Nafise HANAFI, Fereshteh TALEBPOURAMIRI, Somayeh SHAHANI, Reza ENAYATIFARD, Maryam GHASEMI, Abbas Ali KARIMPOUR

Licorice cream promotes full-thickness wound healing in Guinea pigs

Impaired wound healing may cause economic and social problems and seriously reduce the quality of life. The uses of herbal medicines as new alternative treatments are under investigation. This study investigated the effect of Glycyrrhiza glabra L. extract on the full-thickness wound healing in Guinea Pig model.Eight male Guinea Pigs (700-800 g) were used to be creared a square full-thickness wound with 1.5 ×1.5 dimensions on the lumbodorsal area. The wounds were randomly divided into four groups: I; control, II; 1% phenytoin, III; 5% G. glabraand IV; 10 % G.glabra. On day 3, 5, 7, 9 and 12, wound size was measured for assessment of the percent of wound healing. In order to determine the wound healing activity, excisional biopsies were evaluated histopathologically on the 12th days of treatments. Acute inflammation, granulation tissue fibroblast maturation, collagen deposition, epidermal layer formation, neovascularization, keratin layer formation were evaluated according to the Abramov score method. Hydroalcoholic extract ofG.glabraexhibited total phenolic and flavonoidcontents of 114.1 ± 5.45 and 82.85 ± 6.38 mg, respectively. G.glabracreams (5% and 10% w/w)were significantly increased the epidermal formation, collagen deposition and neovascularization, and was decreased acute inflammation in comparison to the control group. Wound healing rate were increased in the G. glabragroups. G.glabracreams 10 % was more effective than 5% w/w. Our findings proved that 5% and 10% w/w G. glabracreams were effective in acute dermal wound healing. More studies with different doses of G. glabraextract are recommended.

PDF

___

[1] Ghabaee DNZ, Ebrahimzadeh MA, Akbari J, Amiri FT. Wound healing activity of Sambucus ebulus.Int J Pharm Sci Res. 2017;8(1):132-135.

[2] Singh K, Agrawal NK, Gupta SK, Sinha P, Singh K. Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus (T2DM) cases with impaired wound healing. JDiabetesComplications.2016;30(1):99-108.

[3] Singh A, Halder S, Chumber S, Misra MC, Sharma LK, Srivastava A,Menon GR. Meta-analysis of randomized controlled trials on hydrocolloid occlusive dressing versus conventional gauze dressing in the healing ofchronic wounds. Asian J Surg.2004;27(4):326-332.

[4] Mahmoudi RM, Talebpour AF, Mirhoseini M, Ghasemi M, Mirzaei M, Mosaffa N. Application of allogeneic fibroblast cultured on acellular amniotic membrane for full-thickness wound healing in rats. Wounds. 2016; 28(1): 14-19.

[5] Doersch KM, DelloStritto DJ, Newell-Rogers MK. The contribution of interleukin-2 to effective wound healing. Exp Biol Med (Maywood). 2017;242(4):384-396.

[6] Pazyar N, Yaghoobi R, Rafiee E, Mehrabian A, Feily A. Skin wound healing and phytomedicine: a review. SkinPharmacol Physiol.2014;27(6):303-310.

[7] Dorjsembe B, Lee HJ, Kim M, Dulamjav B, Jigjid T, Nho CW. Achillea asiatica extract and its active compounds induce cutaneous wound healing. J Ethnopharmacol. 2017;206:306-314.

[8] dos Santos Gramma LS, Marques FM, Vittorazzi C, de Andrade TAM, Frade MAC, de Andrade TU, Endringer DC,Scherer R,Fronza M.Struthanthus vulgarisointment prevents an over expression of inflammatory response and accelerates the cutaneous wound healing. J Ethnopharmacol.2016;190:319-327.

[9] Komes D, Belščak-Cvitanović A, Jurić S, Bušić A, Vojvodić A, Durgo K. Consumer acceptability of liquorice root (Glycyrrhiza glabraL.) as an alternative sweetener and correlation with its bioactive content and biological activity. Int J Food Sci Nutr.2016;67(1):53-66.

[10] Jeon J-S, Kim H-T, Kim M-G, Oh M-S, Hong S-R, Yoon M-H, Shin H-S, Shim J-H, Afifi NA, Hacimuftuoglu A, Aty AMAE. Simultaneous detection of Glabridin, (−)-α-Bisabolol, and Ascorbyl tetraisopalmitate in whitening cosmetic creams using HPLC-PAD. Chromatographia. 2016;79(13-14):851-860.

