EFFECT OF CRUDE EXTRACT AND PHYTOSTEROL FRACTION OF FUMARIA OFFICINALIS IN INDUCED HYPERTROPHIC SCAR OF RABBITS

  • HANAN S NOORI Department of Pharmacology and Therapeutics, College of Medicine, AL‑Nahrain University, Iraq.
  • AHMED ABU‑RAGHIF Department of Pharmacology and Therapeutics, College of Medicine, AL‑Nahrain University, Iraq.

Abstract

Objective: The present study aimed to evaluate the role of crude extract and phytosterol fraction of Fumaria officinalis in experimentally induced hypertrophic scar in rabbits.


Methods: Surgical wounds were performed on day 1 with an 8‑mm biopsy punch four wounds were created on the ventral surface of the rabbit ear (in vivo) down to cartilage. Triamcinolone acetonide (TAC), crude and phytosterol extracts of F. officinalis L. are administered topically to established scars on day 31. The outcome measures included study of histopathology of skin sections, transforming growth factor beta‑1 (TGF‑β1), level, and collagen three alpha1 in skin tissue.


Results: In comparison with the induced hypertrophic scar, all treatment produced a significant reduction in scores of TGFβ1, collagen III, inflammation, and measurement of SEI (p ≤ 0.01). The most significant reduction in inflammation and thickness observed in TAC and extract of crude F. officinalis L. Only crude F. officinalis L. decrease fibroblast counts in comparison to induced hypertrophic scar group and other group (p ≤ 0.05). No statistically significant differences were found between the treatment groups in terms of TGF β1and collagen III.


Conclusion: Topical crude extract of F. officinalis L. was more effective in the treatment of induced hypertrophic scar as compared with phytosterol of F. officinalis L. and comparable to the effectiveness of topical TAC.

Keywords: Hypertrophic scar, Rabbit ear model, SEI, Collagen I.

