Alkaloids are a very mixed group of plant constituents that contain a nitrogen-bearing molecule that makes them particularly pharmacologically active. Despite this chemical similarity, the structures and functions vary so widely it would be very silly to link all “alkaloids” together. And though they may be subdivided into various categories based on their structure there is still large variability even within these groups. The major groups of alkaloids are as follows:
Some are well-known drugs that have a recognized medicinal use. Vincristine for example found in Vinca sp. (Periwinkle) is used to treat some types of cancer. Other alkaloids such as atropine found in Atropa belladonna (deadly nightshade) have a direct effect on the body, reducing spasms, relieving pain, drying up bodily secretions, and dilating the pupils during eye procedures.
Alkaloids are found most commonly in around 20 families of flowering plants. Some of the most important among these are Apocynaceae (the richest family by a large margin), Asteraceae, Berberidaceae, Boraginaceae, Fabaceae, Papaveraceae (a particularly rich source though less than the Apocynaceae), Ranunculaceae, Rubiaceae, Rutaceae and Solanaceae. Alkaloids serve diverse purposes in plants. These include storage and transport of acids, antioxidant protection, and anti-predation effects.
Free alkaloids (bases) are generally soluble in ethanol and other organic solvents, but only slightly soluble in water. In fact, tinctures were largely developed because they are very efficient (using about 45% ethanol) at extracting alkaloids and alkaloid salts from plants.
Alkaloids are readily and irreversibly precipitated by tannins. Therefore alkaloid-containing and significant tannin-containing plants should never be mixed together directly, unless one wishes to counteract the actions of alkaloids. Black tea (Camellia sinensis), cranesbill (Geranium maculatum) or witch hazel (Hamamelis virginiana) are three remedies commonly used for alkaloid poisoning.
Tropane alkaloids are synthesized ultimately from the amino acids ornithine, putrescine (decarboxylated ornithine), or proline. They contain a pyrrolidine and piperidine ring meshed together, and are largely confined to the Solanaceae family, though some are found sprinkled through other families.
|HyoscyamineAtropineScopolamine||Datura stramonium (Jimson weed, thorn apple)Atropa belladonna (deadly nightshade) folia or radixHyoscyamus niger (henbane)||Anti-cholinergicMydriatic (dilates pupils)SpasmolyticAnti-secretory
|cocaine||Erythroxylum coca (Bolivian coca)||First modern local anesthetic, narcotic|
The most well known tropane alkaloids are atropine, hyoscyamine and scopolamine, found exclusively in Solanaceae family plants. These alkaloids are all anticholinergic and are used to decrease smooth muscle spasms and reduce secretions, particularly in the digestive tract. Scopolamine is also used to prevent motion sickness and as presurgical medication because of its unique central nervous system depressing effects, not seen with hyoscyamine. Higher doses of hyoscyamine are hallucinogenic, and these plants have historically been used for ritual purposes. An important bronchodilator drug, ipratropium, is a synthetic derivative of hyoscyamine.
There are several important medicinal isoquinoline alkaloids. These alkaloids are all ultimately synthesized from tyrosine in plants.
|berberine||Hydrastis canadensis (goldenseal) radix–also contains hydrastine and canadineMahonia aquifolium (Oregon grape) radix–also contains berbamine||bitter digestive stimulant, gastrointestinal tonic, antimicrobial, immune stimulant|
|papaverine, morphine, codeine||Papaver somniferum (opium) latex||analgesic, antitussive, sedative narcotic|
|emetine||Cephaelis ipecacuanha (ipecac) radix||emetic (high dose), expectorant (low dose), anthelmintic (medium dose)|
|sanguinarine, etc.||Sanguinaria canadensis (bloodroot) radix||antimicrobial, antineoplastic|
|palmatine, etc.||Jateorhiza palmata (calumba)||bitter digestive stimulant|
Pyridine alkaloids are synthesized ultimately from lysine in plants. Some examples of medicinally relevant pyridine alkaloids are listed below.
|lobeline||Lobelia inflata (lobelia) herba||nicotinic agonist, spasmolytic, expectorant|
|nicotine||Nicotiana tabacum (tobacco) folia||nicotinic agonist, addictive|
|trigonelline||Trigonella foenum-graecum (fenugreek) semen||possibly hypolipidemic|
|piperine||Piper longum (long pepper) fructus||increases gut permeability|
Pyrrole alkaloids are synthesized ultimately from ornithine in plants. No major medicinally important representatives known.