[11] Sharma H, Yunus G, Agrawal R, Kalra M, Verma S, Bhattar S. Antifungal efficacy of three medicinal plants Glycyrrhiza glabra, Ficus religiosa, and Plantago majoragainst oral Candida albicans: A comparative analysis. Indian J Dent Res. 2016;27(4):433-436.

[12] Sharma H, Yunus G, Mohapatra AK, Kulshrestha R, Agrawal R, Kalra M. Antimicrobial efficacy of three medicinal plants Glycyrrhiza glabra, Ficus religiosa, and Plantago majoron inhibiting primary plaque colonizers and periodontal pathogens: An in vitrostudy. Indian J Dent Res.2016;27(2):200-204.

[13] Fukuchi K, Okudaira N, Adachi K, Odai-Ide R, Watanabe S, Ohno H, Yamamoto M,Kanamoto T,Terakubo S,Nakashima H,Uesawa Y,Kagaya H,Sakagami H. Antiviral and antitumor activity of Licorice root extracts. In Vivo. 2016;30(6):777-785.

[14] Tanideh N, Rokhsari P, Mehrabani D, Mohammadi Samani S, Sabet Sarvestani F, Ashraf MJ, Hosseinabadi OK,Shamsian S,Ahmadi N. The healing effect of licorice on Pseudomonas aeruginosainfected burn wounds in experimental rat model. World J Plast Surg. 2014;3(2):99-106.

[15] Tanaka A, Horiuchi M, Umano K, Shibamoto T. Antioxidant and anti‐inflammatory activities of water distillate and its dichloromethane extract from licorice root (Glycyrrhiza uralensis) and chemical composition of dichloromethane extract. J Sci Food Agri. 2008;88(7):1158-1165.

[16] Chen X, Fang D, Li L, Chen L, Li Q, Gong F, Fang M.Glycyrrhizin ameliorates experimental colitis through attenuating interleukin-17-producing T cell responses via regulating antigen-presenting cells. Immunol Res.2017;65(3):666-680.

[17] Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008;22(6):709-724.

[18] Simmler C, Pauli GF, Chen S-N. Phytochemistry and biological properties of glabridin. Fitoterapia . 2013;90:160-184.

[19] Oloumi MM, Derakhshanfar A, NikpoorA. Healing potential of liquorice root extract on dermal wounds in rats. J Vet Res. 2007;62(4):147-154.

[20] Memariani Z, Hajimahmoodi M, Minaee B, Khodagholi F, Yans A, Rahimi R,,Amin G,Moghaddam G,Toliyat T,Sharifzadeh M. Protective effect of a polyherbal traditional formula consisting of Rosa damascenaMill., Glycyrrhiza glabraL. and Nardostachys jatamansi DC., against ethanol-induced gastric ulcer. Iran J Pharm Res.2017;16(2):694-707.

[21] Najeeb VD, Al-Refai AS. Antibacterial effect and healing potential of topically applied licorice root extract on experimentally induced oral wounds in rabbits. Saudi J Oral Sci. 2015;2(1):10-13.

[22] Tanideh N, Rokhsari P, Mehrabani D, Mohammadi Samani S, Sabet Sarvestani F, Ashraf MJ, Hosseinabadi OK,Shamsian S,Ahmadi N. The healing effect of licorice on Pseudomonas aeruginosa infected burn wounds in experimental rat model. World J Plast Surg . 2014;3(2):99-106.

[23] Alhusein N, Blagbrough IS, Beeton ML, Bolhuis A, Paul A. Electrospun zein/PCL fibrous matrices release tetracycline in a controlled manner, killing Staphylococcus aureusboth in biofilms and ex vivoon pig skin, and are compatible with human skin cells. Pharm Res. 2016;33(1):237-246.

[24] Francis NK, Pawar HS, Peter N, Biswas G, Majumdar J, Mitra A. Evaluation of wound healing and antimicrobial physiognomies of alcoholic extract of Ocimum sanctum(basil) in diabetic rabbit model. Int J Herb Med. 2017;5(2):91-97.

[25] Getie M, Gebre-Mariam T, Rietz R, Neubert R. Evaluation of the release profiles of flavonoids from topical formulations of the crude extract of the leaves of Dodonea viscosa (Sapindaceae). Pharmazie . 2002;57(5):320-322.

[26] Xue M, Jackson CJ. Extracellular matrix reorganization during wound healing and its impact on abnormal scarring. AdvWoundCare (New Rochelle).2015;4(3):119-136.

