Herbal Products in Postsurgical Wound Healing – Incision, Excision and Dead Space Wound Models

Abstract

The purpose of this review is to summarize current knowledge acquired on preclinical (incision, excision, and dead space wound models) and clinical studies regarding topically used herbal products with wound healing activity. The antimicrobial, anti-inflammatory, and antioxidant mechanisms of their action as well as the adverse effects of herbal therapy will be described. Numerous preclinical and few clinical trials have confirmed the activity of herbal products in the stimulation of wound healing. In contrast to synthetic drugs, for which chemical compositions, purity, efficacy, minimal active concentration, and toxicity are well specified, several herbal formulations require further investigations. Nevertheless, it cannot be precluded that herbal products may be considered as an important support during conventional wound healing therapy or even as synthetic medicament replacements.

Key words

herbal products - wound healing - incision wound model - excision wound model - dead space wound model

• References

• 1 Gonzalez ACDO, Costa TF, Andrade ZDA, Medrado ARAP. Wound healing – a literature review. An Bras Dermatol 2016; 91: 614-620
• 2 Rittié L. Cellular mechanisms of skin repair in humans and other mammals. J Cell Commun Signal 2016; 10: 103-120
• 3 Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Rep Regen 2008; 16: 585-601
• 4 Caley MP, Martins VL, OʼToole EA. Metalloproteinases and wound healing. Adv Wound Care 2015; 4: 225-234
• 5 Briquez PS, Hubbell JA, Martino MM. Extracellular matrix-inspired growth factor delivery systems for skin wound healing. Adv Wound Care 2015; 4: 479-489
• 6 Pereira RF, Bartolo PJ. Traditional therapies for skin wound healing. Adv Wound Care 2016; 5: 208-229
• 7 Calixto JB. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phyto therapeutic agents). Braz J Med Biol Res 2000; 33: 179-189
• 8 Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S. A review of herbal medicines in wound healing. Int J Dermatol 2015; 54: 740-751
• 9 Budovsky A, Yarmolinsky L, Ben-Shabat S. Effect of medicinal plants on wound healing. Wound Rep Reg 2015; 23: 171-183
• 10 Kumar V, Khan AA, Nagarajan K. Animal models for the evaluation of wound healing activity. Int Bul Drug Res 2013; 3: 93-107
• 11 Laut M, Ndaong NA, Utami T. Cutaneous wound healing activity of herbal ointment containing the leaf extract of Acalypha indica L. on mice (Mus musculus). J Phys Conf Ser 2019; 1146: 012025
• 12 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
• 13 Mondal S, Ghosh D, Ganapaty S, Reddy MS, Ramakrishna K. Evaluation of healing potential of Achyranthes aspera L.(Amaranthaceae) seeds in excision, incision, dead space and burn wound model – an in vivo study. Pharmacogn J 2016; 8: 300-306
• 14 Toppo FA, Pawar RS. Appraisal on the wound healing activity of different extracts obtained from Aegle marmelos and Mucuna pruriens by in vivo experimental models. Niger J Clin Pract 2016; 19: 753-760
• 15 Misra AK, Varma SK. Effect of an extract of Agave americana on wound healing model in experimental animals. J Basic Clin Pharma 2017; 8: 45-48
• 16 Khan A, Ashfaq K, ud Din J, Ali A, Tariq A, Ghani S, Ullah N, Sulaman Y, Farooq Ahmad M. Comparative efficacy of Acacia honey and Aloe vera gel on healing of induced lacerated wound in rabbits. Am Sci Res J Eng Tech Sci 2017; 33: 182-187
• 17 Shukla R, Rai G, Jain AP. Preclinical evaluation of rhizomes for wound healing activity with Alpinia galanga reducing oxidative status. Asian J Pharm Pharmacol 2015; 1: 65-69
