The Fever Tree: from Malaria to Neurological Diseases

Abstract

This article describes the discovery and use of the South American cinchona bark and its main therapeutic (and toxic) alkaloids, quinine and quinidine. Since the introduction of cinchona to Europe in the 17th century, it played a role in treating emperors and peasants and was central to colonialism and wars. Over those 400 years, the medical use of cinchona alkaloids has evolved from bark extracts to chemical synthesis and controlled clinical trials. At the present time, the use of quinine and quinidine has declined, to a large extent due to their toxicity. However, quinine is still being prescribed in resource-limited settings, in severe malaria, and in pregnant women, and quinidine made a limited comeback in the treatment of several cardiac and neurological syndromes. In addition, the article presents more recent studies which improved our understanding of cinchona alkaloids’ pharmacology. The knowledge gained through these studies will hopefully lead to a wider use of these drugs in precision medicine and to design of new generation, safer quinine and quinidine derivatives.

Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2

“…Quinine and quinidine, both content of the Chinchona bark, are alkaloids and stereoisomers of each other [ 43 ]. The first records for medical use of quinine date back to 1630, where in Peru, the countess of Chinchon developed malaria and was successfully treated with an extract of the bark of the fever tree, which was later termed Chinchona bark [ 49 ]. First isolated in 1820 and chemically synthesized in 1944, it was the only antimalarial drug available [ 49 ].…”

“…The first records for medical use of quinine date back to 1630, where in Peru, the countess of Chinchon developed malaria and was successfully treated with an extract of the bark of the fever tree, which was later termed Chinchona bark [ 49 ]. First isolated in 1820 and chemically synthesized in 1944, it was the only antimalarial drug available [ 49 ]. In the 19th century, British citizens and soldiers used tons of the Chinchona bark to protect themselves from malaria and thus permitted a stable British population in tropical colonies.…”

Estimation Of The Preliminary Screening Of Phytochemicals, Total Phenolic Content, Total Flavonoid Content, Antioxidant And Alpha-Amylase Inhibitory Activities Of The Selected South African Plant Extracts For Medicinal Purposes

“…They provide protective effects on plants against predators such as insects (War et al, 2012, Furstenberg-Hagg et al, 2013. Furthermore, alkaloids have diverse medicinal properties such as relief of pain (morphine) (Shoaib et al, 2016, Hussain et al, 2018, treat analgesic (codeine) (Bhandari et al, 2011), treatment of arrhythmias (quinidine) (Eyal, 2018), and useful for blood-vessel constrictors (ergonovine and ephedrine) (Hartmann, 2004). In addition to this, ergonovine is used to reduce uterine haemorrhage after birth (Weeks, 2015, Chelmow, 2008, and finally, ephedrine has been used often for the relief of discomfort associated with common colds, sinusitis, hay fever, and bronchial asthma (Thacher, 1946).…”

Pharmacological Advances of Chloroquine and Hydroxychloroquine: From Antimalarials to Investigative Therapies in COVID-19

“…Quinidine, for instance, has shown therapeutic effects for arrhythmia and Alzheimer's disease. 5 CQ and HCQ, 2 of the most commonly used quinine derivatives, have been constantly studied and utilized for more disease states beyond malaria. 1).…”