[27] Lodhi S, Jain A, Jain AP, Pawar RS, Singhai AK. Effects of flavonoids from Martynia annuaand Tephrosia purpureaon cutaneous wound healing. Avicenna J Phytomed. 2016;6(5):578-591.

[28] Oliveira RN, Mancini MC, Oliveira FCSd, Passos TM, Quilty B, Thiré RMdSM, McGuinness GB. FTIR analysis and quantification of phenols and flavonoids of five commercially available plants extracts used in wound healing. Matéria (Rio J.). 2016;21(3):767-779.

[29] Hasamnis AA, Mohanty BK, Patil S. Evaluation of wound healing effect of topical phenytoin on excisional wound in albino rats. J Young Pharm. 2010;2(1):59-62.

[30] Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008; 454(7203): 436-444.

[31] Loni F, Maghsodi H, Shiri S. The effect of Glycirrhiza glabra on osteoarthritis: suppression of TNF-a, IL-1b, Cox-2, iNOS gene expression and prostaglandin E2 and nitric oxide production in chondrocytes and monocyte/macrophages. Healt Biotech Biopharma. 2017;1(2): 70-82.

[32] Lim HS, Yo SR, Lee MY, Seo CS, Shin HK, Jeong SJ. Potential inhibitory effects of the traditional herbal prescription Hyangsosan against skin inflammation via inhibition of chemokine production and inactivation of STAT1 in HaCaT keratinocytes. Mol Med Rep. 2017; 2515-2522.

[33] Okda FA, Yassein S, Ahmed AR, Soufy H, Nasr SM. Some haematological and biochemical investigations on duck virus hepatitis following administration of glycyrrhizin. ISRN Pharmacol.2013;2013: 849471..

[34] Castangia I, Caddeo C, Manca ML, Casu L, Latorre AC, Díez-Sales O,Saurí AR, Bacchetta G, Fadda AM, ManconiM. Delivery of liquorice extract by liposomes and hyalurosomes to protect the skin against oxidative stress injuries. Carbohydr Polym. 2015;134:657-663.

[35] Shen L, Cui Z, Lin Y, Wang S, Zheng D, Tan Q. Anti-inflammative effect of glycyrrhizin on rat thermal injury via inhibition of high-mobility group box 1 protein. Burns. 2015;41(2):372-378.

[36] Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29:139-162.

[37] Matsui S, Matsumoto H, Sonoda Y, Ando K, Aizu-Yokota E, Sato T, Kasahara T . Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. Int Immunopharmacol. 2004;4(13):1633-1644.

[38] Majtan J, Bohova J, Garcia-Villalba R, Tomas-Barberan FA, Madakova Z, Majtan T, Majtan V,Klaudiny J. Fir honeydew honey flavonoids inhibit TNF-α-induced MMP-9 expression in human keratinocytes: a new action of honey in wound healing. Arch Dermatol Res. 2013;305(7):619-627.

[39] Hsieh MJ, Lin CW, Yang SF, Chen MK, Chiou HL. Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF‐κB and AP‐1 activity in human liver cancer cells. Br J Pharmacol.2014;171(12):3037-3050.

[40] Cetin E, Yesil-Celiktas O, Cavusoglu T, Demirel-Sezer E, Akdemir O, Uyanikgil Y. Incision wound healing activity of pine bark extract containing topical formulations: A study with histopathological and biochemical analyses in albino rats. Int J Pharm Sci. 2013;68(1):75-80.

[41] Aly UF, Mansour HF. Novel Pharmaceutical gels containing glyccerihizic acid ammonium salt for chronic wounds. Br J Pharm Res. 2014;4(5):654-668.

[42] 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.

[43] Miliauskas G, Venskutonis P, Van Beek T. Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chem. 2004;85(2):231-237.

[44] Silva MCAd, Paiva SR. Antioxidant activity and flavonoid content of Clusia fluminensis Planch. & Triana. An Acad Bras Cienc 2012;84(3):609-616.

[45] Amiri FT, Fathabadi FF, Rad MM, Piryae A, Ghasemi A, Khalilian A, YeganehF,MosaffaN . The effects of insulin-like growth factor-1 gene therapy and cell transplantation on rat acute wound model. Iran Red Crescent Med J. 2014;16(10):e16323.

[46] Abramov Y, Golden B, Sullivan M, Botros SM, Miller JJR, Alshahrour A,Goldberg RP, Sand PK. Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model. WoundRep Reg. 2007;15(1):80-86.