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.

Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers

“…A test in healthy participants is a necessary prerequisite before testing the salve with a hospitalised or community-based sample of patients with chronic wounds. Taken together with our published observation that the salve did not interfere with normal healing in experimentally wounded mice 28 , our results provide some justification for a future trial with a participant group who better reflect the age and health profile of people at risk of chronic wounds. A future trial should test the salve using a surgical dressing or advanced wound care dressing with known tolerability e.g.…”

“…We investigated the safety profile of a medieval “ancientbiotic”, a preparation of four natural ingredients which we found to have excellent antibacterial and antibiofilm activity in laboratory and animal models. Our previous work suggested a promising safety profile in an ex vivo model of eye irritation and a mouse model of wound healing 26 – 28 . This trial represents the first topical application of our reconstructed remedy to human participants.…”

“…A fresh batch of Bald’s eyesalve was prepared following our published protocol 26 – 28 . We used garlic and onions sourced from a commercial greengrocer, Pennard Organic white wine (11% ABV; Avalon Vineyard, Somerset), and dried bovine bile (Merck Millipore catalogue no.…”

“…the combination and preparation of ingredients generates a cocktail of compounds and/or a novel compound which effectively kills bacteria. A recent study from our laboratory showed that Bald’s eyesalve possess a promising safety profile in vitro, in an ex vivo model of eye irritation, and in a mouse model of chronic wound healing 28 . Garlic can cause severe irritation and burns when applied to skin 29 , but our mouse experiments suggested that this effect may be ameliorated when garlic is prepared along with other ingredients, following the medieval eyesalve instructions.…”

A case study of the Ancientbiotics collaboration

“…We sought to understand if the preparation steps used in historical remedies that have some biological activity form an essential prerequisite to finding natural products with clinical potential. This aim depends on the recognition that, in previous studies of natural product potential, following historical recipe instructions has proved critical in observing successful activity (artemisinin 10,11 and Bald's Eyesalve 2,12,13 are high-profile examples, as well as the work of Larry Principe in reconstructing alchemical recipes 14,15 and an interdisciplinary team working on the therapeutic potential of recipes in medieval Arabic medical texts 16 ). It is not always easy to clearly communicate that while these parallel aims are interlinked, they are different.…”