Medical Alkaloid Photos

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Economic Plant Photographs #23

   Medical Glycosides, Terpenes & Alkaloids
    Chemistry Part I       Chemistry Part 2  

Digitalis, Strophanthus, Periwinkle, Rauvolfia, Oleander,
Cerbera, Colchicum, Curare, Absinthe, Brunfelsia & Khat.

Snapdragon Family (Scrophulariaceae)

Foxglove or digitalis (Digitalis purpurea) in full bloom at the Wayne's Word garden. Foxglove is the source of two potent glycosides used as a heart stimulant, digoxin and digitoxin. They are administered for congestive heart failure, weakened heart and irregular heart beat (arrhythmia). These glycosides prolong the relaxation phase of the heart (ventricular diastole), thus allowing the left ventricle to fill with more blood. In accordance with Starling's Law of Contraction, the increased blood volume in the left ventricle results in a more forceful contraction (ventricular systole), thereby pumping more blood out into the aorta artery. After the contraction, as backflow pushes against the aorta semilunar valve, coronary arteries that feed the heart muscle fill with blood. They are able to fill with blood during diastole because the heart relaxes and the coronary vessels are not constricted.

Sunflower Family (Asteraceae)

Vincent van Gogh & The Absinthe Connection

Absinthe, a distilled, highly alcoholic beverage derived from the flowers and leaves of Artemisia absinthium. Depending on the recipe it may contain several additional herbs, including green anise (Pimpinella anisum), sweet fennel (Foeciculum vulgare), melissa (Melissa officinalis) and hyssop (Hyssop officinalis). The natural green color of absinthe comes from dissolved chlorophylls in the herbs. The small flowers in the above image resemble those of North American sagebrush species in the same genus Artemisia. Although it is sometimes referred to as a liqueur, absinthe is not traditionally bottled with added sugar. It is therefore classified as a spirit.

There are several informative on-line references about absinthe, including Wikipedia. Absinthe spoons (left) are designed to hold a sugar cube atop the glass containing absinthe, over which ice-cold water is dripped to dilute the absinthe. The lip near the center of the handle allows the spoon to rest securely on the rim of the glass. Spoon image courtesy of Wikimdia Commons (2012).

Absinthe was among the most popular drinks near the end of the nineteenth century in France—not only in France but across Europe and even in the United States. The following is from Absinthe: The Tale of the Green Fairy by Joe Kissell:

    "But it is more than just a tasty alcoholic beverage: it’s a ritual. To prepare your absinthe in the traditional way, you begin by pouring about an ounce of the greenish liquid into a glass. On top of the glass you place a flat, slotted spoon on which a single sugar cube rests. You pour cold water over the sugar cube slowly enough that it dissolves by the time your glass is full. As the water mixes with the clear liquid it turns cloudy an effect called louching, caused by the oils in the absinthe. Finally, you stir the liquid with the spoon, and then drink."

Preparation of Absinthe by adding sugar & cold water. Image courtesy of Wikimedia, modified by W.P. Armstrong (2012).

1. 140 proof absinthe poured into bottom of glass. 2. Ice water poured over sugar cube, dissolving the sugar. 3. Full glass of water plus sweetened absinthe. My solution did not become as cloudy (milky) as the above Wikimedia image. The louching phenomenon is caused by thujone essential oils (terpenes) that come out of solution as the temperature and alcohol concentration drop forming an emulsion. In organic chemistry, this is called "oiling out."

