An assessment of the evidence for antibacterial activity of stinging nettle (Urtica dioica) extracts

Stinging nettles (Urtica spp.) have been used in a diverse range of traditional and historical medicines from around the world for the treatment of skin diseases, wounds, urinary disorders, respiratory diseases, bone and joint pain, anaemia and other circulatory problems, as well as in cosmetic preparations for skin and haircare. As part of an interdisciplinary exploration of nettle-based remedies, we performed a systematic review of published evidence for the antimicrobial activity of Urtica spp. extracts against bacteria and fungi that commonly cause skin, soft tissue and respiratory infections. We focussed on studies in which minimum inhibitory concentration (MIC) assays of U. dioica were conducted on the common bacterial opportunistic pathogens Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus. No studies used fresh leaves (all were dried prior to use), and no studies prepared nettles in weak acid (corresponding to vinegar) or in fats/oils, which are common combinations in historical and traditional preparations. We addressed this gap by conducting new antibacterial tests of extracts of fresh U. dioica leaves prepared in vinegar, butter or olive oil against P. aeruginosa and S. aureus. Our systematic review and additional experimental data leads us to conclude that there is no strong evidence for nettles containing molecules with clinically useful antimicrobial activity. It seems most likely that the utility of nettles in traditional topical preparations for wounds may simply be as a ‘safe’ absorbent medium for keeping antibacterial (vinegar) or emollient (oils) ingredients at the treatment site

A case study of the Ancientbiotics collaboration

Collaborations that cross traditional boundaries between disciplines in STEM and the arts and humanities open up exciting research possibilities. In our team’s case, we combined expertise in historical manuscripts, data science, and microbiology to explore the structure and potential efficacy of historical medical recipes. Such an approach can highlight patterns or questions that a single-disciplinary approach is likely to miss. But learning to speak each other’s disciplinary languages is not always easy, and misunderstandings can impede work. Here, we present our own experiences as a case study of how we have learned from each other to ask new questions of our source material and the problems we have had to solve along the way

Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients

Novel antimicrobials are urgently needed to combat drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. Studying plants and other natural materials used in historical infection remedies may enable further discoveries to help fill the antibiotic discovery gap. We previously reconstructed a 1,000-year-old remedy containing onion, garlic, wine, and bile salts, known as ‘Bald’s eyesalve’, and showed it had promising antibacterial activity. In this current paper, we have found this bactericidal activity extends to a range of Gram-negative and Gram-positive wound pathogens in planktonic culture and, crucially, that this activity is maintained against Acinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes in a soft-tissue wound biofilm model. While the presence of garlic in the mixture can explain the activity against planktonic cultures, garlic has no activity against biofilms. We have found the potent anti-biofilm activity of Bald’s eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity. Our work highlights the need to explore not only single compounds but also mixtures of natural products for treating biofilm infections and underlines the importance of working with biofilm models when exploring natural products for the anti-biofilm pipeline

Biguanide iridium(III) complexes with potent antimicrobial activity

We have synthesized novel organoiridium(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus (MRSA)) and high antifungal potency toward C. albicans and C. neoformans, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant Enterococci (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone

The safety profile of Bald’s eyesalve for the treatment of bacterial infections

Abstract: The rise in antimicrobial resistance has prompted the development of alternatives to combat bacterial infections. Bald’s eyesalve, a remedy used in the Early Medieval period, has previously been shown to have efficacy against Staphylococcus aureus in in vitro and in vivo models of chronic wounds. However, the safety profile of Bald’s eyesalve has not yet been demonstrated, and this is vital before testing in humans. Here, we determined the safety potential of Bald’s eyesalve using in vitro, ex vivo, and in vivo models representative of skin or eye infections. We also confirmed that Bald’s eyesalve is active against an important eye pathogen, Neisseria gonorrhoeae. Low levels of cytotoxicity were observed in eyesalve-treated cell lines representative of skin and immune cells. Results from a bovine corneal opacity and permeability test demonstrated slight irritation to the cornea that resolved within 10 min. The slug mucosal irritation assay revealed that a low level of mucus was secreted by slugs indicating moderate mucosal irritation. We obtained promising results from mouse wound closure experiments; no visible signs of irritation or inflammation were observed. Our results suggest that Bald’s eyesalve could be tested further on human volunteers to assess safety for topical application against bacterial infections

