Wound Healing with Botanicals: a Review and Future Perspectives
Purpose of Review
Botanicals have long played a crucial role in the management of chronic and infected wounds, yet the mechanistic basis of these therapies remains largely poorly understood by modern science.
Studies have begun to unveil the mechanistic bases of botanical therapies for wound healing, but more work is necessary. Most notably, investigation into the growing conditions, post-harvest treatment, and pharmacological preparation of these botanicals has demonstrated their importance in terms of the chemical makeup and pharmacological activity of the final product used in pre-clinical and clinical studies.
This work evaluates the potential safety, efficacy, and mechanistic basis of some key botanical ingredients used in traditional medicine for wound care: aloe, marigold, and St. John’s Wort. Furthermore, perspectives on the future role that botanical natural products may play in anti-infective and wound care, innovations are explored.
KeywordsWounds Botanicals Wound healing Medicinal plants Complementary medicine Infection
Work in the Quave Research Group is funded by the National Institutes of Health, National Institute of Allergy and Infectious Disease (R21 AI136563, PI: CLQ). The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The author is an inventor on patents concerning botanical inhibitors of microbial biofilm formation and quorum sensing; the author confirms that any competing interests do not alter her adherence to journal policies on ethics and sharing data or materials. The author provided consulting services to Medline during the period of writing this study. The author declares that provision of these services did not have any impact on the present study.
Dr. Quave reports grants from National Institutes of Health, National Institute of Allergy and Infectious Disease, from null, during the conduct of the study; personal fees from Medline, from null, outside the submitted work. In addition, Dr. Quave has a patent Quave, C.L., M.S. Smeltzer, C.M. Compadre, H. Hendrickson. Anti-biofilm compositions and methods for using Patent Numbers: WO2012048119-A2; US2012088671-A1; WO2012048119-A3. Derwent Primary Accession No.: 2012-E22562; Issued June 3, 2014; US 9,351,492 B2 Issued May 31, 2016 issued, a patent Quave, C.L., A.R. Horswill, J.T. Lyles. Botanical extracts and compounds from Castanea plants and methods of use. Provisional Filed June 26, 2015. Serial No. 62/185,146. Non-Provisional Filed June 24, 2016 Serial No. 15/195,514 pending, and a patent Quave, C.L. and J.T. Lyles. Botanical extracts and compounds from Schinus plants and methods of use. Provisional filed July 10, 2015; serial no. 62/190,802; non-provisional filed July 8, 2016; serial no. 15/205,493, pending.
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH or NIAID.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Willis KJ. State of the World’s plants report. London, England: Royal Botanic Gardens, Kew; 2017.Google Scholar
- 3.The Plant List Version 1.1. Published on the Internet. 2013. http://www.theplantlist.org/. Accessed September 9 2018.
- 4.Stevens PF. Angiosperm Phylogeny Website, version 14. 2001 Onwards. http://www.mobot.org/MOBOT/research/APweb/. Accessed September 10 2018.
