期刊论文详细信息
BMC Complementary and Alternative Medicine
Topical application of Acheflan on rat skin injury accelerates wound healing: a histopathological, immunohistochemical and biochemical study
Daniel Escorsim Machado1  Luiz Eurico Nasciutti1  Luiz Claudio Ferreira3  Jessica Alessandra-Perini3  Thais Angeli-Gamba2  Jamila Alessandra Perini3 
[1] Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil;Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Av. Manoel Caldeira de Alvarenga, 1203, Campo Grande, Rio de Janeiro, 23070-200, RJ, Brazil;Programa de Pós-Graduação em Saúde Pública e Meio Ambiente, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
关键词: VEGF;    Collagen;    Skin;    Wound healing;    Cordia verbenacea;    Acheflan®;   
Others  :  1216995
DOI  :  10.1186/s12906-015-0745-x
 received in 2014-11-18, accepted in 2015-06-24,  发布年份 2015
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【 摘 要 】

Background

Dermal wound healing involves a cascade of complex events including angiogenesis and extracellular matrix remodeling. Several groups have focused in the study of the skin wound healing activity of natural products. The phytomedicine Acheflan®, and its main active constituent is the oil from Cordia verbenacea which has known anti-inflammatory, analgesic and antimicrobial activities. To our knowledge, no investigation has evaluated the effect of Acheflan® in an experimental model of skin wound healing.

The present study has explored the wound healing property of Acheflan® and has compared it with topical effectiveness of collagenase and fibrinolysin by using Wistar rat cutaneous excision wound model.

Methods

Animals were divided into four groups: untreated animals are negative control (NC), wounds were treated topically every day with Collagenase ointment (TC), with Fibrinolysin ointment (TF) and with cream Acheflan (TAc). Skin samples were collected on zero, 8th and 15th days after wounding. The healing was assessed by hematoxylin-eosin (HE), picrosirius red, hydoxyproline content and immunohistochemical analysis of the vascular endothelial growth factor (VEGF) and matrix metalloprotease-9 (MMP-9). Statistical analysis was done by ANOVA and Student t-test (p < 0.05).

Results

The histological analysis HE of wound in the TAc group was more efficient because it was possible to observe the complete remodeling of the epidermis indicating the regression of lesions compared with the NC. The evaluation of picrosirius staining has demonstrated a significant increase of collagen distribution in the TC and TAc treatments compared with NC and TF groups. These results are corroborated with hydroxyproline content. Skin TC and TAc treated rats have showed an increase of VEGF and MMP-9 compared with NC and TF groups. All parameters were significant (P < 0.05).

Conclusion

The phytomedicine Acheflan® (oil of Cordia verbenacea) and TC possess higher therapeutic properties for wound healing compared with TF. These ointments seem to accelerate wound healing, probably due to their involvement with the increase of angiogenesis and dermal remodeling.