• 18 Natarajan S, Pattiyappan S, Rajamani R. Evaluation of C. albicans induced wound healing activity of methanolic leaf extract of Andrographis paniculata . J Sci Tech Invest 2017; 1: 39-49
• 19 Akinpelu BA, Odukoya SOA, Akanni AA, Adelodun ST, Oyedapo OO. Evaluation of wound healing activity of Achidium ohioense (Schimp. ex Mull) oil on albino rats. J Med Plant Herbal Ther Res 2018; 6: 9-30
• 20 Toporcer T, Grendel T, Vidinský B, Gal P, Sabo J, Hudák R. Mechanical properties of skin wounds after Atropa belladonna application in rats. J Met Mater Min 2017; 16: 25-29
• 21 Moron MJ, Acero LH. Mayana (Coleus blumei) leaves ointment in wound healing of albino rats (Rattus albus). Int J Food Eng 2017; 3: 18-22
• 22 Al Mamun MA, Juyena NS, Khan MAHNA, Islam MA. Comparative effect of turmeric (Curcuma longa) and durba (Cynodon dactylon) on the healing of surgical wounds in cattle (Bos indicus). Asian J Med Biol Res 2018; 4: 164-171
• 23 Nasir MA, Mahammed NL, Roshan S, Ahmed MW. Wound healing activity of poly herbal formulation in albino rats using excision wound model, incision wound model, dead space wound model and burn wound model. Int J Res Dev Pharm L Sci 2016; 5: 2080-2087
• 24 Elzayat EM, Auda SH, Alanazi FK, Al-Agamy MH. Evaluation of wound healing activity of henna, pomegranate and myrrh herbal ointment blend. Saudi Pharm J 2018; 26: 733-738
• 25 Qureshi MS. Chemical composition and wound healing activity of methanolic leaf extract of Hydrolea zeylanica Vahl. by in vivo excision and incision models. Int J Green Pharma 2017; 11: 114-120
• 26 Balqis U, Darmawi CDI, Salim MN. Angiogenesis activity of Jatropha curcas L. latex in cream formulation on wound healing in mice. Vet World 2018; 11: 939-943
• 27 Ali MS, Rafiq M, Khasim SM. Formulation and evaluation of wound healing activity of Macroptilium atropurpureum in albino wistar rats. World J Pharmac Res 2018; 7: 582-599
• 28 Shukla R, Kashaw V. Evaluation of wound healing prospective of Momordica charantia, Pongamia glabra and Piper nigrumon anemic albino rats using incision wound model. Asian J Pharm Pharmacol 2019; 5: 401-408
• 29 Unamba-Oparah C, Unamba-Oparah IC, Eze CA, Anaga AO. Effects of the methanol leaf extract of Palisota hirsuta in post-surgical wound management. Sokoto J Vet Sci 2018; 16: 91-97
• 30 Dev SK, Choudhury PK, Srivastava R, Sharma M. Antimicrobial, anti-inflammatory and wound healing activity of polyherbal formulation. Biomed Pharmacother 2019; 111: 555-567
• 31 Sathyanarayanan S, Muniyandi K, George E, Sivaraj D, Sasidharan SP, Thangaraj P. Chemical profiling of Pterolobium hexapetalum leaves by HPLC analysis and its productive wound healing activities in rats. Biomed Pharmacother 2017; 95: 287-297
• 32 Asadi MS, Mirghazanfari SM, Dadpay M, Nassireslami E. Evaluation of wound healing activities of pomegranate (Punica granatum-Lythraceae) peel and pulp. J Res Med Dental Sci 2018; 6: 230-236
• 33 Tatke P, Nehete M, Gabhe S. Evaluation of antioxidant, antimicrobial and wound healing potential of Salvadora persica twig extracts. World J Pharm Res 2017; 6: 1186-1199
• 34 Somwanshi SB, Hiremath SN. In vivo evaluation of the wound healing activity of the Sesamum Indicum L. seed extract in novel ethosomal vesicular system. J Drug Deliv Therap 2018; 8: 411-420
• 35 Francis P, Masimba PJ, Mwakigonja AR. Evaluation of the wound healing activity of formulated ointments and water preparation from Sida rhombifolia leaf extract. Tanzania J Health Res 2018; 20: 1-8
• 36 Solanki R, Mathur V, Purohit SK, Mathur M. Evaluation of wound healing activity of ethanolic extract of Ocimum basilicum and Aegle marmelos leaves in male albino rats. Int J Drug Res Tech 2017; 2: 198-202
