Cinchonine (Cinchona Quinoline Alkaloid · Antimalarial · P-gp Inhibitor)

Compound	Cinchonine
Chemical class	Alkaloid — Quinoline (Cinchona bark; desmethoxy analogue of quinine)
CAS	118-10-5
Primary source	Cinchona pubescens, Cinchona officinalis (bark) — minor alkaloid alongside quinine
Key applications	Antimalarial, haemozoin formation inhibitor, antiparasitic, antifungal
Claim strength	Moderate
Typical form	Cinchona bark extract (cinchonine as minor alkaloid); cinchonine isolate
Buy from Herbuno	Request availability and bulk pricing →

Name origin: From Cinchona (the genus, named after Ana de Osorio, Countess of Chinchón, whose 1638 treatment for malaria with Cinchona bark is traditionally cited as introducing it to Europe). Cinchonine is the desmethoxy analogue of quinine — it lacks the 6’-methoxy group on the quinoline ring that quinine has. This structural difference gives cinchonine slightly different antimalarial pharmacokinetics and spectrum but similar overall mechanism. Traditional use: Cinchona bark preparations traditionally contained the full alkaloid complex (quinine, quinidine, cinchonine, cinchonidine) rather than isolated individual alkaloids. Cinchonine’s contribution to the antimalarial activity of traditional Cinchona preparations was not individually characterised until modern phytochemical analysis. Research trajectory: Cinchonine has documented antimalarial activity (haemozoin formation inhibition), antifungal activity (Candida), antiparasitic activity (Leishmania, Trypanosoma), and P-gp inhibitory activity relevant for reversing multidrug resistance in cancer. It lacks quinine’s well-characterised clinical evidence base but has a legitimate research profile distinct from quinine. Commercial source: Not currently in the Herbuno catalogue. Contact Herbuno for Cinchona extract availability with cinchonine quantification.

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Evidence for Cinchonine Applications

Antimalarial — haemozoin inhibition: Cinchonine inhibits β-haematin (haemozoin) formation in Plasmodium falciparum via the same mechanism as quinine, accumulating in the parasite food vacuole. In vitro activity against both chloroquine-sensitive and chloroquine-resistant Plasmodium strains is documented. Cinchonine showed activity against malaria strains resistant to quinine in some studies. Claim strength: Moderate (in vitro and animal; human data from traditional Cinchona bark use only).

P-gp inhibition — multidrug resistance reversal: Cinchonine inhibits P-glycoprotein (P-gp, MDR1) — the efflux pump responsible for multidrug resistance in cancer cells — more potently than verapamil (a classic P-gp inhibitor) in some comparisons. This P-gp inhibitory activity has attracted research interest for reversing chemotherapy resistance in cancer cells. At the same time, the P-gp inhibition could enhance absorption of co-formulated supplements (similar to piperine) but also raises drug interaction concerns for P-gp substrate drugs. Claim strength: Moderate (in vitro; animal; no human MDR-reversal data).

Antifungal and antiprotozoal: Cinchonine demonstrates activity against Candida albicans, Aspergillus, Leishmania donovani, and Trypanosoma cruzi in vitro. The mechanism involves membrane disruption and interference with sterol biosynthesis. Claim strength: Moderate (in vitro).

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Dosage & Formulator Specification

No established human supplement dose for isolated cinchonine. Traditional Cinchona bark preparations used for malaria contained the full alkaloid complex (quinine + quinidine + cinchonine + cinchonidine) at total alkaloid doses of 500–1,500 mg/day. Contact Herbuno for Cinchona extract availability with full alkaloid profile (quinine, quinidine, cinchonine, cinchonidine) by HPLC.

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Frequently Asked Questions — Cinchonine

Is cinchonine as effective as quinine against malaria?
Cinchonine has similar antimalarial mechanism (haemozoin inhibition) to quinine and documented in vitro antimalarial activity, but its clinical evidence base is far smaller. Quinine has centuries of clinical use and multiple controlled trials establishing efficacy and dosing. Cinchonine lacks this clinical dataset. For malaria treatment, quinine or artemisinin-based therapies (with established clinical evidence) are the appropriate choices; cinchonine is a research compound with potential.

How does cinchonine P-gp inhibition compare to piperine?
Both inhibit P-glycoprotein and could theoretically enhance the absorption of co-administered P-gp substrates. Piperine’s P-gp inhibition is better characterised in human pharmacokinetic studies (the curcumin bioavailability study and others). Cinchonine’s P-gp inhibition is better characterised in cancer multidrug resistance research contexts. Both carry drug interaction risks for P-gp substrate pharmaceuticals (digoxin, cyclosporine, many drugs).

Can cinchonine supplements cause cardiac arrhythmia like quinine?
Cinchonine has weaker sodium and potassium channel-blocking activity than quinine at equivalent doses, giving it a lower cardiac arrhythmia risk profile. However, the QT-prolonging potential of Cinchona alkaloids as a class means that high-dose cinchonine preparations should be used with appropriate cardiac advisory language. At sub-therapeutic doses from Cinchona extract, cardiac risk is considered low but not absent in susceptible individuals.

Where is cinchonine found relative to quinine in Cinchona bark?
Cinchona bark contains four primary alkaloids: quinine (dominant, ~40–80% of total alkaloid), quinidine (~5–15%), cinchonidine (~5–10%), and cinchonine (~5–10%). The exact ratios vary by Cinchona species, growing region, bark age, and part of the tree (trunk vs branches). Commercial cinchonine is typically produced by isolation from Cinchona bark extract after the primary quinine has been removed.

Related compounds: Quinine, Quinidine, Camptothecin, Piperine

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Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.

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