Beez Neez now Chy Whella

Cinchona Tree

Big Bear and Pepe Millard

Tue 24 Feb 2009 23:06

Cinchona or Quinine Tree

Cinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cms long. The flowers are white, pink or red, produced in terminal panicles. The fruit is a small capsule containing numerous seeds. South American Indians have been using cinchona bark to treat fevers for many centuries. Spanish conquerors learned of quinine's medicinal uses in Peru, at the beginning of the 17th Century. Use of the powdered " Peruvian bark" was first recorded in religious writings by the Jesuits in 1633. The Jesuit fathers were the primary exporters and importers of quinine during this time and the bark became known as " Jesuit bark.". The use of quinine for fevers was included in medical literature in 1643. Stories of the medicinal properties of this bark, however, are perhaps noted in journals as far back as the 1560’s-1570’s. We saw many of these trees on our 'pram' ride through the rain forest.

Cinchona species are used as food plants by the larvae of some Lepidoptera species including The Engrailed, The Commander, and members of the genus Endoclita including E. Damor, E. Purpurescens and E. Sericeus.

Cinchona alkaloids

The bark of trees in this genus is the source of a variety of 20 alkaloids, the most familiar of which is quinine, an anti-fever agent especially useful in treating malaria. Cinchona alkaloids include: cinchonine and cinchonidine (stereoisomers with R = vinyl, R' = hydrogen), quinine and quinidine (stereoisomers with R = vinyl, R' = methoxy), dihydroquinidine & dihydroquinine (stereoisomers with R = ethyl, R' = methoxy). They find use in organic chemistry as organocatalysts in asymmetric synthesis.

History

The Italian botanist Pietro Castelli wrote a pamphlet noteworthy as being the first Italian publication that mentions the cinchona. By the 1630's (or 1640's, depending on the reference), the bark was being exported to Europe. In the late 1640's, the method of use of the bark was noted in the Schedula Romana, and in 1677 the use of the bark was noted in the London Pharmacopoeia. According to legend, the first European ever to be cured from malaria fever was the wife of the Spanish Viceroy, the countess of Chinchon. The court physician was summoned and urged to save the countess from the waves of fever and chill that were threatening her life, but every effort failed to relieve her. At last the physician administered some medicine which he had obtained from the local Indians, who had been using it for similar syndromes. The countess survived the malarial attack and reportedly brought the cinchona bark back with her when she returned to Europe in the 1640s. The story of her cure is doubtful. Charles II called upon Mr Robert Talbor, who had become famous for his miraculous malaria cure. Because at that time the bark was in religious controversy, Talbor gave the king the bitter bark decoction in great secrecy. The treatment gave the king complete relief from the malaria fever. In return, he was offered membership of the prestigious Royal College of Physicians. In 1679 Talbor was called by the King of France, Louis XIV, whose son was suffering from malaria fever. After a successful treatment, Talbor was rewarded by the king with 3,000 gold crowns. At the same time he was given a lifetime pension for this prescription. Talbor, however, was asked to keep the entire episode secret. After the death of Talbor, the French king found this formula: six drams of rose leaves, two ounces of lemon juice and a strong decoction of the chinchona bark served with wine. Wine was used because some alkaloids of the cinchona bark are not soluble in water, but are soluble in wine.

The birth of homeopathy was based on quinine testing. The founder of homeopathy, Dr. Samuel Hahnemann, when translating the Cullen's Materia Medica, noticed that Dr Cullen wrote that quinine cures malaria and can also produce malaria. Dr. Hahnemann took daily a large non-homeopathic dose of quinine bark. After two weeks, he said he felt malaria-like symptoms. This idea of "like cures like" was the starting point of his writings on "Homeopathy". In 1738, Sur l'arbre du quinquina, a paper written by Charles Marie de La Condamine, a member of the expedition that was sent to Peru to determine the length of a degree of the meridian in the neighbourhood of the equator, was published by the French Academy of Sciencies. In it he identified three separate species. In 1742, on the basis of a specimen received from La Condamine, Linnaeus named the tree Quinquina condaminiae and established a new genus, which he termed Cinchona quinquina condaminiae. In 1753 he described Cinchona officinalis as a separate species.

History of cultivation

The bark was very valuable to Europeans in expanding their access to and exploitation of resources in far off colonies, and at home. Bark gathering was often environmentally destructive, destroying huge expanses of trees for their bark, with difficult conditions for low wages that did not allow the indigenous bark gatherers to settle debts even upon death. In 1860, a British expedition to South America led by Clements Markham brought back Cinchona seeds and plants, which were planted in the Hakgala Botanical Garden in Sri Lanka in January 1861. James Taylor, the pioneer of tea planting in Sri Lanka, was one of the pioneers of Cinchona cultivation. By 1883 about 64,000 acres (260 km²) were in cultivation in Sri Lanka, with exports reaching a peak of 15 million pounds in 1886. In 1865, the "Carlota Colony" was founded in Mexico. Wealthy American post-war confederate leaders were enticed there by the Emporer Maximillian, Archduke of Habsburg. The colony was situated on the direct Mexico-Vera Cruz Highway, and within 50 km. of the railway, which was due to arrive in Cordoba at the end of that year. ... "All that survives today of the ill-fated Carlota Colony are the flourishing groves of cinchonas, the quinine-producing tree which ... at Empress Charlotte's instigation, were first introduced into the country."

