Cinchona Bark Extract
Also known as: Cinchona officinalis, C. ledgeriana, C. succirubra, Cinchona Bark Extract
Overview
Cinchona bark extract is derived from the dried bark of *Cinchona* species, primarily *Cinchona officinalis*, *C. ledgeriana*, and *C. succirubra*. It is characterized by its quinoline alkaloid content, including quinine, cinchonine, cinchonidine, and quinidine, with total alkaloid content standardized to ≥4.75%. Historically, it has been used to treat malaria and cardiac arrhythmias. Quinine, the most abundant alkaloid, inhibits heme polymerization in the malarial parasite. Quinidine exhibits antiarrhythmic properties by blocking sodium and potassium channels in the heart. While its anti-malarial use has diminished due to artemisinin-based therapies, it remains relevant in artemisinin-resistant cases. Emerging research explores its potential cytotoxic and antimicrobial activities.
Benefits
Cinchona bark extract's primary benefit lies in its historical use for malaria treatment, particularly in cases resistant to artemisinin-based therapies. This is supported by Cochrane reviews and historical data. The quinidine content contributes to antiarrhythmic effects by blocking sodium and potassium channels. Secondary benefits, primarily observed in vitro, include cytotoxic activity against cancer cells, with *C. officinalis*-loaded nanoparticles showing an IC50 of 62.5 μg/mL against MCF-7 breast cancer cells. Additionally, the alkaloids demonstrate antimicrobial activity against *Plasmodium* species at concentrations ≥2.5 μg/mL. However, clinical evidence for these secondary benefits is limited.
How it works
The mechanism of action for Cinchona bark extract varies depending on the application. In malaria treatment, quinine inhibits heme polymerization within the digestive vacuoles of the *Plasmodium* parasite, disrupting its life cycle. For cardiac applications, quinidine blocks voltage-gated sodium and potassium channels in heart cells, prolonging the action potential and exerting antiarrhythmic effects. Quinine exhibits good oral bioavailability, with 76-88% absorption and a Tmax of 3-5 hours. The cytotoxic effects observed in vitro are linked to caspase-3 activation, leading to apoptosis in cancer cells.
Side effects
Common side effects of Cinchona bark extract include cinchonism, characterized by tinnitus, headache, and nausea, occurring in more than 5% of users. Uncommon side effects (1-5%) include hypoglycemia and QT prolongation. Rare but serious side effects (<1%) include thrombocytopenia and hemolytic anemia. Drug interactions include increased toxicity risk with CYP3A4 substrates, elevated digoxin serum levels, and increased bleeding risk with warfarin. Cinchona bark extract is contraindicated in individuals with G6PD deficiency and cardiac conduction disorders. Due to the risk of cumulative toxicity, long-term use beyond 7-10 days is not recommended.
Dosage
For malaria treatment, the recommended dosage is 8-12 mg/kg of quinine equivalent every 8 hours for 10-14 days. However, the use of Cinchona bark extract as a general supplement is not well-established, and caution is advised due to the risk of alkaloid toxicity at doses exceeding 1g/day. Standardized extracts typically contain 5-7% total alkaloids. Nanoparticle formulations are being explored to enhance delivery, but these are currently in preclinical stages. Due to the potential for significant side effects, it is crucial to consult with a healthcare professional before using Cinchona bark extract.
FAQs
Can it replace prescription antimalarials?
No, artemisinin derivatives are the first-line treatment for malaria. Cinchona bark extract should only be used under medical supervision, particularly in cases of artemisinin resistance.
Typical onset of effects?
Antipyretic effects in malaria typically occur within 24-48 hours. Cardiac effects from quinidine can be observed within 1-2 hours after administration.
Safe for long-term use?
No, long-term use is not recommended due to the risk of cumulative toxicity beyond 7-10 days. Consult with a healthcare professional for appropriate duration and monitoring.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6193530/ – This analytical validation study focused on quantifying the alkaloid content in Cinchona bark extract using a Supercritical Fluid Chromatography (SFC) method. The study found that the extract contained between 4.75-5.20% total alkaloids, highlighting the importance of standardized extraction methods. However, the study did not measure any clinical outcomes related to the extract's use.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9565860/ – This preclinical in vitro study investigated the cytotoxic effects of Cinchona officinalis extract on MCF-7 breast cancer cells. The study found that the extract induced dose-dependent apoptosis through caspase-3 activation, suggesting a potential anti-cancer mechanism. However, the findings are limited to in vitro observations and require further validation in human studies.
- https://www.jameslindlibrary.org/articles/evaluating-cinchona-bark-and-quinine-for-treating-and-preventing-malaria/ – This resource from the James Lind Library evaluates the historical use of Cinchona bark and quinine for treating and preventing malaria. It supports the role of quinine in treating resistant cases of malaria, particularly in the pre-artemisinin era. The analysis emphasizes the importance of optimizing quinine treatment strategies based on historical evidence and systematic review methodology.
- https://biointerfaceresearch.com/wp-content/uploads/2022/09/BRIAC134.319.pdf – This research article likely details specific findings related to Cinchona bark extract, potentially focusing on its bioactive compounds or applications. A more detailed summary would require access to the full text of the article to understand its methodology and key insights. The article could provide valuable information on the extract's properties and potential uses.
