Abstract
The multi-drug resistant Staph. aureus strain, Methicillin-resistant Staphylococcus aureus (MRSA), is an emerging pathogen that could penetrate skin cuts and wounds, causing a life-threatening condition. The green biosynthesis of silver nanoparticles with liquorice extract has been demonstrated over several years for anticancer and antioxidant effects, as well as antibacterial effect against both Gram-positive and Gram-negative bacteria. The study was designed to evaluate the synergistic in vivo and in vitro wound healing and anti-MRSA activity of decorated liquorice silver nanoparticles (LD-AgNPs). The LD-AgNPs were prepared by thoroughly mixing diluted liquorice extract with AgNO3 at room temperature. The prepared nanoparticles were characterized by size measurement, IR spectroscopy, TEM imaging, and X-ray diffraction. The in vitro and in vivo antibacterial and wound healing testing were also performed. The obtained LD-AgNPs were spherical in shape and had a hydrodynamic size of about 50.16 ± 5.37 nm. Moreover, they showed potent antibacterial activity against Gram-positive and Gram-negative resistant bacteria, produced a significantly higher level of procollagen type I compared to either liquorice extract or standard silver sulfadiazine, and promoted the wound healing process in rabbits. The formulation of silver nanoparticles with liquorice extract showed synergetic effects in enhancing the treatment of wounds, with significant antibacterial activity against E. coli and MRSA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout






References
Mohammed HA, et al. Bio-evaluation of the wound healing activity of Artemisia judaica L. as part of the plant’s use in traditional medicine; Phytochemical, antioxidant, anti-inflammatory, and antibiofilm properties of the plant’s essential oils. Antioxidants. 2022;11:332.
Longaker MT, et al. Adult skin wounds in the fetal environment heal with scar formation. Ann Surg. 1994;219:65.
Tuhin RH, et al. Wound healing effect of Euphorbia hirta linn.(Euphorbiaceae) in alloxan induced diabetic rats. BMC Complement Altern Med. 2017;17:1–14.
Alminderej F, et al. Antimicrobial and wound healing potential of a new chemotype from Piper cubeba L. essential oil and in silico study on S. aureus tyrosyl-tRNA synthetase protein. Plants. 2021;10:205.
Mohammed HA, Mohammed SAA, Khan O, Ali HM. Topical eucalyptol ointment accelerates wound healing and exerts antioxidant and anti-inflammatory effects in rats’ skin burn model. J Oleo Sci. 2022;71:1777–88.
Qureshi KA, et al. Cinnamaldehyde-based self-nanoemulsion (CA-SNEDDS) accelerates wound healing and exerts antimicrobial, antioxidant, and anti-inflammatory effects in rats’ skin burn model. Molecules. 2022;27:5225.
Song K, Yan M, Li M, Geng Y, Wu X. Preparation and in vitro–in vivo evaluation of novel ocular nanomicelle formulation of thymol based on glycyrrhizin. Colloids Surf B Biointerfaces. 2020;194:111157.
Mamedov NA, Egamberdieva D. Phytochemical constituents and pharmacological effects of licorice: a review. Plant Hum Heal. 2019;3:1–21.
Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MBPP. Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phyther Res. 2018;32:2323–39.
Assar DH, et al. Wound healing potential of licorice extract in rat model: Antioxidants, histopathological, immunohistochemical and gene expression evidences. Biomed Pharmacother. 2021;143:112151.
Tanideh N, et al. The healing effect of licorice on Pseudomonas aeruginosa infected burn wounds in experimental rat model. World J Plast Surg. 2014;3:99.
Sidhu P, et al. Therapeutic benefits of liquorice in dentistry. J Ayurveda Integr Med. 2020;11:82–88.
Ibraheem DR, et al. Ciprofloxacin-loaded silver nanoparticles as potent nano-antibiotics against resistant pathogenic bacteria. Nanomaterials. 2022;12:2808.
