Effect of ethanol extract of Lycoperdon lividum on burn injury induced in rat model

Year 2026, Volume: 30 Issue: 2, 442 - 466, 15.03.2026

Mohammed Radhi Thammer Hayder B. Sahib

https://doi.org/10.12991/jrespharm.1909866

https://izlik.org/JA33WZ37LF

Abstract

Thermal burn injury causes inflammatory cell infiltration in the dermis and epidermal thickening. Subsequent to a burn injury, numerous inflammatory mediators and cytokines, including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF), are generated, subjecting all tissues to oxidative damage. The objective of the current study is to examine the therapeutic efficacy of ethanol extract of Lycoperdon lividum on burn injuries, by assessing the wound healing and the inflammatory response by the use of rat model that grouped into five groups each of fifteen rats that further sub-divided into three groups each of five rats that sacrificed at day five, ten and twenty, respectively. Area size of burn was measured at days five, ten and twenty of experiment. Skin biopsies was taken for tissue homogenate and histopathological studies. Levels of IL-10, IL-6 and TNF-α, TGF-β and VEGF were measured in the homogenate by enzyme linked immunosorbent assay (ELISA). Result showed that ethanol extract of Lycoperdon lividum has good anti- inflammatory, proliferative effect and shortening time of wound healing by decreasing proinflammatory mediator like IL-6 and TNF-α and enhance the expression of anti-inflammatory mediator like IL-10 also has modulatory effect on TGF- β and VEGF. Area size of burn measurement showed significant area contraction after treatment with ethanol extract ointment in comparison to other groups with a significant decrease in inflammatory marker after treatment with ethanol extract of Lycoperdon lividum. Histopathological finding showed that there is significant decrease in inflammation, granulation and significant increase in fibrous tissue after application of ethanol extract ointment in comparison to other groups. The findings of this study revealed that the ethanol extract of Lycoperdon Lividum exhibit significant burns healing activities.