At the 52nd annual meeting of the American Association for Clinical Chemistry in San Francisco, California, Dr. Paul Wolf of the University of California at San Diego presented some fascinating information about the glycoside digoxin and how it may have affected the creativity of Vicent van Gogh (1853-1890). According to Dr. Wolf, Van Gogh's epilepsy was treated with digoxin from the foxglove plant (Digitalis purpurea). His famous work, "The Starry Night" contains yellow circles around the stars, which are similar to visual problems described by patients with digoxin toxicity even today. Van Gogh also drank the liqueur absinthe on a regular basis. Absinthe is a green, bitter liqueur primarily flavored with wormwood (Artemisia absinthium), a European herbaceous perennial related to the native sagebrush species (Artemisia) of the western United States. Absinthe also contains thujone, a terpenoid component of many essential oils, including those found in Artemisia and the coniferous genus Thuja. Research has shown that thujone not only fuels creativity, but also that an overdose of the compound causes yellow-tinged vision (xanthopsia). Another species of wormwood (Artemisia maritima) contains santonin that was used as a treatment for intestinal worms. An overdose of santonin also results in chemically induced xanthopsia. Not everyone agrees that absinthe or digoxin toxicity may have contributed to van Gogh's increasing use of the color yellow in the last years of his life. Perhaps van Gogh may simply have loved the color yellow! Generally the effects of chemically-induced xanthopsia includes color vision rich in yellow but lacking blue. Many of Van Gogh's famous paintings contained the primary colors yellow and blue, and would not qualify as examples of xanthopsia. In fact, according to Dr. Wilfred Niels Arnold, the leading authority on van Gogh's illness, there is no evidence that van Gogh ever took the drug digitalis, and artist preference is still the best working hypothesis for the high yellow canvases. "Also, and more important in the present context, it is absurd to include digitalis poisoning in lists of possibilities to explain all his neurologic and psychotic problems that culminated in suicide."

According to Dr. W.N. Arnold, Professor of Biochemistry at University of Kansas Medical Center and author of Vincent van Gogh: Chemicals, Crises, and Creativity Birkhäuser, Boston (1992), the illness of Vincent van Gogh was much more complicated. Van Gogh suffered from acute intermittent porphyria (AIP). This debilitating genetic disease is characterized by excessive production of pophyrins due to the deficiency of a particular enzyme within the heme biosynthetic pathway. The word "porphyria" comes from the Greek "porphyrus," which means purple. People with AIP typically have urine that is red or purple. Another famous person whose madness was attributed to AIP was King George III of the United Kingdom. Elevated concentrations of porphyrins can lead to cutaneous photosensitivity and other neurological abnormalities, including psychoses, hallucinations, convulsions and paralyses. This disease can be exacerbated by maltnutrition and fasting with low-carbohydrate, low protein diets. There is substantial evidence that van Gogh developed an affinity for absinthe. He also took excessive doses of camphor oil to relieve insomnia. According to W.N. Arnold, van Gogh was abnormally sensitive to absinthe because of his congenital disease AIP. H.L. Bonkovsky and W.N. Arnold (1992) have shown that the terpenes camphor, thujone and pinene are porphyrogenic. "The combination of overexposure to camphor, absinthe abuse, and fasting or malnutrition would be injurious for anyone, but devastationg for someone with AIP." Dr. Arnold (2004) summarizes van Gogh in the following two sentences: "He was wonderfully creative because of intelligence, talent, and hard work. He was a genius in spite of his illness - not because of it."

Although they are not proteins, some respiratory pigments called porphyrins, such as the heme component of the red blood cell pigment hemoglobin, are associated with polypeptides. Porphyrins contain a complex nitrogenous ring with a metallic atom (iron, magnesium or copper) in the center. Plant pigments (chlorophylls a & b) are magnesium porphyrins. Some invertebrates with green blood have copper porphyrins. Porphyrins also include the iron-containing cytochrome pigments located on the inner membranes (cristae) of mitochondria in plants and animals.

  More Information About Porphyrins On Plant Chemistry Page  

Left: A molecule of hemoglobin composed of 4 amino acid chains (proteins): 2 alpha chains (red) and 2 beta chains (blue). Each chain also has an iron-containing heme group (green). This macromolecule carries oxygen to all tissues of the body. Right: the porphyrin heme, a component of the red blood pigment hemoglobin. Heme is a heterocyclic organic molecule containing one atom of iron in the center. Iron is the site of oxygen binding in a heme molecule. Each iron can bind one oxygen molecule, thus each hemoglobin is capapable of binding a total of four molecules of oxygen (O2). There are other examples of porphyrins in living systems. Heme & Hemoglobin images courtesy of Wikimedia Commons..

