Bluebell: Hyacinthoides non-scripta

[This post features my original artwork and botanical sketches]

I truly believe that revising for my upcoming exams and developing my understanding of the sciences is an enjoyable process, but when gentle dawn sunlight illuminates the vibrant azure bundles of flowers peppered throughout our garden, it takes the strength of every fibre in my being to not abandon my textbooks and immerse myself in the carpet of wild bluebells.

In two months, I’ll have sat all my AS exams and will finally be free to laze around in the grass with my cat and lie among the sea of indigo petals. Until then, I look to the shimmering haze of the bluebells as an oasis just fingertips away.

Recently, I rewarded my revision efforts by pressing an inflorescence and uncovering the chemistry behind their beautiful blue pigment*. The rich colour of the petals is not caused by a single true blue pigment but rather by the red pigment anthocyanin. The basic structure of the anthocyanin delphinidin is modified with pH shifts and prosthtic groups.

Delphinidin is pH sensitive and turns red in acidic environments. A high pH must be maintained to ensure the molecular pigment is blue. Delphinidin is also malonated; two glucosyl groups, a malonyl group, and a coumaryl group are bonded to the pigment structure. 

 

 

 

 

 

The resulting compound, malonylawobanin, is responsible for the brilliant deep blue petals that don’t even fade after weeks of pressing. 

I also consulted my copy of The Complete Herbal out of interest in the medicinal properties of this plant. Nicholas Culpeper was surprisingly brief in his writings of bluebells; he only refers to its somewhat styptic (blood clotting) qualities. From further research, I learnt that the bluebell’s intensely toxic nature has, understandably, limited its potential for therapeutic applications.

One of the major toxic compounds present in bluebells are polyhydroxylated pyrrolidines (such as nectrisine) which are found in the viscous sap that seeps out of the plant’s nodding stems. These compounds are analogues of sugar but are actually potent glucosidase inhibitors. Due to its many -OH groups, the mammalian body mistakes nectrisine as a sugar and processes it as such – inadvertantly allowing the molecule to interfere with respiration.

In addition to this, polyhydroxylated pyrrolizidines, which have a similar chemical action to nectrisine, are toxic alkaloids that have been proven to poison livestock that have the misfortune of ingesting bluebells. Despite this, these compounds are now being considered for use in cancer therapeutics.

Most fascinatingly, bluebells contain a type of cardiac glycoside, Scillaren A, which can rapidly increase the output force of the heart. Heart cells, myocytes, contain protein pumps embedded in their cell membranes which actively transport sodium ions out of the cell to create an essential electrochemical gradient. In the heart, there is also a sodium – calcium ion exchanger which maintains the ion homeostasis. 

Cardiac glycosides, such as Scillaren A found in bluebells, inhibit the movement of sodium ions out of the cell by effectively disabling the ion pumps. This increases the concentration of sodium ions inside the myocytes which, in turn, increases the calcium ion concentration as sodium ions inside the cell are exchanged for calcium ions.

In myocytes, the accumulation of calcium increases the power with which the cells can contract (contractility) – increasing cardiac muscle contraction which can be crucial in controlling the heart rate in cases of arrhythmia and even chemically restarting the heart in atrial fibrillation.

The cardiac action of Scillaren A is stronger than that of the commonly used digoxin, which is derived from foxglove, and is ideal for situations in which digoxin alone is insufficient or the patient has a digitalis intolerance. Additionally, if an improper dosage is administered, Scillaren A is poisonous but, unlike many other cardiac glucosides, is non-lethal as it is poorly absorbed into the gut. The compound also has a very high therapeutic index as it is rapidly eliminated from the body. All of these qualities make bluebells a fundamentally desirable pharmaceutical source, however, since native bluebells are an endangered and protected species, bluebells cannot be harvested to produce medication.

Conservation efforts are essential to protect and preserve this fragile, flowering species so that we may be able to enjoy their magnificent appearance and benefit from their therapeutic value in the coming decades.

 

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* White bluebells which lack pigmentation also exist albeit they are somewhat rare with only 1 in every 1000 native bluebells being white. Below is a pressed white bluebell I came across in Margate. 

