ALLOKSAN İLE DİYABET OLUŞTURULMUŞ FARELERDE NARİNGİN JELİN YARA İYİLEŞTİRİCİ ETKİLERİ

Year 2020, Volume: 44 Issue: 3, 397 - 414, 30.09.2020

Mehmet Evren Okur , Ayşe Arzu Şakul Şule Ayla , Ayşe Esra Karadağ , Cemre Şahin Şenyüz Şebnem Batur , Benay Daylan Ekrem Musa Özdemir Şaziye Sezin Yücelik , Hande Sipahi , Ahmet Aydın

https://doi.org/10.33483/jfpau.742224

Cited By: 3

Abstract

Amaç: Bu çalışmanın amacı, bir flavonoid olan Naringin’in in vitro sitotoksisite, irritasyon ile diyabetik yara üzerindeki in vivo potansiyel etkilerini araştırmaktı.

Gereç ve Yöntem: Naringin'in irritasyon ve sitotoksisite potansiyelini değerlendirmek için in vitro doğrudan temas deneyi ve tavuk yumurtası korio-allantoin membran testleri kullanıldı. Aynı zamanda in vitro antimikrobiyal etkinlikte test edildi. Topikal tedaviler günde bir kez yaraya uygulandı. Yara lezyonları fotoğraflandı ve istatistiksel olarak analiz edildi. 10. günden sonra dokuların histopatolojik parametreleri değerlendirildi.

Sonuç ve Tartışma: Sonuçlar, naringin jelin sitotoksisite ve tahriş potansiyeli olmadığını göstermiştir. Ayrıca, zayıf bir antimikrobiyal etki gösterdi. Bunların yanı sıra, in vivo çalışmalar naringin jelin istatistiksel olarak daha yüksek yara kapanması ve re-epitelyalizasyon, granülasyon dokusunun kalınlığı ve anjiyogenez skorları gösterdiğini ortaya koymuştur. Sonuçlar, naringin jelin diyabetik yara iyileşmesini etkili bir şekilde arttırdığını gösterdi ve bu nedenle bu formülasyon, diyabetik yaraların tedavisi için umut verici bir terapötik alternatif olarak düşünülebilir.

Keywords

Diabetes mellitus, HET-CAM, Hücre kültürü, Naringin, Yara iyileşmesi

WOUND HEALING EFFECT OF NARINGIN GEL IN ALLOXAN INDUCED DIABETIC MICE

Abstract

Objective: The aim of this study was to investigate the effects of naringin, a known flavonoid, on in vitro cytotoxicity, irritation and in vivo potential efficacy when topically applied to the diabetic wound.

Material and Method: In vitro direct contact assay and hen’s egg chorio-allantoin membrane tests were used to evaluate irritation, and cytotoxicity potential of Naringin. In vitro antimicrobial activity was also tested. Topical treatments were administered once a day on the wound. Wound lesions were photographed and statistically analyzed. After the 10th day, histopathological parameters of tissues were assessed. 

Result and Discussion: The results showed that naringin gel has no cytotoxicity and irritation potential. Also, it displayed a weak antimicrobial effect. Aside from these, in vivo studies revealed that naringin gel showed statistically higher wound contraction and re-epithelialization, the thickness of granulation tissue, angiogenesis scores. The results indicated that naringin gel effectively enhanced diabetic wound healing, and so this formulation could be considered a promising therapeutic alternative for treating diabetic wounds.