Pyrrolizidine alkaloids (PA) are synthesized ultimately from ornithine in plants. They are medically relevant due to the existence of significant hepatotoxins among the group. The Asteraceae and Boraginaceae families are notable for widespread presence of PAs. Note: Only PAs with unsaturated necine bases are hepatotoxic. Saturated bases (such as found in Echinacea spp and Arnica spp) are non-toxic.
The toxic unsaturated bases only become dangerous after undergoing liver metabolism to alkylating pyrrole esters by the cytochrome P450 enzyme system in the liver. These electrophilic intermediates readily attack DNA. Since they are formed in the liver, they tend to cause their greatest damage to hepatocytes.
Hepatocytes are destroyed and fibrosis tends to replace them. This damage is greatest around the venules in the liver. With sufficient intake of unsaturated PA, fibrosis can obstruct blood flow through the liver sufficient to cause a condition known as hepatic veno-occlusive disease (HVOD). Jaundice and liver failure can ensue, ending ultimately in death in some people who are particularly sensitive or heavily affected unless liver transplantation is available. Activated unsaturated PAs can have toxic effects on other tissues, particularly the kidneys, if they get into circulation. Thus unsaturated PAs should not be seen solely as hepatotoxins.
PAs do not affect everyone equally. This may be a result of differences in cytochrome P450 activity, differences in levels of intake, or other variables. Even moderately large doses of PA tend to have no acute toxicity, only the chronic problem noted above.
Intake of several milligrams a day of PA is sufficient to cause liver damage in susceptible hosts within three months.
It should also be noted that the hepatoprotective saponin glycoside glycyrrhizin found in Glycyrrhiza glabra (licorice) has been shown to protect rats’ livers from the highly toxic pyrrolizidine alkaloid retrorsine
|symphytine, etc.||Symphytum officinale (comfrey) radix||hepatotoxic|
|various||Tussilago farfara (Eastern coltsfoot) radix||hepatotoxic|
|Various||Borago officinalis (borage) herba||hepatotoxic|
Quinoline alkaloids are ultimately synthesized from tryptophan or tryptamine in plants. They are unusual in that they contain two nitrogens, one inside and one outside the main skeleton. One of the first pharmaceutical drugs of global importance, quinine, is a quinoline alkaloid. Crude extracts of Cinchona were used successfully for many years to treat malaria, with isolated quinine eventually replacing them.
|quinine, quinidine||Cinchona spp (Peruvian bark) cortex||anti-malarial, febrifuge, relieve muscle cramps, bitter digestive stimulant|
|cusparine||Galipea officinalis (Angostura) cortex||bitter digestive tonic|
Indole alkaloids are derived synthetically from tryptophan or tryptamine in plants. These compounds also contain two nitrogens. Dimeric forms exist (two indoles hooked together) resulting in four nitrogen compounds. A large number of medicinal alkaloids are found in this group, including some of the most spectacularly active agents such as the potent anticancer drugs vincristine and vinblastine.
|vinblastine, vincristine (note: dimeric)||Catharanthus roseus (Madagascar periwinkle) herba||antineoplastic|
|ergometrine group, ergotamine group, ergotoxine group||Claviceps purpurea (rye ergot) sclerotium||migraine relief, vasoconstriction (anti-hemorrhagic), hallucinogenic|
|reserpine||Rauvolfia serpentina (Indian snakeroot) radix||indirect hypotensive (medium dose), anti-psychotic (high dose)|
|physostigmine||Physostigma venenosum (ordeal bean) semen||miotic (pupil constriction), cholinesterase inhibitor (indirect cholinergic stimulant)|
|yohimbine||Pausinystalia yohimbe cortex||alpha adrenergic antagonist|
|gelsemine||Gelsemium sempervirens (gelsemium) radix||cardiotonic, anti-neuralgic, toxic|
|strychnine||Strychnos nux vomica semen||bitter, toxic|
|beta-carbolines (harmine, harmaline)||Banisteriopsis spp (ayahuasca)||hallucinogenic|
The so-called “methyl xanthines” are synthesized by plants from the purine nucleic acid xanthine with attached methyl groups.
|caffeine||Camellia sinensis (tea) folia, Coffea arabica (coffee) semen, Cola nitida (kola) semen, Paullinia cupana (guaraná) semen, Ilex paraguaensis (maté) folia||CNS stimulant, diuretic (weak), mildly addictive, bitter|
|theobromine||Theobroma cacao (chocolate) semen||similar to caffeine, quite bitter, antioxidant?|
|theophylline||same as caffeine||CNS stimulant, diuretic (strong), antispasmodic|