20 August 2018

Glycyrrhizin – a sweet poison

Glycyrrhizin or glycyrrhic acid is a saponine  found in licorice used as a natural sweetener extracted from Glycyrrhiza glabra. Its name comes from Greek (glykys, sweet, and rhiza, root). The plant is native in many countries of the eastern part of Southern Europe, Middle East and Asia, and it has been introduced in the western part of South Europe and north African countries as well.

Licorice has been extensively used for its pharmaceutical properties in traditional medicine, as an expectorant and to increase blood pressure. It can be found in many soft drinks, food products, snacks and herbal medicines, among others.

Mechanism of action includes inhibition of the enzyme 11-ß-HSD, responsible of cortisol metabolism in the kidney, and stimulation of the mineralocorticoid receptors. This causes cortisol levels to increase and fall of potassium levels, leading to a significant rise in blood pressure, as well as abnormal heart rhythm, edema, lethargy and congestive heart failure.

Doses of 50g of black licorice/day for a period of two weeks can trigger the symptoms described before. In addition, licorice can interact with some medications, such as warfarin, decreasing their effectiveness. The symptoms can disappear rapidly after stopping the consumption of licorice. Recently, consumption on pregnant women has been not recommended.

Canonical SMILES
CC1(C2CCC3(C(C2(CCC1OC4C(C(C(C(O4)C(=O)O)O)O)OC5C(C(C(C(O5)C(=O)O)O)O)O)C)C(=O)C=C6C3(CCC7(C6CC(CC7)(C)C(=O)O)C)C)C)C

References

• Pubchem: https://pubchem.ncbi.nlm.nih.gov/compound/Glycyrrhizic_acid
• Wikipedia: https://en.wikipedia.org/wiki/Glycyrrhizin
• U.S. FDA: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm277152.htm
• Nazari, Somayeh, Maryam Rameshrad, and Hossein Hosseinzadeh. “Toxicological Effects of Glycyrrhiza Glabra (Licorice): A Review.” Phytotherapy Research: PTR 31, no. 11 (November 2017): 1635–50. https://doi.org/10.1002/ptr.5893.
• Sigurjónsdóttir HA, null, L. Franzson, K. Manhem, J. Ragnarsson, G. Sigurdsson, and S. Wallerstedt. “Liquorice-Induced Rise in Blood Pressure: A Linear Dose-Response Relationship.” Journal of Human Hypertension 15, no. 8 (August 2001): 549–52. https://doi.org/10.1038/sj.jhh.1001215.
• Omar, Hesham R., Irina Komarova, Mohamed El-Ghonemi, Ahmed Fathy, Rania Rashad, Hany D. Abdelmalak, Muralidhar Reddy Yerramadha, Yaseen Ali, Engy Helal, and Enrico M. Camporesi. “Licorice Abuse: Time to Send a Warning Message.” Therapeutic Advances in Endocrinology and Metabolism 3, no. 4 (August 2012): 125–38. https://doi.org/10.1177/2042018812454322.

Pictures

1. Structure of Glycyrrhizin. By Yikrazuul [Public domain], from Wikimedia Commons: https://upload.wikimedia.org/wikipedia/commons/0/02/Glycyrrhizic_Acid.svg 
2. Glycyrrhiza gabra. http://commons.wikimedia.org/wiki/File:Koeh-207.jpg 
3. Palodul. https://www.badaccu.com/semillaygrano/50-g-regaliz-palo-palodul-palulu-palocaz%C3%BA-19785 
4. Pastillas Juanola. https://cincodias.elpais.com/cincodias/2015/01/30/sentidos/1422638196_468069.html  
5. Swedish lakrits. https://www.allas.se/fordelar-med-lakrits/