References

1. Lee HJ, Jang YJ. Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids. Int J Mol Sci 2018;19:E711.
2. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies. Mol Med 2011;17:113 25.
3. Wolfram D, Tzankov A, Pülzl P, Piza Katzer H. Hypertrophic scars and keloids a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg 2009;35:171 81.
4. O’Leary R, Wood EJ, Guillou PJ. Pathological scarring: Strategic interventions. Eur J Surg 2002;168:523 34.
5. Krakowski AC, Totri CR, Donelan MB, Shumaker PR. Scar management in the pediatric and adolescent populations. Pediatrics 2016;137:e20142065.
6. Bombaro KM, Engrav LH, Carrougher GJ, Wiechman SA, Faucher L, Costa BA, et al. What is the prevalence of hypertrophic scarring following burns? Burns 2003;29:299 302.
7. Ren HT, Hu H, Li Y, Jiang HF, Hu XL, Han CM, et al. Endostatin inhibits hypertrophic scarring in a rabbit ear model. J Zhejiang Univ Sci B 2013;14:224 30.
8. Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: A review. Plast Reconstr Surg 1999;104:1435 58.
9. Dakhil AS. Association of serum concentrations of proinflammatory cytokines and hematological parameters in rheumatoid arthritis patients. J Pharm Sci Res 2017;9:1966 74.
10. Andrews JP, Marttala J, Macarak E, Rosenbloom J, Uitto J. Keloids: The paradigm of skin fibrosis pathomechanisms and treatment. Matrix Biol 2016;51:37 46.
11. Klass BR, Grobbelaar AO, Rolfe KJ. Transforming growth factor beta1 signalling, wound healing and repair: A multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J 2009;85:9 14.
12. Xie JL, Qi SH, Pan S, Xu YB, Li TZ, Liu XS, et al. Expression of smad protein by normal skin fibroblasts and hypertrophic scar fibroblasts in response to transforming growth factor beta1. Dermatol Surg 2008;34:1216 24.
13. Wang R, Ghahary A, Shen Q, Scott PG, Roy K, Tredget EE, et al. Hypertrophic scar tissues and fibroblasts produce more transforming growth factor beta1 mRNA and protein than normal skin and cells. Wound Repair Regen 2000;8:128 37.
14. Mezher MN, Dakhil AS, Jawad DH. Role of epstein barr virus (EBV) in human females with breast cancer. J Pharm Sci Res 2017;9:1173 7.
15. Thomas F. PDR for Herbal Medicines. Montvale, New Jersey: Medical Economics Company; 2000. p. 322.
16. Sturm S, Strasser EM, Stuppner H. Quantification of Fumaria officinalis isoquinoline alkaloids by nonaqueous capillary electrophoresis electrospray ion trap mass spectrometry. J Chromatogr A 2006;1112:331 8.
17. Dermaderosian A, Beutler JA. The Review of Natural Products. 4th ed. Baltimore, MD: Lippincott Williams and Wilkins, Wolters Kluwer Health Inc.; 2005. p. 458 60.
18. Molokhova LG, Suslina ML, Datskovskii SB, Figurkin BA. Anti inflammatory effect of fumitory alkaloids. Tr Permsk God Med Inst 1973;118:26 8.
19. Dakhil AS. Biosynthesis of silver nanoparticle (AgNPs) using Lactobacillus and their effects on oxidative stress biomarkers in rats. J King Saud Univ Sci 2017;29:462 7.
20. Grattan BJ Jr. Plant sterols as anticancer nutrients: Evidence for their role in breast cancer. Nutrients 2013;5:359 87.
21. Awad AB, Williams H, Fink CS. Phytosterols reduce in vitro metastatic ability of MDA MB 231 human breast cancer cells. Nutr Cancer 2001;40:157 64.
22. Harborne JB. Phytochemical Methods, a Guide to Modern Techniques of Plant Analysis. 1st ed. London, New York: Chapman and Hall; 1979. p. 278.
23. Dakhil AS, Al Hajjiah NN, Shlash RF. Identification of factor viii gene mutations in patients with haemophilia A. Int J Res Pharm Sci 2018;9:274 28.
24. Singh MP, Nagori BP, Shaw NR, Tiwari M, Jhanwar B. Formulation development and evaluation of topical gel formulations using different gelling agents and its comparison with marketed gel formulation. Int J Pharm Erudition 2013;3:1 10.
25. Attia MA, El Gibaly I, Shaltout SE, Fetih GN. Transbuccal permeation, anti inflammatory activity and clinical efficacy of piroxicam formulated in different gels. Int J Pharm 2004;276:11 28.
26. Yagmur C, Guneren E, Kefeli M, Ogawa R. The effect of surgical denervation on prevention of excessive dermal scarring: A study on rabbit ear hypertrophic scar model. J Plast Reconstr Aesthet Surg 2011;64:1359 65.
27. Weiss AT, Delcour NM, Meyer A, Klopfleisch R. Efficient and cost effective extraction of genomic DNA from formalin fixed and paraffin embedded tissues. Vet Pathol 2011;48:834 8.
28. Anderson G, Gordon KC. Tissue processing, microtomy, andparaffin sections. In: Bancroft D, Stevens A, editrors. Theory and Practice of Histological Techniques. New York: Churchill Livingstone; 1996. p. 47 67.
29. Saulis AS, Mogford JH, Mustoe TA. Effect of mederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002;110:177 83.
30. Longo RE, Sao Dimas J. Effects of Chamomilla recutita (L) on oral wound healing in rats. Cir Bucal 2002;16:e716 21.
31. Gál P, Vasilenko T, Kostelníková M, Jakubco J, Kovác I, Sabol F, et al. Open wound healing in vivo: Monitoring binding and presence of adhesion/growth regulatory galectins in rat skin during the course of complete re epithelialization. Acta Histochem Cytochem 2011;44:191 9.
32. Prignano F, Campolmi P, Bonan P, Ricceri F, Cannarozzo G, Troiano M, et al. Fractional CO2 laser: A novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair. Dermatol Ther 2009;22 Suppl 1:S8 15.