- 5.Carter S, Newton LE, Lavranos JJ, Walker CC. Aloes: the definitive guide. London: Royal Botanic Gardens, Kew; 2011.Google Scholar
- 6.Ross IA. Medicinal plants of the world: chemical constituents, traditional, and modern medicinal uses. Humana Press; 1999.Google Scholar
- 10.•• Minjares-Fuentes R, Femenia A, Comas-Serra F, Rodríguez-González VM. Compositional and structural features of the main bioactive polysaccharides present in the Aloe vera plant. J AOAC Int. 2018;101. Doi: https://doi.org/10.5740/jaoacint.18-0119. This study examines the variability in compositional features of Aloe vera gel and provides a chemical explanation for differences in the pharmacology of aloe shown in the literature. CrossRefGoogle Scholar
- 11.Teplicki E, Ma Q, Castillo DE, Zarei M, Hustad AP, Chen J, et al. The effects of Aloe vera on wound healing in cell proliferation, migration, and viability. Wounds. 2018;30(9):263–8.Google Scholar
- 14.• Sari Y, Purnawan I, Kurniawan DW, Sutrisna E. A comparative study of the effects of Nigella sativa oil gel and Aloe vera gel on wound healing in diabetic rRats. J Evidence-based Integr Med. 2018;23:2515690X18772804. https://doi.org/10.1177/2515690X18772804 This study examines two popular traditional medicines for wound care and offers comparative insight into the efficacy of Aloe vera over that of another botanical. CrossRefGoogle Scholar
- 16.• Woeller Collynn F, Woodroof A, Cottler Patrick S, Pollock Stephen J, Haidaris Constantine G, Phipps RP. In vitro characterization of variable porosity wound dressing with anti-scar properties. Eplasty. 2018;18:e21 This study offers an interesting perspective on the incorporation of botanicals into medical devices for the promotion of wound healing. PubMedPubMedCentralGoogle Scholar
- 18.Dat AD, Poon F, Pham KBT, Doust J. Aloe vera for treating acute and chronic wounds. Cochrane Database Syst Rev 2012(2). doi: https://doi.org/10.1002/14651858.CD008762.pub2.
- 22.Basch E, Bent S, Foppa I, Haskmi S, Kroll D, Mele M, et al. Marigold (Calendula officinalis L.): an evidence-based systematic review by the natural standard research collaboration. J Herb Pharmacother. 2006;6(3/4):135–59. https://doi.org/10.1300/J157v06n03-08.
- 23.Khalid KA, da Silva JAT. Biology of Calendula officinalis Linn.: focus on pharmacology, biological activities and agronomic practices. Medicinal and Aromatic Plant Sci Biotechnol. 2012;6(1):12–27.Google Scholar
- 26.• Jarić S, Kostić O, Mataruga Z, Pavlović D, Pavlović M, Mitrović M, et al. Traditional wound-healing plants used in the Balkan region (Southeast Europe). J Ethnopharmacol. 2018;211:311–28. https://doi.org/10.1016/j.jep.2017.09.018 This is a literature review of 128 plant species used in traditional remedies for wound healing in the Balkans. It highlights the medicinal applications of Calendula officinalis and Hypericum perforatum for these purposes. CrossRefPubMedGoogle Scholar
- 31.Muley B, Khadabadi S, Banarase N. Phytochemical constituents and pharmacological activities of Calendula officinalis Linn (Asteraceae): a review. Tropical J Pharmaceutical Res. 2009;8(5).Google Scholar
- 32.Zitterl-Eglseer K, Sosa S, Jurenitsch J, Schubert-Zsilavecz M, Della Loggia R, Tubaro A, et al. Anti-oedematous activities of the main triterpendiol esters of marigold (Calendula officinalis L.). J Ethnopharmacol. 1997;57(2):139–44. https://doi.org/10.1016/S0378-8741(97)00061-5.CrossRefPubMedGoogle Scholar
- 35.Efstratiou E, Hussain AI, Nigam PS, Moore JE, Ayub MA, Rao JR. Antimicrobial activity of Calendula officinalis petal extracts against fungi, as well as Gram-negative and Gram-positive clinical pathogens. Complement Ther Clin Pract. 2012;18(3):173–6. https://doi.org/10.1016/j.ctcp.2012.02.003.CrossRefPubMedGoogle Scholar