【 授权许可】

   
2015 Perini et al.

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【 参考文献 】
  • [1]Shaw TJ, Martin P et al.. Wound repair at a glance. J Cell Sci. 2009; 122:3209-3213.
  • [2]Singh A, Halder S, Menon GR, Chumber S, Misra MC, Sharma LK et al.. Meta-analysis of randomized controlled trials on hydrocolloid occlusive dressings versus conventional gauze in healing chronic wounds. Asian J Surg. 2004; 27:326-32.
  • [3]Singer AJ, Dagum AB. Current management of acute cutaneous wounds. N Engl J Med. 2008; 359:1037-1046.
  • [4]Calixto JB. Twenty-five years of research on medicinal plants in Latin America: a personal view. J Ethnopharmacol. 2005; 100:131-4.
  • [5]Balbani AP, Silva DH, Montovani JC. Patents of drugs extracted from Brazilian medicinal plants. Expert Opin Ther Pat. 2009; 19:461-73.
  • [6]Upadhyay A, Chattopadhyay P, Goyary D, Mazumder PM, Veer V. Topical application of Cleome viscosa increases the expression of basic fibroblast growth factor and type III collagen in rat cutaneous wound. Biomed Res Int. 2014; 2014:1-7.
  • [7]Samy RP, Kandasamy M, Gopalakrishnakone P, Stiles BG, Rowan EG, Becker D et al.. Wound healing activity and mechanisms of action of an antibacterial protein from the Venom of the Eastern Diamondback Rattlesnake (Crotalus adamanteus). Plos One. 2014; 9:1-16.
  • [8]Pang Y, Wang D, Fan Z, Chen X, Yu F, Hu X et al.. Blumea balsamifera—a phytochemical and pharmacological review. Molecules. 2014; 19:9453-9477.
  • [9]Zhang ZR, Li JH, Li S, Liu AL, Hoi PM, Tian HY et al.. In vivo angiogenesis screening and mechanism of action of novel tanshinone derivatives produced by one-pot combinatorial modification of natural tanshinone mixture from Salvia miltiorrhiza. Plos One. 2014; 9:1-15.
  • [10]Murthy S, Gautam MK, Goel S, Purohit V, Sharma H, Goel RK. Evaluation of in vivo wound healing activity of Bacopa monniera on different wound model in rats. Biomed Res Int. 2013; 2013:1-9.
  • [11]Nayak SB, Ramdath DD, Marshall JR, Isitor GN, Eversley M, Xue S et al.. Wound-healing activity of the skin of the common grape (Vitis Vinefera) variant, Cabernet Sauvignon. Phytother Res. 2010; 24:1151-7.
  • [12]Nayak SB, Sandiford S, Maxwell A. Evaluation of the wound-healing activity of ethanolic extract of Morinda citrifolia L. Leaf. Evid Based Complement Alternat Med. 2009; 6:351-6.
  • [13]Nayak SB, Rodrigues V, Maharaj S, Bhogadi VS. Wound healing activity of the fruit skin of Punica granatum. J Med Food. 2013; 16:857-61.
  • [14]Wong VW, Sorkin M, Glotzbach JP, Longaker MT, Gurtner GC. Surgical approaches to create murine models of human wound healing. J Biomed Biotechnol. 2011; 2011:1-8.
  • [15]Dorsett-Martin WA. Rat models of skin wound healing: a review. Wound Repair Regen. 2004; 12:591-599.
  • [16]Calixto JB. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res. 2000; 33:179-189.
  • [17]de Carvalho PMJR, Rodrigues RF, Sawaya AC, Marques MO, Shimizu MT. Chemical composition and antimicrobial activity of the essential oil of Cordiaverbenacea D.C. J Ethnopharmacol. 2004; 95:297-301.
  • [18]Chaves JS, Leal PC, Pianowisky L, Calixto JB. Pharmacokinetics and tissue distribution of the sesquiterpene alpha-humulene in mice. Planta Medica. 2008; 74:1678-83.
  • [19]Sertié JA, Woisky RG, Wiezel G, Rodrigues M. Pharmacological assay of Cordia verbenacea V: oral and topical anti inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract. Phytomedicine. 2005; 12:338-4.
  • [20]Medeiros R, Passos GF, Vitor CE, Koepp J, Mazzuco TL, Pianowiski LF, Campos MM, Calixto JB. Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw. British Journal of Pharmacology. 2007; 151:618-27.
  • [21]Matias EFF, Alves EF, Santos BS, Souza CES, Ferreira JVA, Lavor AKLS et al.. Biological activities and chemical characterization of Cordia verbenacea DC. as tool to validate the ethnobiological usage. Evid Based Complement Alternat Med. 2013; 2013:1-7.
  • [22]Pimentel SP, Barrella GE, Casarin RCV, Cirano FR. Protective effect of topical Cordia verbenacea in a rat periodontitis model: immune-inflammatory, antibacterial and morphometric assays. BMC Complement Altern Med. 2012; 12:224. BioMed Central Full Text
  • [23]Passos GF, Fernandes ES, da Cunha FM, Ferreira J, Pianowski LF, Campos MM et al.. Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. J Ethnopharmacol. 2007; 110:323-33.
