Cinchona

Importance, Distribution and Botanical Features

The commercial value of Cinchona comes almost entirely from the alkaloids, quinine and quinidine, extracted from the bark: a subsidiary use for the remainder of the tree is as a fuel wood for fires.

Quinine has been used for centuries for the suppression and treatment of malaria, being administered as the sulphate, bisulphate, hydrochloride and dihydrochloride (British Pharmacopaeia 1973). The use of quinine for these purposes has decreased with the development since the 1940’s of synthetic anti-malarial drugs (e.g. Chloroquine, Proguanil). Resistance of the malarial parasite to the synthetic antimalarials is widely recorded but much less so to quinine, thus quinine can often still be used either alone or in mixture, in areas where the “synthetics” are ineffective. Further factors in favour of using quinine are its relatively low price (£ 40 per kg in 1985) and wide availability. Additional important uses for quinine are as a treatment for “night cramps”, as a bittering and brightening agent in the soft drinks and food industry and as the starting material for the industrial production of quinidine.

Quinidine can also be used to treat malaria, but its main and increasing use is in the prophylaxis of cardiac arrhythmias and in the treatment of atrial fibrillation.

The genus Cinchona L. belongs to the family Rubiaceae and encompasses some 15 to 40 species indigenous to a relatively small tropical rainforest area of the Andean mountain slopes of South America, but now widely planted in humid regions of South and Central America, Africa, India, Indonesia, Hawaii and Australia where soil pH is in the range 4.6 to 6.5 and where temperature is within 7° to 26 °C. All the species of Cinchona are either small trees or shrubs.

The taxonomy of the genus is confused, in spite of a number of attempts to classify the wide range of phenotypes found in plantations and in natural stands. All species so far examined show a diploid chromosome complement of 2n = 34. The flowers exhibit heterostylism, substantial self-incompatibility and protandry and the ready hybridisation of these outbreeding species has resulted in considerable difficulty in the allocation of phenotypes to species. Within the genus only six species are considered to be of current economic interest: C. calisaya, C hybrida, C. offtcinalis, C. robusta, C. ledgeriana (considered to be a variety of C calisaya or a hybrid) and C succirubra (syn. C pubescens). C. ledgeriana and C. succirubra dominate commercial plantings.

Traditional Cropping

Agriculture

Plantations can be established using trees raised from seed or by layering, grafting or budding onto similar or different Cinchona species rootstocks. Where seeds are used, they have to be sown in shaded beds, transplanted after 4-5 months and grown on until they are 2-3 years old. From plantation to plantation there is much variation in management, but typically transplants are established at ca. 8000 ha-1 (1.2 m between plants on a triangular plant). Weed control is by herbicides for about 5 years: NPK fertilizers are applied from year 2 onwards. Pest control is ad hoc. During the early stages of crop growth multiple crowns may develop: these are removed together with the lower branches, and the bark from such thinnings is removed and sold. Phytophthora cinnamomi (Stripe canker) is an increasingly important pathogen resulting in the death of considerable numbers of trees and the abandonment of some plantations. Resistance factors are unknown, but the disease or its spread may be associated with impaired soil drainage. Other important pathogens include P. palmivora, Pythium vexans and Pellicularia salmonicolor ().

The mature plantations, with trees typically 8-16 m tall are clear felled at 7-16 years after planting. The bark of all but the thinnest branches is beaten by hand, to allow the bark to be peeled prior to its sun drying, pulverisation, bagging and shipping. In the field, 70% of the cut stumps will regrow for a further 7-16-year cropping cycle, but only about 45% will survive for the third cycle. These coppiced stumps can be grafted with “superior” scions for each cropping cycle.

Crop Processing and Yields

Alkaloids in the bark are present as salts of various organic acids, but are extracted as the free alkaloids. Typically, the pulverised bark is finely ground, basified with lime and soxhlet extracted in hot toluene. Dilute H2S04 is reacted with the organic extract and the aqueous phase concentrated, at which point the quinine sulphate crystallises out of solution. The other alkaloids are precipitated from the aqueous phase by alkali treatment and further purified. The toluene is recovered for re-use and the extracted bark is discarded.

There is much variation in the parameters contributing to crop yield, e.g. growth rate, disease resistance, alkaloid synthesis rate, bark to trunk thickness ratio that results from the heterozygous genetic base (): this is reflected by the spread of average yields. Although the “average” bark contains 7% – 12% total alkaloids, this is a mixture of more than 30 compounds. Of these alkaloids, quinine accounts for 70%-90%, cinchonidine for l%-3% and quinidine for up to 1% of the mixture. Quinine in bark samples from different sources averages from 3%-7%, with certain countries (e.g. Kenya) producing much higher grade bark (up to 10%). Analysis of individual trees shows that specimens can readily be found with 14% quinine in the bark and occasionally with up to 25%. Attempts to improve the alkaloid yield of seedling-derived trees by breeding from “superior” parents has had considerable success but crops are still heterogenous. Clonal propagation by conventional techniques (e.g., layering or grafting) is expensive, while the rooting of cuttings taken from the highest yielding trees has proved particularly difficult.

The world market for quinine is approximately 4001 (about 1001 in Europe, 2001 in the U.S.A.). Approximately 50% of all quinine is used for the synthesis of quinidine.