Keywords

Cell culture, Diabetes mellitus, HET-CAM, Naringin, Wound healing

References

• 1. Okur, M.E., Karantas, I.D., Siafaka, P.I. (2017). Diabetes Mellitus: A Review on Pathophysiology, Current Status of Oral Pathophysiology, Current Status of Oral Medications and Future Perspectives. Acta Pharmaceutica Sciencia, 55, 61.
• 2. Shah, S.A., Sohail, M., Khan, S., Minhas, M.U., de Matas, M., Sikstone, V., Hussain Z., Abbasi M., Kousar M.et al. (2019). Biopolymer-based biomaterials for accelerated diabetic wound healing: A critical review. International Journal of Biological Macromolecules, 139, 975–993.
• 3. Siafaka, P.I., Zisi, A.P., Exindari, M.K., Karantas, I.D., Bikiaris, D.N. (2016). Porous dressings of modified chitosan with poly(2-hydroxyethyl acrylate) for topical wound delivery of levofloxacin. Carbohydrate Polymers, 143, 90–99.
• 4. Veith, A.P., Henderson, K., Spencer, A., Sligar, A.D., Baker, A.B. (2019). Therapeutic strategies for enhancing angiogenesis in wound healing. Advanced Drug Delivery Reviews, 146, 97–125.
• 5. Okur, M.E., Karantas, I.D., Şenyiğit, Z., Okur, N.Ü., Siafaka, P.I. (2020). Recent trends on wound management; new therapeutic choices based on polymeric carriers. Asian Journal of Pharmaceutical Sciences, January 23, 2020
• 6. Rao, S.S., Venkatesan, J., Prabhu, A., Rekha, P.D. (2020). Natural polymeric biomaterials in growth factor delivery for treating diabetic foot ulcers. Journal of Drug Delivery Science and Technology, 55, 101385.
• 7. Cho, H., Blatchley, M.R., Duh, E.J., Gerecht, S. (2019). Acellular and cellular approaches to improve diabetic wound healing. Advanced Drug Delivery Reviews, 146, 267–288.
• 8. Kandhare, A.D., Ghosh, P., Bodhankar, S.L. (2014). Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats. Chemico-Biological Interactions, 219, 101–112.
• 9. Gadelkarim, M., Abushouk, A.I., Ghanem, E., Hamaad, A.M., Saad, A.M. and Abdel-Daim, M.M. (2018). Adipose-derived stem cells: Effectiveness and advances in delivery in diabetic wound healing. Biomedicine and Pharmacotherapy, 107, 625–633.
• 10. Ahmed, O.M., Mohamed, T., Moustafa, H., Hamdy, H., Ahmed, R.R. and Aboud, E. (2018). Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress. Biomedicine and Pharmacotherapy, 101, 58–73.
• 11. Özay, Y., Güzel, S., Yumrutaş, Ö., Pehlivanoğlu, B., Erdoğdu, İ.H., Yildirim, Z., Türk, B.A., Darcan, S. (2019). Wound healing effect of kaempferol in diabetic and nondiabetic rats. Journal of Surgical Research, 233, 284–296.
• 12. Kandhare, A.D., Alam, J., Patil, M.V.K., Sinha, A. and Bodhankar, S.L. (2016). Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats. Pharmaceutical Biology, 54, 419–432.
• 13. Karadağ, A.E., Demirci, B., Çaşkurlu, A., Demirci, F., Okur, M.E., Orak, D., Sipahi, H., Başer, K. H. C. (2019). In vitro antibacterial, antioxidant, anti-inflammatory and analgesic evaluation of Rosmarinus officinalis L. flower extract fractions. South African Journal of Botany, 125, 214–220.
• 14. Siafaka, P., Okur, M.E., Ayla, Ş., Er, S., Cağlar, E.Ş. (2019). Design and characterization of nanocarriers loaded with Levofloxacin for enhanced antimicrobial activity ; physicochemical properties , in vitro release and oral acute toxicity. Brazilian Journal of Pharmaceutical Sciences, 55, 1–13.
• 15. Standardization, C.-E.C. for (2009). ISO 10993-5:2009 - Biological evaluation of medical devices- Part 5: Tests for in vitro cytotoxicity. https://www.iso.org/standard/36406.html (21 April 2020).
• 16. Üstündağ Okur, N., Filippousi, M., Okur, M.E., Ayla, Ş., Çağlar, E.Ş., Yoltaş, A., Siafaka, P.I. (2018). A novel approach for skin infections: Controlled release topical mats of poly(lactic acid)/poly(ethylene succinate) blends containing Voriconazole. Journal of Drug Delivery Science and Technology, 46, 74–86.