- 36.•• Nicolaus C, Junghanns S, Hartmann A, Murillo R, Ganzera M, Merfort I. In vitro studies to evaluate the wound healing properties of Calendula officinalis extracts. J Ethnopharmacol. 2017;196:94–103. https://doi.org/10.1016/j.jep.2016.12.006 This study provides details on a useful model for in vitro evaluation of botanical extracts for potential mechanisms of wound healing. CrossRefPubMedGoogle Scholar
- 37.•• Buzzi M, de Freitas F, Winter M. A prospective, descriptive study to assess the clinical benefits of using Calendula officinalis hydroglycolic extract for the topical treatment of diabetic foot ulcers. Ostomy Wound Manage. 2016;62(3):8–24 This study demonstrates promising data on the topical spray application of C. officinalis extracts in diabetic foot ulcers. In addition to observations of wound closure in many patients, there was also a reduction in odorous wounds. PubMedGoogle Scholar
- 38.Panahi Y, Sharif MR, Sharif A, Beiraghdar F, Zahiri Z, Amirchoopani G, et al. A randomized comparative trial on the therapeutic efficacy of topical Aloe vera and Calendula officinalis on diaper dermatitis in children. Sci World J. 2012;2012:810234–5. https://doi.org/10.1100/2012/810234.Google Scholar
- 39.Bolderston A, Lloyd NS, Wong RKS, Holden L, Robb-Blenderman L. Supportive Care Guidelines Group of Cancer Care Ontario Program in Evidence-based Care. The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline. Support Care Cancer. 2006;14(8):802. https://doi.org/10.1007/s00520-006-0063-4.CrossRefPubMedGoogle Scholar
- 40.HMPC. Community Herbal Monograpg on Calendula officinalis L., flos. Committee on Herbal Medicinal Products (HMPC), European Medicines Agency. 2008.Google Scholar
- 41.Reider N, Komericki P, Hausen BM, Fritsch P, Aberer W. The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.). Contact Dermatitis. 2001;45(5):269–72. https://doi.org/10.1034/j.1600-0536.2001.450503.x.CrossRefPubMedGoogle Scholar
- 45.Redžić SS. The ecological aspect of ethnobotany and ethnopharmacology of population in Bosnia and Herzegovina. Collegium Antropologicum. 2007;3:869–90.Google Scholar
- 50.Hölzl J, Petersen M. Chemical constituents of Hypericum species. In: Ernst E, editor. Hypericum: the genus Hypericum. New York: Taylor & Francis; 2003. p. 77–93.Google Scholar
- 53.•• Lyles JT, Kim A, Nelson K, Bullard-Roberts AL, Hajdari A, Mustafa B, et al. The chemical and antibacterial evaluation of St. John’s Wort oil macerates used in Kosovar traditional medicine. Front Microbiol. 2017;8:1639. https://doi.org/10.3389/fmicb.2017.01639 This study provides a detailed look at the differences in the chemical makeup and biological activity of St. John’s Wort extracts, highlighting the important role that extraction methodologies can have on study outcomes. CrossRefPubMedPubMedCentralGoogle Scholar
- 54.Gunpinar S, Kilic OA, Duran I, Tosun M, Firat T, Soyler G. Evaluation of the effect of topical Hypericum perforatum oil on excisional palatal wound healing in rabbits. J Investig Surg. 2018:1–10. https://doi.org/10.1080/08941939.2018.1474980.
- 56.• Güneş S, Tıhmınlıoğlu F. Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material. Int J Biol Macromol. 2017;102:933–43. https://doi.org/10.1016/j.ijbiomac.2017.04.080 This study demonstrates how botanical ingredients can be incorporated into wound dressings and evaluated both for antimicrobial and human cytotoxicity in vitro. CrossRefPubMedGoogle Scholar
- 59.Schempp CM, Winghofer B, Lüdtke R, Simon-Haarhaus B, Schöpf E, Simon JC. Topical application of St John’s wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Br J Dermatol. 2002;142(5):979–84. https://doi.org/10.1046/j.1365-2133.2000.03482.x.CrossRefGoogle Scholar
- 60.Lavagna SM, Secci D, Chimenti P, Bonsignore L, Ottaviani A, Bizzarri B. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section Il. Farmaco. 2001;56(5):451–3. https://doi.org/10.1016/S0014-827X(01)01060-6.CrossRefPubMedGoogle Scholar