From 1349 onwards, there were regular outbreaks of the plague in the Low Countries and the last outbreak in the Northern Netherlands was in 1636. After that, there were several smaller outbreaks. At that time, it was not clear what caused the disease, at least not according to our modern concepts. Nevertheless, various plants with a potential antibacterial effect were used at the time in an attempt to combat the plague. An old recipe shows which plants were used for this purpose, among others.
Nettie Stoppelenburg en Maaike van Kregten. Tijdschrift voor Fytotherapie 2022 nr 1.
Translations are by me: corrections are welcome!
The plague is caused by the bacterium Yersinia pestis. At the time, people already had an idea of contagiousness, partly because the spread of the disease was limited by isolating the sick and nursing them separately. In many cities, therefore, special hospitals for the treatment of the plague were set up. Miasmas or ‘bad airs’, which were believed to bring the disease, were kept at bay by burning aromatic plants, for example. Plague doctors also burned these herbs in the characteristic beak mask that was part of their protective clothing .
The recipe for ‘Plague water’, from the archive of House Amerongen , probably dates from around 1720. In November of that year, the city council of Utrecht was startled by reports of an outbreak of the plague in France. Although it was feared that the disease would be transmitted by travellers, no immediate action was taken. It was not until October 1721 that the decision was made to set up a plague hospital. A plague master was also appointed, and pharmacists were required to stock certain herbs . On 22 November 1721, a ‘List of simple and composed medicines against the plague, which are necessarily required in the pharmacies, prepared at the request of the honourable Lords of the City of Utrecht by its ordinaries’, was published. This list includes twelve of the fourteen plants in the recipe discussed here, namely: angelica, gentian root, zedoary root, blessed thistle (above ground parts and seed), common centaury, lemon balm, rue, mint, rosemary, water germander, sage and marigold .
The recipe was found on a single leaf, it is not part of a book. It was probably copied; recipes were often copied and exchanged. The R/ of recipe (one takes), suggests that the recipe came from a doctor, although in those days it was not unusual for pharmacists to write prescriptions as well. Since the plants used were also the official medication used against the plague at the time, the suspicion that the original recipe may have come from someone with medical training seems confirmed.
Of the fourteen herbs mentioned here, thirteen have been identified from Dodonaeus’ Cruydt-boeck (see Table 1) . Snake root could possibly be Calla palustris, but according to Dodonaeus it was called ‘snakeweed’. It may also be the root of snakeweed. Because this is too uncertain, and because no relevant research results can be found, this plant has been left out of consideration. Of Teucrium scordium L. only studies with other species of Teucrium have been found; therefore this plant has also been left out of consideration.
|Name (Dutch/English)||Botanical name||Showed effect against:|
|Goudsbloem / Marigold||Calendula officinalis||Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae |
|Rozemarijn / Rosemary||Salvia rosmarinus (syn: Rosmarinus officinalis)||E. coli [2,3,7,10], K. pneumoniae , Salmonella typhimurium [3,8,10] Salmonella enteriditis , Yersinia enterocolitica [7,8,10] Shigella flexneri |
|Wijnruit/Rue||Ruta graveolens||E. coli, K. pneumoniae, S. typhimurium [3,4]|
Enterobacter cloacea, Citrobacter freundii 
|Salie/Sage||Salvia officinalis||E. coli [2,5], S. typhimurium |
|Melisse/Lemon balm||Melissa officinalis||E. coli, S. typhimurium |
|Kruizemunt/Spearmint||Mentha spicata||Y. enterocolitica |
|Sc(h)ordium /water germander||Teucrium scordium||Nothing found|
|Centaur[ium] minor / common centaury||Centaurium erythraea||E. coli, E. cloacae, S. typhimurium |
|Card. benedictus, gezegende distel / blessed thistle||Centaurea benedicta||Cnicine: E. coli [12,13], Proteus mirabilis, S. typhimurium ,|
K. pneumoniae 
|Betonie / betony||Betonica officinalis (syn. Stachys officinalis)||E. coli, S. typhimurium |
|Engelwortel / Angelica||Angelica spp.||Y. enterocolitica, E. coli, S. typhimurium |
|Zedoariawortel / zedoary root||Curcuma zedoaria||P. mirabilis, K. pneumoniae  E. coli, Proteus vulgaris,|
Salmonella typhimurium 
|Gentianawortel / gentian root||Gentiana spp.||G. lutea,leaf and flower: E. coli, S. typhimurium, S. enteritidis, E. cloacae |
|Slangewortel / snake root||Calla palustris?||Not identified/ nothing found|
For references of the table please send an e-mail to firstname.lastname@example.org
Antibiotics ultimately helped greatly in fighting the plague, but the disease still exists today. In order to find out whether the plants in this recipe might have an antibacterial effect, PubMed was first searched for the plague bacterium Yersinia pestis in combination with the plant name. As expected, no results were found. Then pestis was omitted, based on the idea that other Yersinia species are probably quite similar to Y. pestis. Plants that have an antibacterial effect on them might then -in theory- also show activity against Y. pestis.