Vincent van Gogh died in 1890 and was burried in Auvers, France. In 1905 his remains were moved to a larger gravesite nearby. His casket had been completely entwined by the roots of an ornamental evergreen tree (Thuja occidentalis) that is a source of the terpenoid thujone. In fact, the name "thujone" is derived from the genus Thuja. It is interesting and ironic that Vincent van Gogh's relationship with thujone continued even after his death.

Addendum (Personal Communication 5 Nov 2020)

Researchers from The University Medical Center Groningen, in the Netherlands (2020), say that they believe Van Gogh experienced two brief psychotic episodes, presumed to be delirium caused by alcohol withdrawal, following his admission to hospital after cutting off his own ear with a razor in 1888. The experts believe the delirium was caused after the artist was forced to stop drinking alcohol after being admitted to hospital.

Thujone, Absinthe & Related References:

  1. Arnold W.N. 1992. Vincent van Gogh: Chemicals, Crises, and Creativity. Absinthe, Chapter 4, pp. 101-138. Birkhäuser, Boston, Mass.

  2. Arnold W.N. 1992. Vincent van Gogh: Chemicals, Crises, and Creativity. Afterword: Burial, reburial and the thuja tree. pp. 310-311. Birkhäuser, Boston, Mass.

  3. Arnold W.N. 2004. "The Illness of Vincent van Gogh." Journal of the History of Neurosciences. 13: 22-43.

  4. Arnold W.N. 1989. "Absinthe." Scientific American 260: 112-117.

  5. Arnold W.N. 1988. "Vincent van Gogh and the thujone connection." JAMA 260: 3042-3044.

  6. Arnold W.N, Dalton P.T, Loftus L.S and Conan P.A. 1991. "A search for santonin in Artemisia pontica, the other wormwood of old absinthe." J. Chem. Educ. 68: 27-28.

  7. Bonkovsky H.L., Cable E.E, Cable J.W, Donoghue S.E, White E.C, Greene Y.J, Lambrecht R.W, Srivastava K.K and Arnold W.N. 1992. "Porphyrogenic properties of the terpenes - camphor, pinene, and thujone: with a note on the illness of Vincent van Gogh." Biochem. Pharmacol. 43: 2359-2368.

  8. Hold K.M, Sirisoma N.S, Ikeda T., Narahashi T., Casida J.E. 2000. "Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification." Proc. Natl. Acad. Sci. U S A. 97: 3826-31 (2000).

Absinthe (Artemisia absinthium) growing at the Wayne's Word garden in San Diego County, California. Like many North American sagebrushes of the genus Artemisia, it has gray-green, aromatic foliage with deeply lobed leaves. The cooking herb called tarragon (A. dracunculus) also belongs to the genus Artemisia.

A closeup view of absinthe (Artemisia absinthium) showing the deeply lobed (pinnatifid) leaves. This aromatic perennial herb is related to the many sagebrush species of North America. It also belongs to the same genus as tarragon (A. dracunculus).

"The Yellow House" painted by Vincent van Gogh
 about two years before his death in the year 1890.
"Starry Night" painted by Vincent van Gogh
 while in an Asylum at Saint-Remy in 1889.

  See Photo Of The Closely-Related Herb Tarragon  

Dogbane Family (Apocynaceae)

The unusual flowers of Strophanthus speciosus have long, slender petals. This South African shrub has seeds that contain a potent cardiac glycoside called strophanthin. The ground seeds are used by native people to make a deadly poison for their arrow tips. Like digitalis, strophanthins are also used in modern medicine to treat congestive heart failure.

  Go To Glycosides In Plant Chemistry Article  

Nerium oleander, a commonly cultivated, drought resistant shrub in southern California. It is often planted as a screen along freeways, particularly in the center strip separating opposite lanes of traffic. Two of the most popular color variations are white and red. Cultivars called "doubles" with multiple petals (more than five) are also available.

Cerbera manghas, a southeast Asian tree introduced into several Polynesian Islands, including Hawaii. It is often planted for its very fragrant blossoms which resemble those of plumeria. The ripe fruits superficially resemble small mangoes in shape and size. The foliage and fruits contain the potent cardiac glycoside cerberin and are extremely poisonous if ingested.