• 37 Rezaei M, Dadgar Z, Noori-Zadeh A, Mesbah-Namin SA, Pakzad I, Davodian E. Evaluation of the antibacterial activity of the Althaea officinalis L. leaf extract and its wound healing potency in the rat model of excision wound creation. Avicenna J Phytomed 2015; 5: 105-112
• 38 Jahandideh M, Hajimehdipoor H, Mortazavi SA, Dehpour A, Hassanzadeh G. Evaluation of the wound healing activity of a traditional compound herbal product using rat excision wound model. Iran J Pharm Res 2017; 16 (Suppl.) 153-163
• 39 Yang WT, Ke CY, Wu WT, Harn HJ, Tseng YH, Lee RP. Effects of Angelica dahurica and Rheum officinale extracts on excisional wound healing in rats. Evid Based Compl Alt Med 2017; 2017: 1583031
• 40 Miladiyah I, Prabowo BR. Ethanolic extract of Anredera cordifolia (Ten.) Steenis leaves improved wound healing in guinea pigs. Universa Med 2015; 31: 4-11
• 41 Mohsenikia M, Khakpour S, Azizian Z, Ashkani-Esfahani S, Razavipour ST, Toghiani P. Wound healing effect of Arnebia euchroma gel on excisional wounds in rats. Adv Biomed Res 2017; 6: 2
• 42 Manjula RR, Uppuluri S, Anand TJ, Adilakshmi V, Gandrapu P, Munagala A. Wound healing effect of methanolic flower extract of Bauhinia tomentosa Linn. with emu oil in rats. J Pharmacogn Phytochem 2017; 6: 247-253
• 43 Juneja K, Mishra R, Chauhan S, Gupta S, Roy P, Sircar D. Metabolite profiling and wound-healing activity of Boerhavia diffusa leaf extracts using in vitro and in vivo models. J Traditional Compl Med 2019; 10: 52-59
• 44 Azis HA, Taher M, Ahmed AS, Sulaiman WMAW, Susanti D, Chowdhury SR, Zakaria ZA. In vitro and in vivo wound healing studies of methanolic fraction of Centella asiatica extract. S Afr J Bot 2017; 108: 163-174
• 45 Vijayaraghavan K, Rajkumar J, Seyed MA. Efficacy of Chromolaena odorata leaf extracts for the healing of rat excision wounds. Vet Med 2017; 62: 565-578
• 46 Vennila V, Udayakumar R. Wound healing efficacy of herbal preparations of Croton bonplandianum Baill. on excision wound in experimental rats. Curr Trad Med 2017; 3: 38-50
• 47 Shekhar P, Joshi A, Malviya S, Kharia A. Wound healing activity of the hydro-alcoholic extract of Datura stramonium leaves in Wistar albino rats. J Drug Deliv Therap 2017; 7: 214-215
• 48 Muhamad Ibrahim A, Nagarajan A, Majeed M. Swertiamarin ointment: A traditional approach in cutaneous wound healing. Asian J Pharm Pharmacol 2019; 5: 298-309
• 49 Gorda CT, Flores AAU. Study on wound healing effect of Milk Bush (Euphorbia tirucalli Linn) in albino mice. Adv Pharm J 2018; 3: 157-161
• 50 Kang MH, Choi S, Kim BH. Skin wound healing effects and action mechanism of acai berry water extracts. Toxicol Res 2017; 33: 149-156
• 51 Goorani S, Zangeneh MM, Koohi MK, Seydi N, Zangeneh A, Souri N, Hosseini MS. Assessment of antioxidant and cutaneous wound healing effects of Falcaria vulgaris aqueous extract in Wistar male rats. Comp Clin Pathol 2019; 28: 435-445
• 52 Hanafi N, Talebpour Amiri F, Shahani S, Enayatifard R, Ghasemi M, Karimpour AA. Licorice cream promotes full-thickness wound healing in Guinea pigs. Marmara Pharm J 2018; 22: 411-421
• 53 Kotian S, Bhat K, Pai S, Nayak J, Souza A, Gourisheti K, Padma D. The role of natural medicines on wound healing: a biomechanical, histological, biochemical and molecular study. Ethiop J Health Sci 2018; 28: 759-770
• 54 Kim J, Lee CM. Wound healing potential of a polyvinyl alcohol-blended pectin hydrogel containing Hippophae rahmnoides L. extract in a rat model. Int J Biol Macromol 2017; 99: 586-593