An interdisciplinary investigation into the antibacterial activity and chemical composition of the historical remedy Bald's eyesalve

The golden age of antibiotic discovery has granted us a respite from incurable infections. However, bacteria can become tolerant to antibiotics by forming biofilms, and they can evolve resistance to antibiotics, rendering them useless. Finding new antibiotics is difficult, but looking into historical medicine may provide some answers. This PhD project has conducted an interdisciplinary investigation into a 10th-century remedy, Bald's eyesalve. This remedy calls for crushed onion and garlic to be combined with wine and ox gall, and left to stand for 9 days. This remedy was previously shown to have potent activity against S. aureus. Here, I have identified that many steps in the recipe create a more active remedy, highlighting the potential scholar behind these texts. I demonstrate this activity extends to a broad range of planktonic cultures (S. aureus, including MRSA, A. baumannii (including multi-drug resistant strains), E. coli, P. aeruginosa, B. cenocepa- cia). Importantly, a subset of these strains grown as established biofilms in a synthetic wound model were also eradicated (S. au- reus, all A. baumannii and B. cenocepacia). A. baumannii was unable to develop resistance to the remedy, but became resistant to antibiotics (meropenem and ciprooxacin) within 35 days. Chemical analysis (HPLC) has identified that although allicin is responsible for the activity against planktonic cultures, it was significantly less active against biofilms than Bald's eyesalve. Further analysis (LC-MS/MS) identified a combination of allicin with an aqueous wine fraction work synergistically to eradicate these S. aureus biofilms. To conclude, a potent antimicrobial semi-synthetic cocktail containing allicin and aqueous wine components has been developed from the historical remedy Bald's eyesalve. Additionally, these results stress the importance of 1) including biofilm models when exploring natural products for the anti-biofilm pipeline; and 2) researching mixtures of natural products, rather than isolated compounds, may generate potent therapies

Biguanide Iridium(III) Complexes with Potent Antimicrobial Activity

We have synthesized novel organoiridium­(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)) and high antifungal potency toward <i>C. albicans</i> and <i>C. neoformans</i>, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant <i>Enterococci</i> (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone

Biguanide Iridium(III) Complexes with Potent Antimicrobial Activity

We have synthesized novel organoiridium­(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)) and high antifungal potency toward <i>C. albicans</i> and <i>C. neoformans</i>, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant <i>Enterococci</i> (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone

Biguanide Iridium(III) Complexes with Potent Antimicrobial Activity

We have synthesized novel organoiridium­(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)) and high antifungal potency toward <i>C. albicans</i> and <i>C. neoformans</i>, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant <i>Enterococci</i> (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone

Biguanide Iridium(III) Complexes with Potent Antimicrobial Activity

We have synthesized novel organoiridium­(III) antimicrobial complexes containing a chelated biguanide, including the antidiabetic drug metformin. These 16- and 18-electron complexes were characterized by NMR, ESI-MS, elemental analysis, and X-ray crystallography. Several of these complexes exhibit potent activity against Gram-negative bacteria and Gram-positive bacteria (including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)) and high antifungal potency toward <i>C. albicans</i> and <i>C. neoformans</i>, with minimum inhibitory concentrations (MICs) in the nanomolar range. Importantly, the complexes exhibit low cytotoxicity toward mammalian cells, indicating high selectivity. They are highly stable in broth medium, with a low tendency to generate resistance mutations. On coadministration, they can restore the activity of vancomycin against vancomycin-resistant <i>Enterococci</i> (VRE). Also the complexes can disrupt and eradicate bacteria in mature biofilms. Investigations of reactions with biomolecules suggest that these organometallic complexes deliver active biguanides into microorganisms, whereas the biguanides themselves are inactive when administered alone