The dried fruits (drupes) of Cerbera odollan, a large shrub or small tree native to muddy river deltas of southeast Asia and tropical Pacific Islands. The drupes are 2-4 inches (5-10 cm) in length. When they fall from the branches, the papery, outer exocarp withers away, exposing a thick fibrous husk (mesocarp). The fruits typically separate into two seed-bearing halves (lower left fruit). The fruits are very light and buoyant, and are dispersed by ocean currents. Because the seeds are not that well protected when the fruits split open, they probably could not survive long ocean voyages.

Madagascar periwinkle (Catharanthus roseus), source of the indole alkaloids, vinblastine and vincristine. These alkaloids are called spindle poisons, and they have proven to very effective in chemotherapy treatments for leukemia and Hodgkin's disease (lymph node and spleen cancer). They cause the dissolution (depolymerization) of protein microtubules which make up the mitotic spindle in dividing cells. This effectively stops the tumor cells from dividing, thus causing remission of the cancer. Before periwinkle alkaloids were used as a treatment there was virtually no hope for patients with Hodgkin's disease. Now there is a 90 percent chance of survival. This is a compelling reason for preserving the diverse flora and fauna in natural ecosystems. Who knows what cures for dreaded diseases are waiting to be discovered in tropical rain forests or other natural habitats.

  Go To Indole Alkaloids In Plant Chemistry Article  
See A Generalized Explanation Of Cell Division

Caribbean snakeroot (Rauvolfia viridis ), photographed on the island of St. John, U.S. Virgin Islands. [Note: The generic name is sometimes spelled Rauwolfia.] The indole alkaloid reserpine is derived from the roots of another species of snakeroot (Rauvolfia serpentina). Reserpine is chemically similar to serotonin, and has been used to stop the schizophrenia-like symptoms of LSD and as a brain depressant for schizophrenic patients. Although R. serpentina is native to India, other species of Rauvolfia (such as this one) may be potential sources of reserpine.

Another species of Rauvolfia (possibly Rauvolfia caffra) photographed in the Palomar College arboretum. [Note: The generic name is sometimes spelled Rauwolfia.] The indole alkaloid reserpine is derived from the roots of a different species of snakeroot (Rauvolfia serpentina). The lower leaf in photo contains scale insects that were protected by Argentine ants.

  Indole Alkaloids In Plant Chemistry Article  
Go To Article About Argentine Ants

Lily Family (Liliaceae)

The bulblike corm of autumn crocus (Colchicum autumnale), a member of the lily family (Liliaceae), contains colchicine, a 3-ring amine alkaloid. Like the anticancer indole alkaloids, vinblastine and vincristine, it is a spindle poison causing depolymerization of mitotic spindles into tubulin subunits. This effectively stops the tumor cells from dividing, thus causing remission of the cancer. Because colchicine can stop plant cells from dividing after the chromatids have separated during anaphase of mitosis, it is a powerful inducer of polyploidy. Seeds and meristematic buds can be treated with colchicine, and the cells inside become polyploid with multiple sets of chromosomes (more than the diploid number). Polyploidy in plants has some tremendous commercial applications because odd polyploids (such as 3n triploids) are sterile and seedless. Polyploid plants (such as 4n tetraploids) typically produce larger flowers and fruits. In fact, many of the fruits and vegetables sold at supermarkets are polyploid varieties. Colchicine has another medical use for people because it reduces the inflammation and pain of gout.

  Go To Amine Alkaloids In Plant Chemistry Article  
See A Generalized Explanation Of Cell Division

A gelatinous glycoside called aloin from the succulent leaves of some Mediterranean aloe species, particularly Aloe vera (A. barbadensis), has remarkable healing properties. It has been prescribed since ancient Greek times for a variety of ailments, including skin inflammation, ringworm, scabies and rashes. The soothing gel is applied topically to wounds and burns caused by fire, excessive exposure to sunlight and radiation. Aloe gel is also used in hemorrhoidal salves, shampoos, hair conditioners, hand lotions and many other products. The aloe species shown above is the African species, A. kedongensis.

