Wound healing activity of Combination Propolis and Coconut Shell Liquid Smoke Ointment on wistar rat second degree Burns wound models
Abstract
Introduction: The delay in burns healing is a serious complication that can lead to disability and death. TGF-?1 contributes significantly to the wound healing process. Chronic wounds that do not heal often indicate a loss of TGF-?1 signaling. Propolis and coconut shell liquid smoke (CS-LS) are natural ingredients that contain antioxidant, anti-inflammatory, and analgesic compounds to accelerate wound healing. This study aimed to prove the effectiveness of using a topical combination of propolis and CS-LS in accelerating the healing process of degree II burns and their relationship with the expression of TGF-?1 in serum. Method: A 14-day in vivo experimental investigation using Wistar rats was carried out with a total sample of 25 rats divided into 4 groups.; Group 1, treated with sulfadiazine ointment; Group 2, treated with propolis ointment; Group 3, treated with CS-LS ointment; Group 4, treated with the combination of propolis and CS-LS ointment, and 1 control group without treatment. Serum TGF-?1 levels were determined by ELISA.
Result: Measurements of wound size were on days 0,3,7 and 14. This study obtained results the combination ointment group alone had significantly different TGF-?1 levels from day 7 to day 14 and experienced a decrease in TGF-?1 levels of 52.28 ?/mg. Based on wound size, there was a significant difference in all groups (p<0.05), this was supported by the mean value of wound size which was smaller in the sulfadiazine ointment group and the combination (propolis and liquid smoke) ointment group.
Conclusion: The combination of propolis and coconut shell liquid smoke can be considered as an alternative in the treatment of second degree burns because of its ability to reduce TGF-?1 and accelerate burn wound healing.
Keywords: wound healing, propolis, coconut shell liquid smoke, TGF-?1
References
2. Olczyk P, Komosinska-Vassev K, Wisowski G et al. (2014) Propolis modulates fibronectin expression in the matrix of thermal injury. Biomed Res Int. doi: 10.1155/2014/748101
3. Phan TT, Lee ST, Chan SY et al. (2000) Investigating plant-based medicines for wound healing with the use of cell culture technologies and in vitro models: A review. Ann Acad Med Singap 29
4. Macleod AS, Mansbridge JN (2015) The Innate Immune System in Acute and Chronic Wounds. 5 (2): 65–78. doi: 10.1089/wound.2014.0608.
5. Phan TT, Lee ST, Frcs MA et al. (2000) Investigating Plant-based Medicines for Wound Healing with the Use of Cell Culture Technologies and In vitro Models?: A Review. 29 (1): 27–36.
6. Markiewicz-Gospodarek A, Kozio? M, Tobiasz M et al. (2022) Burn Wound Healing: Clinical Complications, Medical Care, Treatment, and Dressing Types: The Current State of Knowledge for Clinical Practice. Int J Environ Res Public Health. doi: 10.3390/ijerph19031338
7. Pastar I, Stojadinovic O, Krzyzanowska A et al. Attenuation of the Transforming Growth Factor ? – Signaling Pathway in Chronic Venous Ulcers. doi: 10.2119/molmed.2009.00149
8. Penn JW, Grobbelaar AO, Rolfe KJ (2012) The role of the TGF- ? family in wound healing , burns and scarring?: a review. 2 (1): 18–28.
9. kim, byung-chul?; kim heung tae?; park seok hee (2003) Fibroblasts from chronic wounds show altered TGF? ?signaling and decreased TGF?.pdf. 331–336. doi: 10.1002/jcp.10301.
10. Vaidyanathan L (2021) Growth Factors in Wound Healing – A Review. 14 (September): 1469–1480.
11. Yang J, Pi A, Yan L et al. (2022) Research Progress on Therapeutic Effect and Mechanism of Propolis on Wound Healing. Evidence-Based Complementary and Alternative Medicine 2022 5798941. doi: 10.1155/2022/5798941.
12. Iswanto H, Kuswandari S, Putri Kusuma Wardani Mahendra dan et al. Kajian Pada Anak Usia 6-10 Tahun.
13. Bhargava P, Mahanta D, Kaul A et al. (2021) Experimental evidence for therapeutic potentials of propolis. Nutrients 13 (8): 1–23. doi: 10.3390/nu13082528.
14. Henshaw FR, Bolton T, Nube V et al. (2014) Topical application of the bee hive protectant propolis is well tolerated and improves human diabetic foot ulcer healing in a prospective feasibility study. Journal of diabetes and its complications 28 (6): 850–857. doi: 10.1016/J.JDIACOMP.2014.07.012.
15. Mawarti H PENGARUH FLAVONOID PROPOLIS TERHADAP LAMA PENYEMBUHAN LUKA BAKAR GRADE II PADA TIKUS PUTIH.
16. Iyyam Pillai S, Palsamy P, Subramanian S, Kandaswamy M (2010) Wound healing properties of Indian propolis studied on excision wound-induced rats. Pharmaceutical biology 48 (11): 1198–1206. doi: 10.3109/13880200903578754.
17. Martinotti S, Ranzato E (2015) Propolis: A new frontier for wound healing? Burns and Trauma 3 (1): 1–7. doi: 10.1186/s41038-015-0010-z.
18. Lima EBC, Sousa CNS, Meneses LN et al. (2015) Cocos nucifera (L.) (arecaceae): A phytochemical and pharmacological review. Brazilian Journal of Medical and Biological Research 48 (11): 953–964. doi: 10.1590/1414-431X20154773.