Keywords

lycoperdon lividum , IL-10 , IL-6 , TNF-α , TGF-β , VEGF

References

• [1] Kanitakis J. Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol. 2002;12(4):390- 399.
• [2] Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, Logsetty S. Burn injury. Nat Rev Dis Primers. 2020;6(1):11. https://doi.org/10.1038/s41572-020-0145-5
• [3] Cuttle L, Kempf M, Kravchuk O, Phillips GE, Mill J, Wang XQ, Kimble RM. The optimal temperature of first aid treatment for partial thickness burn injuries. Wound Repair Regen. 2008;16(5):626-634. https://doi.org/10.1111/j.1524-475x.2008.00413.x
• [4] Evers LH, Bhavsar D, Mailänder P. The biology of burn injury. Exp Dermatol. 2010;19(9):777-783. https://doi.org/10.1111/j.1600-0625.2010.01105.x
• [5] Thakkar V, Korat V, Baldaniya L, Gohel M, Gandhi T, Patel N. Development and characterization of novel hydrogel containing antimicrobial drug for treatment of burns. Int J Pharm Investig. 2016;6(3):158- 168. https://doi.org/10.4103/2230-973x.187343
• [6] Stensballe J, Tvede M, Looms D, Lippert FK, Dahl B, Tønnesen E, Rasmussen LS. Infection risk with nitrofurazone- impregnated urinary catheters in trauma patients: a randomized trial. Ann Intern Med. 2007;147(5):285- 293. https://doi.org/10.7326/0003-4819-147-5-200709040-00002
• [7] Khattab A, Ismail S, Abd-Elrazek AM. Mucoadhesive chitosan composite sponge as a carrier for β-sitosterol cubosomes for thermal burn treatment. AAPS PharmSciTech. 2024;25(6):148. https://doi.org/10.1208/s12249-024- 02852-4
• [8] 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(7):601-617. https://doi.org/10.1007/s00403-014-1474-6
• [9] Sevindik M, Bal C, Eraslan EC, İmran U, Mohammed FS. Medicinal mushrooms: a comprehensive study on their antiviral potential. Prosp Pharm Sc. 2023;21(2): 42–56. https://doi.org/10.56782/pps.141.
• [10] Korkmaz AI, Akgul H, Sevindik M, Selamoglu Z. Study on determination of bioactive potentials of certain lichens. Acta Aliment. 2018;47(1): 80–87. https://doi.org/10.1556/066.2018.47.1.10
• [11] Abu-Raghif AR , Qasim BJ, Abady AH, Sahib HB. Effects of aqueous thyme extract against cisplatin induced nephrotoxicity in rabbits. Int J Pharm Sci Rev Res. 2015;30(1):190-194.
• [12] Abu-Raghıf AH, Ali NM, Farhood IG, Hameed MF, SahIb HB. Evaluation of a standardized extract of Ginkgo biloba in vitiligo remedy. Asian J Pharm Clin Res. 2013;6(SUPPL.5):127-130.
• [13] Sevindik M, Akgul H, Selamoglu Z, Braidy N. Antioxidant and antigenotoxic potential of Infundibulicybe geotropa mushroom collected from northwestern Turkey. Oxid Med Cell Longev. 2020;2020:5620484. https://doi.org/10.1155/2020/5620484
• [14] Selamoglu Z, Sevindik M , Bal C, Ozaltun B, Sen I , Pasdaran A. Antioxidant, antimicrobial and DNA protection activities of phenolic content of Tricholoma virgatum (Fr.) P. Kumm. Biointerface Res Appl Chem. 2020;10(3):5500 – 5506. https://doi.org/10.33263/BRIAC103.500506
• [15] Xu J, Shen R, Jiao Z, Chen W, Peng D, Wang L, Yu N, Peng C, Cai B, Song H, Chen F, Liu B. Current advancements in antitumor properties and mechanisms of medicinal components in edible mushrooms. Nutrients. 2022 ;14(13):2622. https://doi.org/10.3390/nu14132622
• [16] Mushtaq W, Baba H, Akata I. Antioxidant potential and element contents of wild edible mushroom Suillus granulatus. KSU J Gric Nat. 2020;23(3):592-595. https://doi.org/10.18016/ksutarimdoga.vi.653241
• [17] Sevindik M. Akata I, Antioxidant, oxidant potentials and element content of edible wild mushroom Helvella leucopus. Indian J Nat Prod Resour. 2019;10(4):266-271.