Abdul-Jabbar AM, et al. Combined anti-bacterial actions of lincomycin and freshly prepared silver nanoparticles: overcoming the resistance to antibiotics and enhancement of the bioactivity. Antibiotics. 2022;11:1791.
Khane Y, et al. Green synthesis of silver nanoparticles using aqueous Citrus limon zest extract: Characterization and evaluation of their antioxidant and antimicrobial properties. Nanomaterials. 2022;12:2013.
Saddik MS, et al. Biosynthesis, characterization, and wound-healing activity of phenytoin-loaded copper nanoparticles. AAPS PharmSciTech. 2020;21:1–12.
Xu L, et al. Silver nanoparticles: Synthesis, medical applications and biosafety. Theranostics. 2020;10:8996.
Mori Y, et al. Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virus. Nanoscale Res Lett. 2013;8:1–6.
Keleştemur S, et al. Wound healing properties of modified silver nanoparticles and their distribution in mouse organs after topical application. Nano Biomed Eng. 2012;4:170.
Maksoud HAA, et al. Ameliorative effect of liquorice extract versus silymarin in experimentally induced chronic hepatitis: A biochemical and genetical study. Clin Nutr Exp. 2019;23:69–79.
Erdogan O, et al. Green synthesis of silver nanoparticles via Cynara scolymus leaf extracts: The characterization, anticancer potential with photodynamic therapy in MCF7 cells. PLoS One. 2019;14:e0216496.
Lee AS, et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Prim. 2018;4:1–23.
El-Feky GS, Zayed GM. PLGA nanoparticles loaded mucoadhesive and thermosensitive hydrogel as a potential platform for the treatment of oral mucositis. Int J Appl Pharm. 2019;11:106–12.
Sreelakshmy V, Deepa MK, Mridula P. Green synthesis of silver nanoparticles from Glycyrrhiza glabra root extract for the treatment of gastric ulcer. J Dev Drugs. 2016;5:2.
Albukhaty S, et al. Investigation of dextran-coated superparamagnetic nanoparticles for targeted vinblastine controlled release, delivery, apoptosis induction, and gene expression in pancreatic cancer cells. Molecules. 2020;25:4721.
Al Rugaie O, et al. Modification of SWCNTs with hybrid materials ZnO–Ag and ZnO–Au for enhancing bactericidal activity of phagocytic cells against Escherichia coli through NOX2 pathway. Sci Rep. 2022;12:1–12.
Qais FA, et al. Antibacterial effect of silver nanoparticles synthesized using Murraya koenigii (L.) against multidrug-resistant pathogens. Bioinorg Chem Appl. 2019;2019:1–12.
Diniz FR, et al. Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo. Nanomaterials. 2020;10:390.
Mekkawy AI, et al. In vitro and in vivo evaluation of biologically synthesized silver nanoparticles for topical applications: effect of surface coating and loading into hydrogels. Int J Nanomed. 2017;12:759.
Abdel-Maguid EM, et al. Efficacy of stem cell-conditioned medium vs. platelet-rich plasma as an adjuvant to ablative fractional CO2 laser resurfacing for atrophic post-acne scars: a split-face clinical trial. J Dermatol Treat. 2021;32:242–9.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25:402–8.
Kumar B, Vijayakumar M, Govindarajan R, Pushpangadan P. Ethnopharmacological approaches to wound healing—exploring medicinal plants of India. J Ethnopharmacol. 2007;114:103–13.
Jang MH, Piao XL, Kim JM, Kwon SW, Park JH. Inhibition of cholinesterase and amyloid-&bgr; aggregation by resveratrol oligomers from Vitis amurensis. Phyther Res [Internet]. 2008;22:544–9.
Carswell EA, et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 1975;72:3666–70.
Sokol CL, Barton GM, Farr AG, Medzhitov R. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol. 2008;9:310–8.