19. Budijanto S, Hasbullah R, Sulusi P (2008) uji keamanan asap tempurung. Pascapanen Journal 5 (1): 32–40.
20. surboyo meircurius, Ernawati DS, Arundina D (2021) The potential of liquid smoke as an oral ulcer remedies: A proposed mechanism based on systematic review. J Pharm Pharmacogn Res
21. Febriyanti Ayuningtyas N, Dwi Condro Surboyo M, Savitri Ernawati D et al. (2020) The role of liquid smoke coconut shell in the proliferation phase of an oral traumatic ulcer. Journal of Pharmacy & Pharmacognosy Research 8 (6): 549–557.
22. Surboyo MDC, Arundina I, Rahayu RP et al. (2019) Potential of Distilled Liquid Smoke Derived from Coconut (Cocos nucifera L) Shell for Traumatic Ulcer Healing in Diabetic Rats. European Journal of Dentistry 13 (2): 271–279. doi: 10.1055/s-0039-1693527.
23. Febriyanti Ayuningtyas N, Dwi Condro Surboyo M, Savitri Ernawati D et al. (2020) The role of liquid smoke coconut shell in the proliferation phase of an oral traumatic ulcer. Journal of Pharmacy & Pharmacognosy Research 8 (6): 549–557.
24. Arief H, Aris M, Bagian W et al. Peranan Stres Oksidatif Pada Proses Penyembuhan Luka.
25. Kotani K, Tsuzaki K, Sakane N The Relationship Between Gamma-Glutamyltransferase (GGT), Bilirubin (Bil) and Small Dense Low-Density Lipoprotein (sdLDL) in Asymptomatic Subjects Attending a Clinic for Screening Dyslipidaemias.
26. Hozzein WN, Badr G, Al Ghamdi AA et al. (2015) Topical application of propolis enhances cutaneous wound healing by promoting TGF-beta/smad-mediated collagen production in a streptozotocin-induced type I diabetic mouse model. Cellular Physiology and Biochemistry 37 (3): 940–954. doi: 10.1159/000430221.
27. Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A (2013) Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing. Advances in Wound Care 2 (5): 215–224. doi: 10.1089/wound.2012.0406.
28. Liu YC, Hsiao HT, Wang JCF et al. (2022) TGF-?1 in plasma and cerebrospinal fluid can be used as a biological indicator of chronic pain in patients with osteoarthritis. PLoS One. doi: 10.1371/journal.pone.0262074
29. Papadimitriou A, Peixoto EBMI, Silva KC et al. (2014) Inactivation of AMPK mediates high phosphate-induced extracellular matrix accumulation via NOX4/TGFß-1 signaling in human mesangial cells. Cellular physiology and biochemistry?: international journal of experimental cellular physiology, biochemistry, and pharmacology 34 (4): 1260–1272. doi: 10.1159/000366336.
30. Hata A, Chen YG (2016) TGF-? signaling from receptors to smads. Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a022061
31. Papadimitriou A, Peixoto EBMI, Silva KC et al. (2014) Inactivation of AMPK mediates high phosphate-induced extracellular matrix accumulation via NOX4/TGF?-1 signaling in human mesangial cells. Cellular Physiology and Biochemistry 34 (4): 1260–1272. doi: 10.1159/000366336.
32. Abu-Seida AM (2015) Effect of propolis on experimental cutaneous wound healing in dogs. Vet Med Int. doi: 10.1155/2015/672643
33. Pasupuleti VR, Sammugam L, Ramesh N, Gan SH (2017) Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits. Oxid Med Cell Longev. doi: 10.1155/2017/1259510
34. Bhargava P, Mahanta D, Kaul A et al. (2021) Experimental evidence for therapeutic potentials of propolis. Nutrients. doi: 10.3390/nu13082528
35. Surboyo MDC, Arundina I, Rahayu RP et al. (2019) Potential of Distilled Liquid Smoke Derived from Coconut (Cocos nucifera L) Shell for Traumatic Ulcer Healing in Diabetic Rats. European Journal of Dentistry 13 (2): 271–279. doi: 10.1055/s-0039-1693527.
36. Tarawan VM, Mantilidewi KI, Dhini IM et al. (2017) Coconut Shell Liquid Smoke Promotes Burn Wound Healing. Journal of Evidence-Based Complementary and Alternative Medicine 22 (3): 436–440. doi: 10.1177/2156587216674313.
37. Tan WS, Arulselvan P, Ng SF et al. (2019) Improvement of diabetic wound healing by topical application of Vicenin-2 hydrocolloid film on Sprague Dawley rats 11 Medical and Health Sciences 1103 Clinical Sciences. BMC Complement Altern Med. doi: 10.1186/s12906-018-2427-y
38. Scozzafava A, Passaponti M, Supuran CT, Gülçin I (2015) Carbonic anhydrase inhibitors: Guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII). Journal of Enzyme Inhibition and Medicinal Chemistry 30 (4): 586–591. doi: 10.3109/14756366.2014.956310.
39. Rorison P, Thomlinson A, Hassan Z et al. (2010) Longitudinal changes in plasma Transforming growth factor beta-1 and post-burn scarring in children. Burns 36 (1): 89–96. doi: 10.1016/J.BURNS.2009.03.008.
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