• [18] Saridogan BGO , Islek C , Baba H , AKATA I , Sevindik M. Antioxidant antimicrobial oxidant and elements contents of Xylaria polymorpha and X. hypoxylon (Xylariaceae). Fresenius Environ. Bull. 2021;30(5):5400-5404.
• [19] Krupodorova, T, Sevindik M. Antioxidant potential and some mineral contents of wild edible mushroom Ramaria stricta. AgroLife Sci J. 2020;9(1):186-191.
• [20] Cheung PC. The nutritional and health benefits of mushrooms. Nutr Bull. 2010;35(4):292-299. https://doi.org/10.1111/j.1467-3010.2010.01859.x
• [21] Assemie A, Abaya G. The effect of edible mushroom on health and their biochemistry. Int J Microbiol. 2022 23;2022:8744788. https://doi.org/10.1155/2022/8744788
• [22] Bobek P, Galbavý S. Hypocholesterolemic and antiatherogenic effect of oyster mushroom (Pleurotus ostreatus) in rabbits. Nahrung. 1999;43(5):339-342. https://doi.org/10.1002/(sici)1521-3803(19991001)43:5%3C339::aid- food339%3E3.0.co;2-5
• [23] Telfer MG, Lambdon PW, Gurney M. Recent discoveries among the gasteroid fungi of Norfolk. Field Mycology. 2000;1(1):30-32. https://doi.org/10.1016/S1468-1641(10)60011-4
• [24] Shehab NG, Abu-Gharbieh E, M Almasri I. Chemical composition, docking simulations and burn wound healing effect of Micromeria fruticosa extract and its isolated flavonoidal compound. Pak J Pharm Sci. 2022;35(2):507-517.
• [25] Bhatia N, Kaur G, Soni V, Kataria J, Dhawan RK. Evaluation of the wound healing potential of isoquercetin-based cream on scald burn injury in rats. Burns Trauma. 2016;4:7. https://doi.org/10.1186/s41038-016-0032-1 Park BK, Lee S, Seo JN, Rhee JW,
• [26] Park JB, Kim YS, Choi IG, Kim YE, Lee Y, Kwon HJ. Protection of burn-induced skin injuries by the flavonoid kaempferol. BMB Rep. 2010;43(1):46-51. https://doi.org/10.5483/bmbrep.2010.43.1.046
• [27] Desai S, Sethi J, Shah H. Gallic Acid: A review on its spectrum of pharmacological activities. Int J Pharm Biol Sci. 2022;12(1): 90-100 http://dx.doi.org/10.21276/ijpbs.2022.12.1.12.
• [28] Muvhulawa N, Dludla PV, Ziqubu K, Mthembu SXH, Mthiyane F, Nkambule BB, Mazibuko-Mbeje SE. Rutin ameliorates inflammation and improves metabolic function: A comprehensive analysis of scientific literature. Pharmacol Res. 2022;178:106163. https://doi.org/10.1016/j.phrs.2022.106163
• [29] Askari G, Ghiasvand R, Feizi A, Ghanadian SM, Karimian J. The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. J Res Med Sci. 2012;17(7):637-641.
• [30] Irfan F, Jameel F, Khan I, Aslam R, Faizi S, Salim A. Role of quercetin and rutin in enhancing the therapeutic potential of mesenchymal stem cells for cold induced burn wound. Regen Ther. 2022;21:225-238. https://doi.org/10.1016/j.reth.2022.07.011
• [31] Muvhulawa N, Dludla PV, Ziqubu K, Mthembu SXH, Mthiyane F, Nkambule BB, Mazibuko-Mbeje SE. Rutin ameliorates inflammation and improves metabolic function: A comprehensive analysis of scientific literature. Pharmacol Res. 2022;178:106163. https://doi.org/10.1016/j.phrs.2022.106163
• [32] Li H, Yang L, Zhang Y, Gao Z. Kaempferol inhibits fibroblast collagen synthesis, proliferation and activation in hypertrophic scar via targeting TGF-β receptor type I. Biomed Pharmacother. 2016;83:967-974. https://doi.org/10.1016/j.biopha.2016.08.011
• [33] Tolba MF, Azab SS, Khalifa AE, Abdel-Rahman SZ, Abdel-Naim AB. Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects. IUBMB Life. 2013;65(8):699-709. https://doi.org/10.1002/iub.1189
• [34] Abhyankar SV, Vartak AM, Daftary GV. Potential role of systemic enzyme therapy with trypsin, bromelain and rutoside combination in burns. Int Surg J. 2021;8(7):2254-2259. http://dx.doi.org/10.18203/2349-2902.isj20212752