Treatments

Cinchona has been used for a number of medical reasons such as: Treats malaria (until the development of synthetic drugs, quinine was used as the primary treatment of malaria, a disease that kills over 100 million people a year). Kills parasites. Reduces fever. Regulates heartbeat. Calms nerves. Stimulates digestion. Kills germs. Reduces spasms. Kills insects. Relieves pain. Kills bacteria and fungi. Dries secretions. Natures own Viagra. The main reason for its use is to treat malaria, but it is rarely used today as many people think it is dangerous, as it can kill if taken in large amounts. Quinidine is used to treat cardiac arrhythmias.

Quinine

Quinine did not gain wide acceptance in the medical community until Charles II was cured of the ague by a London apothecary at the end of the 17th century. Quinine was officially recognized in an edition of the London Pharmacopoeia as "Cortex Peruanus" in 1677. Thus began the quest for quinine. In 1735, Joseph de Jussieu, a French botanist, accompanied the first non-Spanish expedition to South America and collected detailed information about the cinchona trees. Unfortunately, as Jussieu was preparing to return to France, after 30 years of research, someone stole all his work. Charles Marie de la Condamine, leader of Jussieu's expedition, tried unsuccessfully to transfer seedlings to Europe. Information about the cinchona tree and its medicinal bark was slow to reach Europe. Scientific studies about quinine were first published by Alexander von Humboldt and Aimé Bonpland in the first part of the 18th century. The quinine alkaloid was separated from the powdered bark and named "quinine" in 1820 by two French doctors. The name quinine comes from the Amerindian word for the cinchona tree, quinaquina, which means "bark of barks." As European countries continued extensive colonization in Africa, India and South America, the need for quinine was great, because of malaria. The Dutch and British cultivated cinchona trees in their East Indian colonies but the quinine content was very low in those species. A British collector, Charles Ledger, obtained some seeds of a relatively potent Bolivian species, Cinchona ledgeriana. England, reluctant to purchase more trees that were possibly low in quinine content, refused to buy the seeds. The Dutch bought the seeds from Ledger, planted them in Java, and came to monopolize the world's supply of quinine for close to 100 years. During World War II, the Japanese took control of Java. The Dutch took seeds out of Java but had no time to grow new trees to supply troops stationed in the tropics with quinine. The United States sent a group of botanists to Columbia to obtain enough quinine to use throughout the war. In 1944, synthetic quinine was developed by American scientists. Synthetic quinine proved to be very effective against malaria and had fewer side effects, and the need for natural quinine subsided. Over the years, the causative malarial parasite became resistant to synthetic quinine preparations. Interestingly, the parasites have not developed a full resistance to natural quinine.

The chemical composition of quinine is C₂0H₂4N₂O₂^.H₂O. Quinine is derived from cinchona bark, and mixed with lime. The bark and lime mixture is extracted with hot paraffin oil, filtered, and shaken with sulphuric acid. This solution is neutralized with sodium carbonate. As the solution cools, quinine sulphate crystallizes out. To obtain pure quinine, the quinine sulphate is treated with ammonia. Crystalline quinine is a white, extremely bitter powder. The powdered bark can also be treated with solvents, such as toluene, or amyl alcohol to extract the quinine. Current biotechnology has developed a method to produce quinine by culturing plant cells. Grown in test tubes that contain a special medium that contains absorbent resins, the cells can be manipulated to release quinine, which is absorbed by the resin and then extracted. This method has high yields but is extremely expensive and fragile.

Medicinally, quinine is best known for its treatment of malaria. Quinine does not cure the disease, but treats the fever and other related symptoms. Pharmacologically, quinine is toxic to many bacteria and one-celled organisms, such as yeast and plasmodia. It also has antipyretic (fever-reducing), analgesic (pain-relieving), and local anaesthetic properties. Quinine concentrates in the red blood cells and is thought to interfere with the protein and glucose synthesis of the malaria parasite. With treatment, the parasites disappear from the blood stream. Many malarial victims have a recurrence of the disease because quinine does not kill the parasites living outside the red blood cells. Eventually, the parasites make their way into the blood stream, and the victim has a relapse. Quinine is also used to treat myotonic dystrophy (muscle weakness, usually facial) and muscle cramps associated with early kidney failure. The toxic side effects of quinine, called Cinchonism, include dizziness, tinnitus (ringing in ears), vision disturbances, nausea, and vomiting. Extreme effects of excessive quinine use include blindness and deafness.

Quinine also has non-medicinal uses, such as in preparations for the treatment of sunburn. It is also used in liqueurs, bitters, and condiments. The best known non-medicinal use is its addition to tonic water and soft drinks. The addition of quinine to water dates from the days of British rule in India-quinine was added to water as a prevention against malaria. About 40% of the quinine produced is used by the food and drug industry, the rest is used medicinally. In the United States, beverages made with quinine may contain not more than 83 parts per million cinchona alkaloids.