Effectiveness of a Crocus sativus Extract on Burn Wounds in Rats

Abstract

Crocus sativus is a spice with various pharmacological properties. Crocin, picrocrocin, and safranal are the main compositions of saffron that have recently been considered in the therapy of many diseases. High-performance liquid chromatography analysis revealed presence of these compounds in our saffron extract. This study was carried out to evaluate the effect of saffron on burn wound healing at an in vivo model. Saffron was topically applied on burn wounds in rats; the percentage of wound closure, wound contraction, and the levels of main cytokines and growth factors were measured. The saffron extract was also applied to evaluate the proliferation and migration of human dermal fibroblast (HDF) cells using in vitro scratch assay and resulted in active proliferation and migration of the HDF cells in a dose-dependent manner. A clear enhanced healing was observed in the saffron-treated wounds compared to the silver sulfadiazine and negative control groups. Decreased expression of interleukin-1β and transforming growth factor-β1 (TGF-β1) during the inflammatory phase demonstrated the role of saffron in promoting wound healing. In addition, enhanced TGF-β1 expression during the proliferative phase and basic fibroblast growth factor during the remodeling phase represented regenerative and anti-scarring role of saffron, respectively. Our histological and biochemical findings also confirmed that saffron significantly stimulated burn wound healing by modulating healing phases. Therefore, saffron can be an optimal option in promoting skin repair and regeneration. Application of this herbal medicinal drug should be encouraged because of its availability and negligible side effects.