• [35] Chin HK, Horng CT, Liu YS, Lu CC, Su CY, Chen PS, Chiu HY, Tsai FJ, Shieh PC, Yang JS. Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells. Oncol Rep. 2018;39(5):2351-2357. https://doi.org/10.3892/or.2018.6312
• [36] Hu WH, Wang HY, Xia YT, Dai DK, Xiong QP, Dong TT, Duan R, Chan GK, Qin QW, Tsim KW. Kaempferol, a major flavonoid in Ginkgo folium, potentiates angiogenic functions in cultured endothelial cells by binding to vascular endothelial growth factor. Front Pharmacol. 2020;11:526. https://doi.org/10.3389/fphar.2020.00526
• [37] Kim HY, Nam SY, Hong SW, Kim MJ, Jeong HJ, Kim HM. Protective effects of rutin through regulation of vascular endothelial growth factor in allergic rhinitis. Am J Rhinol Allergy. 2015;29(3):e87- 94. https://doi.org/10.2500/ajra.2015.29.4195
• [38] Chen LY, Huang CN, Liao CK, Chang HM, Kuan YH, Tseng TJ, Yen KJ, Yang KL, Lin HC. Effects of rutin on wound healing in hyperglycemic rats. Antioxidants (Basel). 2020;9(11):1122. https://doi.org/10.3390/antiox9111122
• [39] Damiani, E, Bacchetti T, Padella L, Tiano L, Carloni P. Antioxidant activity of different white teas: Comparison of hot and cold tea infusions. J Food Compos. 2014;33(1):59-66. http://dx.doi.org/10.1016/j.jfca.2013.09.010
• [40] Canli K, Altuner EM, Akata I, Turkmen Y, Uzek U. In vitro antimicrobial screening of Lycoperdon lividum and determination of the ethanol extract composition by gas chromatography/mass spectrometry. Bangladesh J Pharmacol. 2016;11:389-394. http://dx.doi.org/10.3329/bjp.v11i2.26369.
• [41] Abd Allah FM, Moustafa AM, Moahmmed LS, Abd Allah EEDE. Histological and immunohistochemical studies on the role of stem cells on the burned skin of adult male albino rats. Int J Med Arts. 2020;2(1):265-291. https://doi.org/10.21608/ijma.2020.20386.1050.
• [42] Fatemi MJ, Garahgheshlagh SN, Ghadimi T, Jamili S, Nourani MR, Sharifi AM, Saberi M, Amini N, Sarmadi VH, Yazdi-Amirkhiz SY. Investigating the ımpact of collagen-chitosan derived from Scomberomorus Guttatus and Shrimp Skin on second-degree burn in rats model. Regen Ther. 2021;18:12-20. https://doi.org/10.1016/j.reth.2021.03.001.
• [43] Calkins CM, Bensard DD, Heimbach JK, Meng X, Shames BD, Pulido EJ, McIntyre RC Jr. L-arginine attenuates lipopolysaccharide-induced lung chemokine production. Am J Physiol Lung Cell Mol Physiol. 2001;280(3):L400- L408. https://doi.org/10.1152/ajplung.2001.280.3.l400.
• [44] Hayrapetyan H, Tran T, Tellez-Corrales E, Madiraju C. Enzyme-Linked Immunosorbent Assay: Types and Applications. Methods Mol Biol. 2023;2612:1-17. https://doi.org/10.1007/978-1-0716-2903-1_1
• [45] Ngamsuk S, Huang TC, Hsu JL. Determination of phenolic compounds, procyanidins, and antioxidant activity in processed Coffea arabica L. leaves. Foods. 2019;8(9):389. https://doi.org/10.3390/foods8090389.
• [46] Khalaf AA, Hassanen EI, Zaki AR, Tohamy AF, Ibrahim MA. Histopathological, immunohistochemical, and molecular studies for determination of wound age and vitality in rats. Int Wound J. 2019;16(6):1416-1425. https://doi.org/10.1111/iwj.13206.
• [47] Manna MJ, Jabur MS, Mohammad HR, Abdulamir HA. The potential effect of topical aminophylline on acute glaucoma model. Res J Pharm Technol. 2022; 15(1):197-200. http://dx.doi.org/10.52711/0974-360X.2022.00032.
• [48] Aldafaay AAA, Abdulamir HA, Abdulhussain HA, Badry AS, Abdulsada AK. The use of urinary α-amylase level in a diagnosis of chronic renal failure. Res J Pharm Technol. 2021; 14(3):1597-1600. http://dx.doi.org/10.5958/0974- 360X.2021.00283.3.