Chornenka NM, et al. Correction parameters of endogenous intoxication in experimental burn disease at the stage of toxemia. Res J Pharm Biol Chem Sci. 2016;7:1042–7.
Raetska Y, et al. Cytokine profile indicators in rat blood serum in a model of esophagus burn induced by antioxidant chemical preparation. Biomed Res Ther. 2017;4:1591–606.
Rodríguez-Luis O, et al. Green synthesis of silver nanoparticles and their bactericidal and antimycotic activities against oral microbes. J Nanomater. 2016;2016:1–10.
Gupta Y, Sharma V, Kumar BVM. Issues in determining size of nano-crystalline ceramic particles by X-ray diffraction. Mater Today Proc. 2015;2:3534–8.
Durán N, et al. Silver nanoparticles: A new view on mechanistic aspects on antimicrobial activity. Nanomed Nanotechnol, Biol Med. 2016;12:789–99.
Vazquez-Muñoz R, et al. Enhancement of antibiotics antimicrobial activity due to the silver nanoparticles impact on the cell membrane. PLoS One. 2019;14:e0224904.
Li Q, et al. Antimicrobial nanomaterials for water disinfection and microbial control: potential applications and implications. Water Res. 2008;42:4591–602.
Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015;5:310–5.
Long DR, Mead J, Hendricks JM, Hardy ME, Voyich JM. 18β-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrob Agents Chemother. 2013;57:241–7.
Ahmeda A, Zangeneh A, Zangeneh MM. Characterization and anti‐acute T cell leukemia properties of silver nanoparticles synthesized by a green approach for bioremediation applications: Introducing a new chemotherapeutic drug for clinical trial studies. Appl Organomet Chem. 2020;34:e5374.
Kędzierska M, et al. Silver nanoparticles and glycyrrhiza glabra (Licorice) root extract as modifying agents of hydrogels designed as innovative dressings. Int J Mol Sci. 2022;24:1–23.
Feng D, Zhang R, Zhang M, Fang A, Shi F. Synthesis of eco-friendly silver nanoparticles using glycyrrhizin and evaluation of their antibacterial ability. Nanomaterials. 2022;12:2636.
Mishra RC, Kumari R, Iqbal Z, Rizvi MMA, Yadav JP. Synthesis, characterization, comparative antidandruff efficacy and cytotoxicity studies of biosynthesized silver nanoparticles by using Glycyrrhiza glabra root. Adv Sci Eng Med. 2020;12:156–62.
Mathew-Steiner SS, Roy S, Sen CK. Collagen in wound healing. Bioengineering (Basel). 2021;8:1–15.
Chowdhury S, et al. Influence of silver nanoparticles on post-surgical wound healing following topical application. Eur J Nanomed. 2014;6:237–47.
Ritsu M, et al. Critical role of tumor necrosis factor-α in the early process of wound healing in skin. J Dermatol Dermatologic Surg. 2016;21:14–9.
Sindagikar V, Narasanagi B, Ragate A, Patel F. Effect of serum albumin in wound healing and its related complications in surgical patients. Al ameen J Med Sci. 2017;1:132–5.
Majhi D. Hypoalbuminemia is an important risk factor for surgical wound healing. J Med Sci Clin Res. 2019;7:921–5.
Nosenko M, Ambaryan S, Drutskaya M. Proinflammatory cytokines and skin wound healing in mice. Mol Biol. 2019;53:653–64.
Xiao T, Yan Z, Xiao S, Xia Y. Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization. Stem Cell Res Ther. 2020;11:1–9.
Acknowledgements
The authors would like to thank the institutional support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Mohammed, H.A., Amin, M.A., Zayed, G. et al. In vitro and in vivo synergistic wound healing and anti-methicillin-resistant Staphylococcus aureus (MRSA) evaluation of liquorice-decorated silver nanoparticles. J Antibiot (2023). https://doi.org/10.1038/s41429-023-00603-4
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41429-023-00603-4