PT - JOURNAL ARTICLE AU - Blessing O Anonye AU - Valentine Nweke AU - Jessica Furner-Pardoe AU - Rebecca Gabrilska AU - Afshan Rafiq AU - Faith Ukachukwu AU - Julie Bruce AU - Christina Lee AU - Meera Unnikrishnan AU - Kendra P. Rumbaugh AU - Lori AS Snyder AU - Freya Harrison TI - The safety profile of Bald’s eyesalve for the treatment of bacterial infections AID - 10.1101/2020.04.23.041749 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.04.23.041749 4099 - http://biorxiv.org/content/early/2020/04/24/2020.04.23.041749.short 4100 - http://biorxiv.org/content/early/2020/04/24/2020.04.23.041749.full AB - The rise in antimicrobial resistance has prompted the development of alternatives, such as plant-derived compounds, 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 grown in an in vitro model of soft tissue infection. This remedy also had bactericidal activity against methicillin-resistant S. aureus (MRSA) in a chronic mouse wound. 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 minutes. The slug mucosal irritation assay revealed that a low level of mucus was secreted by slugs exposed to eyesalve, indicating mild 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.Importance Alternative treatment for bacterial infections are needed to combat the ever increasing repertoire of bacteria resistant to antibiotics. A medieval plant-based remedy, Bald’s eyesalve, shows promise as a substitute for the treatment of these infections. For any substance to be effective in the treatment of bacterial infections in humans, it is important to consider the safety profile. This is a key consideration in order to have the necessary regulatory approval. We demonstrate the safety profile of Bald’s eyesalve using a variety of models, including whole-organ and whole-animal models. Our results show that Bald’s eyesalve is mildly toxic to cultured human cells, but potentially suitable for patch tests on healthy human volunteers to assess safety for later clinical trials. Our work has the potential to transform the management of diseases caused by bacterial infections, such as diabetic foot ulcers, through topical application of a natural product cocktail based on Bald’s eyesalve.Competing Interest StatementThe authors have declared no competing interest.