Toxicology Thursday: Cyanide

Cyanide, a deadly compound found in bitter almonds and apple seeds, consists of simply two atoms (Carbon and Nitrogen) bonded together as a unit. Cyanide is typically found in ionic compounds where it is bonded to one other positive ion (a cation); hydrogen cyanide and potassium cyanide are notorious examples.

The toxicity of cyanide depends on how easily the bond between the cyanide unit and the cation can be broken. For instance, in hydrogen cyanide, the bond between the H⁺ and the cyanide unit are easily broken so hydrogen cyanide is extremely toxic.

When cyanide enters the bloodstream, it attaches to the iron in haemoglobin – displacing oxygen. Once bonded to haemoglobin, cyanide can travel rapidly around the body and reach the mitochondria of the cells. Within the mitochondria, cyanide can bind irreversibly to cytochrome c oxidase (an important respiration enzyme) – preventing energy from being released into the cell and, eventually, killing the cell.

Toxicology Thursday: Opiates

Opium refers to the crude extract obtained from poppy plants. Opium itself is fairly easy to obtain directly from poppies but its effects on the body are rather mild in contrast to other modified forms of opium. Opium has been modified into several, more potent drugs known as opiates; most notably, these are morphine, codeine, and heroin.

Morphine was the first developed opiate; it is named after Morpheus (the Greek god of dreams) for it’s ability to put the user to sleep or even in a coma.

Codeine is the second most abundant alkaloid found in opium. To work in the body, enzymes must first convert codeine into morphine- codeine therefore is slower-acting and much less addictive.

Heroin (also known as diamorphine) is a modified form of morphine with two acetyl groups. The acetyl groups increase the compound’s solubility in fats meaning it can pass through the blood-brain barrier very easily, allowing it to interact directly with the opioid receptors in the brain- making it far more potent and addictive.

The greatest medical benefit  of opiates is that they provide pain-relief. However, there is a darker side to the relaxed state such drugs can put you in; in the case of an overdose, the sedation deepens rapidly into a coma and the respiration rate drops substantially since opiates reduce the sensitivity of the respirator centre. Eventually, the respiratory failure leads to death.

Toxicology Thursday: Digitalis

Digitalis is a very effective poison given that it is readily available and lethal in very small quantities. But before you start plotting the demise of your enemies, it is worth noting that digitalis is also detectable in very small quantities.

Digitalis refers to compounds extracted from foxgloves which have specific and dramatic effects on the heart . Digitoxin is one such compound ; it has a serious effect on the heart because of its ability to dampen the electrical signals that coordinate the contractions of the cardiac muscles. In low doses, this causes arrhythmia (an irregular heart beat). However, in higher doses, digitoxin can completely block electrical signalling – effectively paralysing the heart.

Interestingly enough, atropine (a different toxin) can be given to stimulate the heart and work as an antidote to digitoxin poisoning or overdose.

Toxicology Thursday: Eserine

The Calabar bean is a natural sources of poison with a rich cultural history.

In Nigeria, in the early 19th century, there was a practice of feeding a paste of these poisonous beans to people accused of witchcraft, murder, or rape. If the person on trial died from poisoning, they were guilty and, if they survived, they were innocent.

Contrary to popular belief, there may be more logic behind this judicial system than initially meets the eye; guilty defendants would be more cautious or fearful about being exposed and so might be inclined to swallow the paste more slowly than an innocent. A slow administration of the poison allows for a longer exposure time increasing the absorption of the poison and, hence, worsening its effects. If this notion was true in every case, in general, innocent defendants would become quite ill but guilty defendants would most likely die.

The active agent of Calabar beans is physostigimine (also known as eserine); this toxin also disrupts the parasympathetic nervous system but in a different manner to atropine.

Acetylcholine (an important neurotransmitter) must be broken down after it performs its task- otherwise, the neurotransmitter would keep activating receptors and produce unwanted effects in the body. Eserine inhibits the enzyme that breaks down acetylcholine – producing opposite (yet equally extreme) effects to atropine poisoning. Whilst atropine dilates the pupils, eserine constricts them. Similarly, whilst atropine causes heart palpitations ands a rapid pulse, eserine poisoning results in heart paralysis.