33. Daniel WW. 7.10, determining sample size to control Type II errors. In: Biostatistics a Foundation for Analysis in the Health Sciences. 9th ed. Ch. 7. Hoboken, New Jersey: Wiley; 2009. p. 278.
34. Mehta M, Branford OA, Rolfe KJ. The evidence for natural therapeutics as potential anti scarring agents in burn related scarring. Burns Trauma 2016;4:15.
35. Penn JW, Grobbelaar AO, Rolfe KJ. The role of the TGF ? family in wound healing, burns and scarring: A review. Int J Burns Trauma 2012;2:18 28.
36. Ko JH, Kim PS, Zhao Y, Hong SJ, Mustoe TA. HMG coA reductase inhibitors (statins) reduce hypertrophic scar formation in a rabbit ear wounding model. Plast Reconstr Surg 2012;129:252e 61e.
37. Tang M, Wang W, Cheng L, Jin R, Zhang L, Bian W, et al. The inhibitory effects of 20(R) ginsenoside rg3 on the proliferation, angiogenesis, and collagen synthesis of hypertrophic scar derived fibroblasts in vitro. Iran J Basic Med Sci 2018;21:309 17.
38. Lu L, Saulis AS, Liu WR, Roy NK, Chao JD, Ledbetter S, et al. The temporal effects of anti TGF beta1, 2, and 3 monoclonal antibody on wound healing and hypertrophic scar formation. J Am Coll Surg 2005;201:391 7.
39. Wick G, Grundtman C, Mayerl C, Wimpissinger TF, Feichtinger J, Zelger B, et al. The immunology of fibrosis. Annu Rev Immunol 2013;31:107 35.
40. Manna MJ, Abu Raghif A, Abbood MS. Effect of captopril on inflammatory biomarkers, oxidative stress parameters and histological outcome in experimental induced colitis. J Pharm Sci Res 2017;9:1629 36.
41. Ide M, Jinnin M, Tomizawa Y, Wang Z, Kajihara I, Fukushima S, et al. Transforming growth factor ? inhibitor repsox down regulates collagen expression of scleroderma dermal fibroblasts and prevents bleomycin induced mice skin fibrosis. Exp Dermatol 2017;26:1139 43.
42. Klingberg F, Hinz B, White ES. The myofibroblast matrix: Implications for tissue repair and fibrosis. J Pathol 2013;229:298 309.
43. Kim SY, Nam SM, Park ES, Kim YB. Differences in hypertrophic scar fibroblasts according to scar severity: Expression of transforming growth factor ?1 at the mRNA and protein levels. Arch Aesthetic Plast Surg 2015;21:116 20.
44. Sari E, Bakar B, Dincel GC, Budak Yildiran FA. Effects of DMSO on a rabbit ear hypertrophic scar model: A controlled randomized experimental study. J Plast Reconstr Aesthet Surg 2017;70:509 17.
45. Jurjus A, Atiyeh BS, Abdallah IM, Jurjus RA, Hayek SN, Jaoude MA, et al. Pharmacological modulation of wound healing in experimental burns. Burns 2007;33:892 907.
46. Roa Engel CA, Straathof AJ, Zijlmans TW, van Gulik WM, van der Wielen LA. Fumaric acid production by fermentation. Appl Microbiol Biotechnol 2008;78:379 89.
47. Ivanov I, Vrancheva R, Marchev A, Petkova NT, Aneva IY, Denev PP, et al. Antioxidant activities and phenolic compounds in Bulgarian fumaria species. Int J Curr Microbiol Appl Sci 2014;3:296 306.
48. Al Hajjiah NN, Almkhadree MA. The effect of maternal anemia on the anthropometric measurements in full term neonates. Asian J Pharm Clin Res 2018;11:3680 1.
49. Al Hajjiah NN, Al Shamsi MM, Al Shami MM. The rate of parental refusal lumbar puncture in the maternity and children teaching hospital in Diwaniyah, Iraq. J Pharm Sci Res 2018;10:2680 1.
50. Oliveira GV, Hawkins HK, Chinkes D, Burke A, Tavares AL, Ramos e Silva M, et al. Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and laser confocal microscopy: Type I and III collagens. Int Wound J 2009;6:445 52.
51. Uzun H, Bitik O, Hekimo?lu R, Atilla P, Kayikçio?lu AU. Angiotensin converting enzyme inhibitor enalapril reduces formation of hypertrophic scars in a rabbit ear wounding model. Plast Reconstr Surg 2013;132:361e 71e.
52. Rizvi W, Fayazuddin M, Singh O, Syed SN, Moin S, Akhtar K, et al. Anti inflammatory effect of Fumaria parviflora leaves based on TNF ?, IL 1, IL 6 and antioxidant potential. Avicenna J Phytomed 2017;7:37 45.
53. Pandey G, Kumar GR, Gupta SS, Ojha SK, Rao CV. Wound repair and anti inflammatory potential of Fumaria indica in excision wound induced rats. Br J Pharm Res 2014;4:257 66.
54. Pessoa ES, Melhado RM, Theodoro LH, Garcia VG. A histologic assessment of the influence of low intensity laser therapy on wound healing in steroid treated animals. Photomed Laser Surg 2004;22:199 204.
55. Shakya A, Chatterjee SS, Kumar V. Holistic psychopharmacology of Fumaria indica (Fumitory). Chin Med 2012;3:182 99.
56. Çal?skan E, Gams?zkan M, Aç?kgöz G, Durmu? M, Toklu S, Do?rul A, et al. Intralesional treatments for hypertrophic scars: Comparison among corticosteroid, 5 fluorouracil and botulinum toxin in rabbit ear hypertrophic scar model. Eur Rev Med Pharmacol Sci 2016;20:1603 8.
57. Capistrano IR, Wouters A, Lardon F, Gravekamp C, Apers S, Pieters L, et al. In vitro and in vivo investigations on the antitumour activity of Chelidonium majus. Phytomedicine 2015;22:1279 87.
Statistics
29 Views | 278 Downloads
How to Cite
S NOORI, H., and A. ABU‑RAGHIF. “EFFECT OF CRUDE EXTRACT AND PHYTOSTEROL FRACTION OF FUMARIA OFFICINALIS IN INDUCED HYPERTROPHIC SCAR OF RABBITS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 2, Jan. 2019, pp. 484-91, https://innovareacademics.in/journals/index.php/ajpcr/article/view/30448.
Section
Original Article(s)