ethanolic extract of Carapa guianensis L. leaf for its wound healing activity using three wound models. Evid Based Complement Alternat Med. 2009; 1-7.
. Adhirajan N, Shanmugasundaram N, Shanmuganathan S, Babu M. Collagen-based wound dressing for doxycycline delivery: in-vivo evaluation in an infected excisional wound model in rats. J Pharm Pharmacol. 2009; 61:1617-1623.
. Tang Z, Yang L, Zhang J, Xue R, Wang Y, Chen PC, Sung KLP. Coordinated expression of MMPs and TIMPs in rat knee intra-articular tissues after ACL injury. Connect Tissue Res. 2009; 50:315-322.
. Dachir S, Cohen M, Fishbeine E, Sahar R, Brandies R, Horwitz V, Kadar T. Characterization of acute and long-term sulphur mustard-induced skin injuries in hairless guinea-pigs using non-invasive methods. Skin Res Technol. 2010; 16:114-124.
. Ladwig GP, Robson MC, Liu R, Kuhn MA, Muir DF, Schultz GS. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers. Wound Repair Regen. 2002; 10:26-37.
. Rayment EA, Upton Z, Shooter GK. Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer. Br J Dermatol. 2008; 158:951-961.
. Hu X, Beeton C. Detection of functional matrix metalloproteinases by zymography. J Vis Exp. 2010; http://www.jove.com/index/ Details.stp?ID=2445.
. Paiva LAF, Cunha KMA, Santos FA, Gramosa NV, Silveira ER, Rao VSN. Investigation on the wound healing activity of oleoresin from Copaifera langsdorffii in rats. Phytother Res. 2002; 16:737-739.
. Liu Y, Min D, Bolton T, Nube V, Twigg SM, Yue DK, Mclennan SV. Increased matrix metalloproteinase-9 predicts poor wound healing in diabetic foot ulcers. Diabetes Care. 2009; 32:117-119.
. Gupta A, Upadhyay NK, Sawhney RC, Kumar R. A poly-herbal formulation accelerates normal and impaired diabetic wound healing. Wound Repair Regen. 2008; 16:784-790.
. Utz ER, Elster EA, Tadaki dk, Gage F, Perdue PW, Forsberg JA, Stojadinovic A, Hawksworth JS, Brown TS. Metalloproteinase expression is associated with traumatic wound failure. J Surg Res. 2010; 159:633-639.
. Kumar MS, Sripriya R, Raghavan HV, Seghal PK. Wound healing potential of Cassia fistula on infected albino rat model. J Surg Res. 2006; 131:283-289.
. Reiss MJ, Han YP, Garcia E, Goldberg M, Yu H, Garner WL. Matrix metalloproteinase-9 delays wound healing in a murine wound model. Surgery. 2010; 147:295-302.
. Ramos MFS: Development of microcapsules containing the volatile fraction of copaiba by spray-drying: study of stability and pharmacological evaluation. PhD thesis. University of Sao Paulo, School of Pharmaceutical Sciences of Ribeirao Preto; 2006.
. Deshmukh PT, Fernandes J, Atul A, Toppo E. Wound healing activity of Calotropis gigantea root bark in rats. J Ethnopharmacol. 2009; 125:178-181.
. Sousa JPB, Brancalion APS, Souza AB, Souza AB, Turatti ICC, Ambrosio SR, Furtado NAJC, Lopes NP, Bastos JK. Validation of a gas chromatographic method to quantify sesquiterpenes in copaiba oils. J Pharm Biomed Anal. 2010; 54:653-659.
. Sasidharan S, Nilawatyi R, Xavier R, Latha LY, Amaka R. Wound healing potential of Elaeis guineensis Jacq leaves in an infected albino rat model. Molecules. 2010; 15:3186-3199.