• 17. HET-CAM (2010). ICCVAM-Recommended Test Method Protocol: Hen’s Egg Test-Chorioallantoic Membrane (HET-CAM) Test Method.
• 18. Okur, M.E., Polat, D.C., Ozbek, H., Yilmaz, S., Yoltas, A., Arslan, R. (2018). Evaluation of the antidiabetic property of capparis ovata desf. Var. Paleastina zoh. Extracts using in vivo and in vitro approaches. Endocrine, Metabolic & Immune Disorders - Drug Targets, 18, 489–501.
• 19. Okur, M.E., Ayla, Ş., Çiçek Polat, D., Günal, M.Y., Yoltaş, A. and Biçeroğlu, Ö. (2018). Novel insight into wound healing properties of methanol extract of Capparis ovata Desf. var. palaestina Zohary fruits. Journal of Pharmacy and Pharmacology, 70, 1401–1413.
• 20. Galeano, M., Altavilla, D., Bitto, A., Minutoli, L., Calò, M., Cascio, P. Lo, et al. (2006). Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds*. Critical Care Medicine, 34, 1139–1146.
• 21. Özçelik, B., Kartal, M., Orhan, I. (2011). Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharmaceutical Biology, 49, 396–402.
• 22. Budovsky, A., Yarmolinsky, L., Ben-Shabat, S. (2015). Effect of medicinal plants on wound healing. Wound Repair and Regeneration, 23, 171–183.
• 23. Gutiérrez-Venegas, G., Gómez-Mora, J.A., Meraz-Rodríguez, M.A., Flores-Sánchez, M.A., Ortiz-Miranda, L.F. (2019). Effect of flavonoids on antimicrobial activity of microorganisms present in dental plaque. Heliyon, 5(12), e03013.
• 24. Jang, M.H., Piao, X.L., Kim, J.M., Kwon, S.W., Park, J.H. (2008). Inhibition of cholinesterase and amyloid-&bgr; aggregation by resveratrol oligomers from Vitis amurensis. Phytotherapy Research, 22, 544–549.
• 25. Ishaka, A., Ismail, M., Imam, M.U., Mahmud, R., Sani, I.M., Zakaria, Z.A.B. (2017). Toxicity Evaluation, HET-CAM Irritation, and Anti-Irritant Potential of Rice Bran Wax Policosanol Nanoemulsion. Journal of Nano Research, 49, 44–55.
• 26. Auner, B.G., Wirth, M., Valenta, C. (2005). Antioxidative activity and cytotoxicity of four different flavonoids for dermal applications. Journal of Drug Delivery Science and Technology, 15, 227–232.
• 27. Fan, H., Zhang, P., Zhou, L., Mo, F., Jin, Z., Ma, J., Lin, R., Liu, Y., Zhang J. (2020). Naringin-loaded polymeric micelles as buccal tablets: formulation, characterization, in vitro release, cytotoxicity and histopathology studies. Pharmaceutical Development and Technology, 25(5),547-555.
• 28. Sipahi, H., Reis, R., Dinc, O., Kavaz, T., Dimoglo, A., Aydın, A. (2019). In vitro biocompatibility study approaches to evaluate the safety profile of electrolyzed water for skin and eye. Human and Experimental Toxicology, 38, 1314–1326.
• 29. Dahl, J.E. (1999). Irritation of dental adhesive agents evaluated by the HET-CAM test. Toxicology in Vitro, 13, 259–264.
• 30. Liu, W.Y., Tzeng, T.F., Liu, I.M. (2017). Healing potential of zerumbone ointment on experimental full-thickness excision cutaneous wounds in rat. Journal of Tissue Viability, 26, 202–207.
• 31. Suriyamoorthy, S., Subramaniam, K., Jeevan Raj Durai, S., Wahaab, F., Pemila Edith Chitraselvi, R. (2014). Evaluation of wound healing activity of Acacia caesia in rats. Wound Medicine, 7, 1–7.
• 32. Abu-Al-Basal, M.A. (2010). Healing potential of Rosmarinus officinalis L. on full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice. Journal of Ethnopharmacology, 131, 443–450.
• 33. Patel, S., Srivastava, S., Singh, M.R., Singh, D. (2019). Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomedicine and Pharmacotherapy, 112, 108615.
• 34. Devalliere, J., Dooley, K., Yu, Y., Kelangi, S.S., Uygun, B.E., Yarmush, M.L. (2017). Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice. Biomaterials, 141, 149–160.