• 55 Dons T, Soosairaj S. Evaluation of wound healing effect of herbal lotion in albino rats and its antibacterial activities. Clin Phyto Sci 2018; 4: 6
• 56 Taweepraditpol S, Chuangsuwanich A, Pradniwat K. Wound healing activity of Lawsonia inermis Linn in rat model. J Med Assoc Thai 2017; 100 (Suppl. 03) 140-144
• 57 Rafiee S, Nekouyian N, Hosseini S, Sarabandi F, Chavoshi-Nejad M, Mohsenikia M, Yadollah-Damavandi S, Seifaee S, Jangholi E, Eghtedari D, Najafi H, Ashkani-Esfahani S. Effect of topical Linum usitatissimum on full thickness excisional skin wounds. Trauma Mon 2017; 22: e64930
• 58 Shukla R, Kashaw V. Assessment of wound healing potential of Momordica charantia, Pongamia glabra and their combination with Piper nigrum on anemic albino rats using excision wound model. Asian J Pharm Pharmacol 2019; 5: 188-198
• 59 Javadi SMR, Hashemi M, Mohammadi Y, MamMohammadi A, Sharifi A, Makarchian HR. Synergistic effect of honey and Nigella sativa on wound healing in rats. Acta Cir Bras 2018; 33: 518-523
• 60 Paheerathan V, Piratheepkumar R, Kumaran K. Evaluation of wound healing activity of Nigella sativa seed powder on Wistar albino rats. Scholarly J Biol Sci 2017; 6: 60-63
• 61 Han MC, Durmus AS, Sağlıyan A, Günay C, Özkaraca M, Kandemir FM, Comakli S, Firat Oztopalan D. Effects of Nigella sativa and Hypericum perforatum on wound healing. Turk J Vet Anim Sci 2017; 41: 99-105
• 62 Kurt B, Bilge N, Sözmen M, Aydın U, Önyay T, Özaydın İ. Effects of Plantago lanceolata L. extract on full-thickness excisional wound healing in a mouse model. Biotech Histochem 2018; 93: 249-257
• 63 Kolhe SS. Evaluation of polyherbal ointment for wound healing activity in Wistar rats. J Drug Deliv Therap 2018; 8: 26-31
• 64 Alshammari ND, Fatima N, Nayeem N. Punica granatum rind, a traditional herbal medicine: effect on wound healing. Int J Pharm Res Allied Sci 2017; 6: 53-58
• 65 Handoo N, Parrah JD, Athar H, Abrar Gayas M, Imtiyaz T, Bisma S. Wound healing and anti-bacterial efficacy of Rheum emodi and its different extracts on excisional wounds in rabbits. J Entomol Zoology Stud 2018; 6: 1204-1213
• 66 Lei Z, Cao Z, Yang Z, Ao M, Jin W, Yu L. Rosehip oil promotes excisional wound healing by accelerating the phenotypic transition of macrophages. Planta Med 2018; 85: 563-569
• 67 Sakeena Q, Ansari MM, Sakeena S, Muzamil S, Makhdoomi DM. In vivo assessment of lipid peroxidation and antioxidant profile in aqueous and ethanolic extract ointment of Salix acmophylla leaves in rabbits for wound healing improvement on excisional full thickness skin wounds. Pharma Innovat J 2018; 7: 492-500
• 68 Fatima N, Iqbal W, Yaqeen SS. Evaluation of wound healing effects between Salvadora persica ointment and Solcoseryl jelly in animal model. Pak J Pharm Sci 2015; 28: 1777-1780
• 69 Ghabaee DNZ, Ebrahimzadeh MA, Akbari J, Amiri FT. Wound healing activity of Sambucus ebulus . Int J Pharm Sci Res 2017; 8: 132-135
• 70 Beyranvand F, Gharzi A, Abbaszadeh A, Khorramabadi RM, Gholami M, Gharravi AM. Encapsulation of Satureja khuzistanica extract in alginate hydrogel accelerate wound healing in adult male rats. Inflam Reg 2019; 39: 2
• 71 Estevão LRM, Simões RS, Cassini-Vieira P, Canesso MCC, Barcelos LDS, Rachid MA, Câmara CAGD, Evêncio-Neto J. Schinus terebinthifolius Raddi (Aroeira) leaves oil attenuates inflammatory responses in cutaneous wound healing in mice. Acta Cir Bras 2017; 32: 726-735
• 72 Ghashghaii A, Hashemnia M, Nikousefat Z, Zangeneh MM, Zangeneh A. Wound healing potential of methanolic extract of Scrophularia striata in rats. Pharm Sci 2017; 23: 256-263