  • [24]Fernandes ES, Passos GF, Medeiros R, da Cunha FM, Ferreira J, Campos MM et al.. Anti-inflammatory effects of compounds alpha-humulene and (−)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur J Pharmacol. 2007; 569:228-36.
  • [25]Morton JJP, Malone MH. Evaluation of vulnerary activity by an open wound procedure in rats. Arch Int Pharmacodyn. 1972; 196:117-9.
  • [26]Kim SW, Zhang HZ, Guo L, Kim JM, Kim MH. Amniotic mesenchymal stem cells enhance wound healing in diabetic NOD/SCID mice through high angiogenic and engraftment capabilities. Plos One. 2012; 7:1-11.
  • [27]Woessner JFJ. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961; 93:440-447.
  • [28]Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008; 453:314-321.
  • [29]Rizzi SC, Upton Z, Bott K, Dargaville TR. Recent advances in dermal wound healing: biomedical device approaches. Expert Rev Med Devices. 2010; 7:143-154.
  • [30]Peter FW, Li-Peuser H, Vogt PM, Muehlberger T, Homann HH, Steinau HU. The effect of wound ointments on tissue microcirculation and leucocyte behaviour. Clin Exp Dermatol. 2002; 27:51-55.
  • [31]Marazzi M, Stefani A, Chiaratti A, Ordanini MN, Falcone L, Rapisarda V. Effect of enzymatic debridement with collagenase on acute and chronic hard-to-heal wounds. Journal Wound Care. 2006; 15:222-227.
  • [32]Ostlie DJ, Juang D, Aquayo P, Pettiford-Cunningham JP, Erkmann EA, Rash DE et al.. Topical silver sulfadiazine vs collagenase ointment for the treatment of partial thickness burns in children: a prospective randomized trial. J Pediatr Surg. 2012; 47:1204-1207.
  • [33]Tallis A, Motley TA, Wunderlich RP, Dickerson JE, Waycaster C, Slade HB et al.. Clinical and economic assessment of diabetic foot ulcer debridement with collagenase: results of a randomized controlled study. Clin Ther. 2013; 35:1805-1820.
  • [34]Mekkes JR, Zeegelaar JE, Westerhof W. Quantitative and objective evaluation of wound debriding properties of collagenase and fibrinolysin/desoxyribonuclease in a necrotic ulcer animal model. Arch Dermatol Res 1998;290:152–7.
  • [35]Schwarz N. Enzymatic wound debridement with a combination of fibrinolysin and deoxyribonuclease. Fortschr Med. 1981; 99:978-80.
  • [36]Long KB, Burgwin CM, Huneke R, Artlett CM, Blankenhorn EP. Tight skin 2 mice exhibit delayed wound healing caused by increased elastic fibers in fibrotic skin. Adv Wound Care (New Rochelle). 2014; 3:573-581.
  • [37]El-Mesallamy HO, Diab MR, Hamdy NM, Dardir SM. Cell-based regenerative strategies for treatment of diabetic skin wounds, a comparative study between human umbilical cord blood-mononuclear cells and calves’ blood haemodialysate. Plos One. 2014; 9:1-10.
  • [38]Broughton G, Janis JE, Attinger CE. The basic science of wound healing. Plastic Reconstr Surg. 2006; 117(7 Suppl):12S-34S.
  • [39]Nayak SB, Ramdath DD, Marshall JR, Isitor G, Xue S, Shi J. Wound-healing properties of the oils of Vitis vinifera and Vaccinium macrocarpon. Phytother Res. 2011; 25:1201-8.
  • [40]Nayak SB, Nalabothu P, Sandiford S, Bhogadi V, Adogwa A. Evaluation of wound healing activity of Allamanda cathartica. L. and Laurus nobilis. L. extracts on rats. BMC Complement Altern Med. 2006; 6:12. BioMed Central Full Text
  • [41]Upadhyay A, Chattopadhyay P, Goyary D, Mazumder PM, Veer V. Ixora coccinea enhances cutaneous wound healing by upregulating the expression of collagen and basic fibroblast growth factor. ISRN Pharmacol. 2014; 2014:751824.
  • [42]Soyer T, Ayva S, Aliefendioğlu D, Aktuna Z, Aslan MK, Senyücel MF et al.. Effect of phototherapy on growth factor levels in neonatal rat skin. J Pediatr Surg. 2011; 46:2128-2131.
  • [43]Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997; 276:75-81.
  • [44]Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999; 341:738-746.
  • [45]Kim CH, Lee JH, Won JH, Cho MK. Early activation of matrix metalloproteinase-9 and vascular endothelial growth factor. J Korean Med Sci. 2011; 26:726-733.
  • [46]Volk SW, Iqbal SA, Bayat A. Interactions of the extracellular matrix and progenitor cell in cutaneous wound healing. Adv Wound Care. 2013; 2:261-272.
  • [47]Kurtz A, Oh SJ. Age related changes of the extracellular matrix and stem cell maintenance. Prev Med. 2012; 54:S50.
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