A broader search was then carried out for the antibiotic activity of the plants concerned. The results were filtered according to the Enterobacteriaceae family of gram-negative bacteria, such as Escherichia coli and Klebsiella, and which also includes Yersinia spp. This, again, with the idea that bacteria from the same group might also react in somewhat similar ways to these plants. Finally, as a check, we looked for similarities in efficacy with antibiotics currently used against plague, such as tetracyclines (doxycycline), aminoglycosides (streptomycin, gentamicin), fluoroquinolones (ciprofloxacin) and chloramphenicol .
All twelve remaining plants showed antibacterial activity in vitro against gram-negative bacteria, three of which were also against Yersinia enterocolitica, namely rosemary, spearmint and angelica [6,7,10]. In a sensitivity study on Y. enterocolitica, the essential oil (EO) of rosemary in that test design showed a greater zone of inhibition than the antibiotics tetracycline and chloramphenicol. In addition, it had an effect equal to that of nalidixic acid (fluoroquinolone). In this study, the zone of inhibition of Angelica-EO on this bacterium was as large as that of tetracycline . In another study, rosemary was found to have a bactericidal effect on Y. enterocolitica . The first study also shows that the three antibiotics tested that are effective against Y. enterocolitica, namely tetracycline, chloramphenicol and nalidixic acid, are precisely the antibiotics – or their derivatives – that are still used today against Y. pestis .
The table does not specify the parts of the plant used or the extraction methods. The studies were all in vitro experiments, such as agar diffusion tests and minimal inhibition concentration tests. Thus, nothing can be said about a effective, safe dosage, or about the in vivo effect of the herbal preparations after ingestion. Thus, only indirect indications have been observed here. Therefore, no firm conclusions can be drawn about the efficacy of these plants on the plague bacteria; these are possibilities that could be further explored.
Nevertheless, it is interesting that, at a time when people had no idea of the existence of bacteria, they used herbs that later proved to have an antibacterial effect and, moreover, against a close relative of the plague bacterium. It might be worthwhile to re-evaluate the similar recipe discussed here for antimicrobial applications in the present day with current techniques and knowledge.
Many thanks to Dr. E. (Eric) van Kregten, physician-microbiologist (retired) for advice on the microbiological part of the text.
 Algera M. Mens en medicijn. Geschiedenis van het geneesmiddel. Meulenhoff Amsterdam 2000: 190-1.
 Archief van het huis Amerongen. Utrechts Archief toegang 1001, inventarisnummer 5152.
 Stadsbestuur van Utrecht 1577-1795. Utrechts Archief toegang 702, inventarisnummer 451.
 Dodonaeus R. Cruydt-boeck. Antwerpen: Balthasar Moretus: 1644. leesmaar.nl/cruydtboeck/alfabetisch/herkend_c.htm; geraadpleegd: 23-11-2021.
 RIVM. Richtlijnen en draaiboeken: pest. lci.rivm.nl/richtlijnen/pest; geraadpleegd: 27-11-2021.
 Rota C. et al. In vitro antimicrobial activity of essential oils from aromatic plants against selected foodborne pathogens. J Food Prot. 2004;67(6):1252-1256.
 Ekhtelat M. et al. Chemical composition and antibacterial effects of some essential oils individually and in combination with sodium benzoate against methicillin-resistant Staphylococcus aureus and Yersinia enterocolitica. Vet Res Forum. 2020;11(4):333-338.
 Elgayyar M. et al. Antimicrobial activity of essential oils from plants against selected pathogenic and saprophytic microorganisms. J Food Prot. 2001;64(7):1019-1024.