• 73 Goorani S, Zangeneh MM, Zangeneh A, Poorshamohammad C, Abiari M, Moradi R, Najafi F, Tahvilian R. Study of wound healing potential of Stevia rebaudiana ethanol extract in male rats. Res J Pharmacogn 2018; 5: 23-30
• 74 Talekar YP, Apte KG, Paygude SV, Tondare PR, Parab PB. Studies on wound healing potential of polyherbal formulation using in vitro and in vivo assays. J Ayurveda Integ Med 2017; 8: 73-81
• 75 Babaei E, Asghari MH, Mehdikhani F, Moloudizargari M, Ghobadi E, Pouya SRH. The healing effects of herbal preparations from Sambucus ebulus and Urtica dioica in full-thickness wound models. Asian Pac J Trop Biomed 2017; 7: 421-427
• 76 Hamid A, Lian CP, Hudin NHS, Ghazali AR, Jufri NF. Zingiber zerumbet rhizomes extract exhibits faster open wound healing in rats. Pharmacog Res 2018; 10: 354-360
• 77 Verma RK, Pandey M, Indoria MD, Singh R, Suthar S. Phytochemical investigation and pharmacological evaluation of leaves of Ziziphus mauritiana for wound healing activity in albino rats. Trop J Pharm Life Sci 2018; 5: 8-18
• 78 Lodhi S, Jain A, Jain AP, Pawar RS, Singhai AK. Effects of flavonoids from Martynia annua and Tephrosia purpurea on cutaneous wound healing. Avicenna J Phytomed 2016; 6: 578-591
• 79 Hajhashemi M, Ghanbari Z, Movahedi M, Rafieian M, Keivani A, Haghollahi F. The effect of Achillea millefolium and Hypericum perforatum ointments on episiotomy wound healing in primiparous women. J Matern Fetal Neonatal Med 2018; 31: 63-69
• 80 Molazem Z, Mohseni F, Younesi M, Keshavarzi S. Aloe vera gel and cesarean wound healing; a randomized controlled clinical trial. Glob J Health Sci 2015; 7: 203-209
• 81 Jahdi F, Khabbaz AH, Kashian M, Taghizadeh M, Haghani H. The impact of calendula ointment on cesarean wound healing: a randomized controlled clinical trial. J Family Med Prim Care 2018; 7: 893-897
• 82 Hemmati AA. The topical effect of grape seed extract 2 % cream on surgery wound healing. Glob J Health Sci 2015; 7: 52-58
• 83 Shahrahmani H, Kariman N, Jannesari S, Rafieian-Kopaei M, Mirzaei M, Ghalandari. Shahrahmani N, Mardani G. The effect of green tea ointment on episiotomy pain and wound healing in primiparous women: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res 2018; 32: 522-530
• 84 Negut I, Grumezescu V, Grumezescu A. Treatment strategies for infected wounds. Molecules 2018; 23: 2392
• 85 Rodero MP, Khosrotehrani K. Skin wound healing modulation by macrophages. Int J Clin Exp Pathol 2010; 3: 643-653
• 86 Hesketh M, Sahin KB, West ZE, Murray RZ. Macrophage phenotypes regulate scar formation and chronic wound healing. Int J Mol Sci 2017; 18: 1545
• 87 Koh TJ, DiPietro LA. Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med 2011; 13: e23
• 88 Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci 2016; 73: 3861-3885
• 89 Knapinska A, Fields GB. Chemical biology for understanding matrix metalloproteinase function. Chembiochem 2012; 13: 2002-2020
• 90 Beanes SR, Dang C, Soo C, Ting K. Skin repair and scar formation: the central role of TGF-β . Exp Rev Mol Med 2003; 5: 1-22
• 91 Shah M, Foreman DM, Ferguson MW. Neutralization of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci 1995; 108: 985-1002
• 92 Schafer M, Werner S. Oxidative stress in normal and impaired wound repair. Pharmacol Res 2008; 58: 165-171
• 93 Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, Leaper D, Georgopoulos NT. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J 2017; 14: 89-96
• 94 Kurahashi T, Fujii J. Roles of antioxidative enzymes in wound healing. J Develop Biol 2015; 3: 57-70
• 95 De Smet PA. Health risks of herbal remedies: an update. Clin Pharmacol Ther 2004; 76: 1-17