Moonseed Family (Menispermaceae)

Curare (Chondodendron tomentosum), a South American vine native to the Amazon Basin. The undersides of the leaves are white-tomentose. An extract from the bark and stems is the source of a potent isoquinoline alkaloid used in the deadly poison curare. Amazonian Indians use the gummy extract to coat the poison darts of their blowguns. The alkaloid D-tubocurarine blocks acetylcholine receptor sites at neuromuscular junctions, causing relaxation and paralysis of muscles, including respiratory organs and the heart. In fact, D-tubocurarine has been used to relax the heart muscle during open heart surgery. It has also been used to treat the spastic paralysis of tetanus toxin from the bacterium Clostridium botulinum. Tetanus toxin causes uncontrollable muscle contraction throughout the body.

  Go To Isoquinoline Alkaloids In Plant Chemistry Article  
Go To The Deadliest Plant & Bacterial Toxins On Earth

Nighshade Family (Solanaceae)

An unidentified species of Brunfelsia, a genus of shrubs native to the Amazon Basin. Several species of this attractive shrub are cultivated in southern California, including varieties of B. pauciflora (B. calycina). They are called "yesterday-today-and-tomorrow" because the blossoms change from deep purple ("yesterday"), to lavender ("today"), and fade to white ("tomorrow"). In the Colombian, Ecuadorian and Peruvian Amazon, several species of Brunfelsia are used as hallucinogens. According to R.E. Schultes and A. Hofmann (Plants of the Gods, 1979), Brunfelsia is added to a hallucinogenic drink called Yajé made from the giant forest liana Banisteriopsis caapi (Malpighiaceae). Scopoletin has been isolated from Brunfelsia, but this may not be the only psychoactive compound present. Scopoletin is a phenolic lactone (C10H8O4) that is found in many solanaceous plants, including species of Scopolia and the deadly nightshade (Atropa belladonna). According to Schultes and Hofmann, a sensation of chills follows the ingestion of Brunfelsia, an effect which has given rise to the name "chiricaspi" or "cold tree".

Staff-Tree Family (Celastraceae)

Khat or bushman's tea (Catha edulis) is a shrub or small tree native from Arabia through eastern Africa to the Cape of South Africa. Small white flowers are produced in the axils of toothed, opposite leaves, followed by clusters of brown seed capsules. The generic name Catha is derived from "khat" the Arabic common name for this plant. The fresh leaves are chewed and made into a stimulant tea by Muslim people and by the Copts of Ethiopia. In fact, khat is widely cultivated on terraced hills in the highlands of eastern Ethiopia. Leaves contain the amine alkaloid cathinone, the effects of which are similar to amphetamine.

Khat (Catha edulis) showing clusters of seed capsules in leaf axilx.

The psychoactive chemicals in the leaves responsible for the human attraction to khat include two monamine alkaloids cathine and cathinone. Both alkaloids are the amine-type in which the nitrogen atom is not within a heterocyclic carbon ring. Instead, nitrogen is in a side chain that branches off from the carbon ring. This structure is also found in other psychoactive alkaloids, such as ephedrine and mescaline. Cathinone appears to be the primary stimulant in khat, and is chemically and psychoactively similar to amphetamine and methamphetamine. It is different from other amphetamines because it contains a ketone functional group (C=O) on the beta position of the side chain. The less powerful stimulant cathine has an alcohol functional group (C-OH) at this position. The decrease in potency of fresh khat leaves after several days is caused by the conversion (reduction) of cathinone into cathine. This is why fresh leaves are preferred. The legal status of khat is DEA Schedule I, CA Schedule III, and UK Class A.

Growth habit and basal trunks of Khat (Catha edulis).

The interaction of khat alkaloids on the human nervous system is complex and is similar to the stimulatory effects of amphetamines. In fact, amphetamine is prescribed for the treatment of narcolepsy and attention deficit hyperactivity disorder (NDHD). The effects of chewing fresh leaves includes general euphoria and increased alertness, accompanied by relief from hunger and fatigue. Like South America coca leaves, the drug gives a constant mild high to those who chew leaves throughout the day. A Google search on the Internet will produce a world of articles about this fascinating plant.

Seed capsule and small winged seeds of khat (Catha edulis). The average
length of one individual seed is approximately 6.5 mm, including the wing.

  Amine Alkaloids Without Heterocylic Nitrogen  

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