Key words

Crocus sativus - Iridaceae - interleukin-1β - wound healing - scratch assay

• References

• 1 Bahramsoltani R, Farzaei MH, Rahimi R. Medicinal plants and their natural components as future drugs for the treatment of burn wounds: an integrative review. Arch Dermatol Res 2014; 306: 601-617
• 2 Porter C, Hurren NM, Herndon DN, Børsheim E. Whole body and skeletal muscle protein turnover in recovery from burns. Int J Burns Trauma 2013; 3: 9
• 3 Oryan A, Alemzadeh E, Moshiri A. Burn wound healing: present concepts, treatment strategies and future directions. J Wound Care 2017; 26: 5-19
• 4 Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, Chan RK, Christy RJ, Chung KK. Burn wound healing and treatment: review and advancements. Crit Care 2015; 19: 243
• 5 Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev 2006; 19: 403-434
• 6 Alemdaroğlu C, Değim Z, Çelebi N, Zor F, Öztürk S, Erdoğan D. An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor. Burns 2006; 32: 319-327
• 7 Du J, Liu L, Lay F, Wang Q, Dou C, Zhang X, Hosseini S, Simon A, Rees D, Ahmed A. Combination of HIF-1 [alpha] gene transfection and HIF-1-activated bone marrow-derived angiogenic cell infusion improves burn wound healing in aged mice. Gene Ther 2013; 20: 1070
• 8 Dai T, Huang YY, Sharma SS, Hashmi JT, Kurup DB, Hamblin MR. Topical antimicrobials for burn wound infections. Recent Pat Antiinfect Drug Discov 2010; 5: 124-151
• 9 Atiyeh BS, Costagliola M, Hayek SN, Dibo SA. Effect of silver on burn wound infection control and healing: review of the literature. Burns 2007; 33: 139-148
• 10 Caballero-Ortega H, Pereda-Miranda R, Abdullaev FI. HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources. Food Chem 2007; 100: 1126-1131
• 11 Kosar M, Demirci B, Goger F, Kara I, Baser K. Volatile composition, antioxidant activity and antioxidant components in saffron cultivated in Turkey. Int J Food Prop 2017; 20: S746-S754
• 12 Boskabady MH, Farkhondeh T. Antiinflammatory, antioxidant, and immunomodulatory effects of Crocus sativus L. and its main constituents. Phytother Res 2016; 30: 1072-1094
• 13 Boskabady MH, Tabatabaee A, Byrami G. The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs. Phytomedicine 2012; 19: 904-911
• 14 Gholamnezhad Z, Koushyar H, Byrami G, Boskabady MH. The extract of Crocus sativus and its constituent safranal, affect serum levels of endothelin and total protein in sensitized guinea pigs. Iran J Basic Med Sci 2013; 16: 1022-1026
• 15 Samarghandian S, Shoshtari ME, Sargolzaei J, Hossinimoghadam H, Farahzad JA. Anti-tumor activity of safranal against neuroblastoma cells. Pharmacogn Mag 2014; 10: S419
• 16 Hassani FV, Naseri V, Razavi BM, Mehri S, Abnous K, Hosseinzadeh H. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. DARU J Pharm Sci 2014; 22: 16
• 17 Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. The effect of Crocus sativus extract on human lymphocytesʼ cytokines and T helper 2/T helper 1 balance. J Med Food 2011; 14: 1538-1545
• 18 Byrami G, Boskabady MH, Jalali S, Farkhondeh T. The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized guinea-pigs. J Ethnopharmacol 2013; 147: 530-535
• 19 Feyzi R, Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei SA. The effect of safranal on Th1/Th2 cytokine balance. Iran J Immunol 2016; 13: 263-273
• 20 Verjee S, Garo E, Pelaez S, Fertig O, Hamburger M, Butterweck V. Saffron flower extract promotes scratch wound closure of keratinocytes and enhances VEGF production. Planta Med 2017; 83: 1176-1183
• 21 Assimopoulou A, Sinakos Z, Papageorgiou V. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res 2005; 19: 997-1000
• 22 Dar RA, Brahman PK, Khurana N, Wagay JA, Lone ZA, Ganaie MA, Pitre KS. Evaluation of antioxidant activity of crocin, podophyllotoxin and kaempferol by chemical, biochemical and electrochemical assays. Arab J Chem 2013; 10: S1119-S1128
• 23 Kanakis C, Tarantilis P, Pappas C, Bariyanga J, Tajmir-Riahi H, Polissiou M. An overview of structural features of DNA and RNA complexes with saffron compounds: models and antioxidant activity. J Photochem Photobiol B 2009; 95: 204-212
• 24 Nagane N, Bhagwat V, Subramanium M. Increased free radical activity in burns. Indian J Med Sci 2003; 57: 7-11
• 25 Al-Jawad F, Sahib A, Al-Kaisy A. Role of antioxidants in the treatment of burn lesions. Ann Burns Fire Disasters 2008; 21: 186
• 26 Khorasani G, Hosseinimehr SJ, Zamani P, Ghasemi M, Ahmadi A. The effect of saffron (Crocus sativus) extract for healing of second-degree burn wounds in rats. Keio J Med 2008; 57: 190-195
• 27 Mehrabi S, Shokpoor M, Jamilian M, Sakhi H. Evaluation of the effect of saffron 20 % cream on the level of infection and episiotomy dehiscence. AMUJ 2015; 18: 75-84
• 28 Ipaktchi K, Mattar A, Niederbichler AD, Hoesel LM, Vollmannshauser S, Hemmila MR, Su GL, Remick DG, Wang SC, Arbabi S. Attenuating burn wound inflammatory signaling reduces systemic inflammation and acute lung injury. J Immunol 2006; 177: 8065-8071
• 29 Correa SG, Maccioni M, Rivero VE, Iribarren P, Sotomayor CE, Riera CM. Cytokines and the immune-neuroendocrine network: what did we learn from infection and autoimmunity?. Cytokine Growth Factor Rev 2007; 18: 125-134
• 30 Orman MA, Nguyen TT, Ierapetritou MG, Berthiaume F, Androulakis IP. Comparison of the cytokine and chemokine dynamics of the early inflammatory response in models of burn injury and infection. Cytokine 2011; 55: 362-371
• 31 Mirza RE, Fang MM, Ennis WJ, Koh TJ. Blocking interleukin-1β induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes. Diabetes 2013; 62: 2579-2587
• 32 Darby IA, Hewitson TD. Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol 2007; 257: 143-179
• 33 Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Müller W, Roers A, Eming SA. Differential roles of macrophages in diverse phases of skin repair. J Immunol 2010; 184: 3964-3977
• 34 Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 2009; 27: 519-550
• 35 Hazman Ö, Ovalı S. Investigation of the anti-inflammatory effects of safranal on high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Inflammation 2015; 38: 1012-1019
• 36 Goel A, Shrivastava P. Post-burn scars and scar contractures. Indian J Plast Surg 2010; 43: S63
• 37 Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, Wu FZ, Cheng Y, Xiang LJ, Guo DJ, Luo X. The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo . PLoS One 2013; 8: e59966
• 38 Spyrou GE, Naylor IL. The effect of basic fibroblast growth factor on scarring. J Plast Reconstr Aesthet Surg 2002; 55: 275-282
• 39 Muhammad A, Pauzi N, Arulselvan P, Abas F, Fakurazi S. In vitro wound healing potential and identification of bioactive compounds from Moringa oleifera Lam. Biomed Res Int 2013; 2013: 1-10
• 40 Oryan A, Goodship AE, Silver IA. Response of a collagenase-induced tendon injury to treatment with a polysulphated glycosaminoglycan (Adequan). Connect Tissue Res 2008; 49: 351-360
• 41 Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR. Topical application of Aloe vera accelerated wound healing, modeling, and remodeling: an experimental study. Ann Plast Surg 2016; 77: 37-46
• 42 Tabandeh MR, Oryan A, Mohammadalipour A. Polysaccharides of Aloe vera induce MMP-3 and TIMP-2 gene expression during the skin wound repair of rat. Int J Biol Macromolec 2014; 65: 424-430
• 43 Oryan A, Silver IA, Goodship AE. Effects of a serotonin S2-receptor blocker on healing of acute and chronic tendon injuries. J Invest Surg 2009; 22: 246-255
• 44 Oryan A, Moshiri A, Meimandiparizi AH. Effects of sodium-hyaluronate and glucosamine-chondroitin sulfate on remodeling stage of tenotomized superficial digital flexor tendon in rabbits: a clinical, histopathological, ultrastructural, and biomechanical study. Connect Tissue Res 2011; 52: 329-339