One of the most common groups of chemicals that has medicinal properties found in plants is the alkaloids1. Alkaloids are natural substances that react like bases – like alkalis – and they are bitter, probably to make the plant less palatable to herbivores2 (see the previous section). Alkaloid concentrations are often highest in the most vulnerable tissues or the outermost parts of the plant, such as the external layers of the bark, stems, roots, or the seed tegument3. Figure 2 shows the chemical structure of some common alkaloids and the plants from which they are obtained. Notice in each example, that the alkaloid contains a nitrogen atom, which provides the basic character (i.e., the N atom can bind to additional H atoms). Although included here, THC is not an alkaloid. It does not have any N atoms, but instead it has a multi-carbon chain that gives it an oily character. Similarly, lipids contain chains of C atoms, providing their hydrophobic4 (water-fearing) or oily character.
Figure 2 The chemical structure is shown for several alkaloids found in plants. Alkaloids contain a nitrogen atom, which gives the compound a basic nature. THC is not an alkaloid – note that it doesn’t contain a N atom.
Alkaloids are found typically in flowering plants called angiosperms5. Angiosperms, defined as “seed in a vessel,” are a type of vascular plant with its seed enclosed by an ovary wall. Angiosperms are one the most successful land plants and they produce much of our food, as well as many of our psychoactive6 drugs7. About 10-15 percent of Angiosperms produce alkaloids. The Angiosperms can be sub-divided into monocots8 and dicots9. Monocots have embryos bearing only one seed leaf (known as a cotyledon10); they have parallel-veined leaves, 3-petaled (or multiples of 3) flowers, and scattered vascular bundles that run through out the plant (examples include corn, grains, lilies, irises, and grasses). The vascular bundles contain cell structures called xylem11, which transports water and salts, and phloem12, which transports sugars and other metabolites13. Non-vascular plants lack water- and food-conducting tissues, so they do not have true leaves, stems, and roots–e.g. mosses, liverworts, and hornworts. An example of a monocot is shown in Figure 3. This monocot is called Dioscorea, or the wild yam. The compounds of interest found in this plant (and others in the Dioscorea genus) include diosgenin, a steroid-like compound that provides the starting material to make progesterone used in birth-control pills. In fact, if it weren’t for the Mexican yam, there would be a severe shortage of birth-control pills!
Figure 3 The leaf and flower of a monocot (left – Dioscorea or the wild yam) is compared to a dicot (right – palaver somniferum or opium poppy). Dicots, but not monocots, contain alkaloids.
In contrast, dicots have embryos bearing two cotyledons, net-veined leaves, 4- or 5-petaled flowers, and vascular cylinders arranged in concentric rings within the plant stem (examples include woody or herbaceous plants such as oak, apple and cherry trees, potatoes, tomatoes, and cacti). In Figure 3, an example of a dicot is shown – the opium poppy. Also referred to as a eudicot, the opium poppy’s leaf looks more like a monocot. Alkaloids are found more commonly in the dicots, although monocots contain many compounds that have poisonous qualities.
Alkaloids are synthesized at a specific site in a plant such as the growing root, laticiferous cells14, and chloroplasts15. After they are synthesized, the alkaloids are transported to a storage site, usually a vacuole16 located in the cytoplasm of the cell (Figure 4). Vacuoles are bubble-like compartments that are surrounded by membranes. Vacuoles are a prominent feature of plant cells and often become very large, occupying up to 90% of the total volume of a plant cell. These structures contain a watery solution called “cell sap”, consisting of a variety of nutrients and waste. Many compounds, including amino acids, sugars, and alkaloids are dissolved in the cell sap of the vacuole. The watery environment of the vacuole enables the storage of compounds that are dissolved in water.
Figure 4 The basic structure of a plant cell includes a large vacuole. The vacuoles contain alkaloids dissolved in an acidic environment. Modified from: micro.magnet.fsu.edu/cells/plantcell.html
Alkaloids can exist in both a water-soluble (polar17 or charged) form and in a more lipid-soluble (non-polar18 or uncharged) form, depending on the pH of the environment. The equilibrium reaction showing the conversion of an alkaloid such as cocaine from the polar to the non-polar form in an aqueous medium depending on the pH is shown in Figure 5 (also see Module 1). Because the pH within the vacuole is relatively acidic, the excess of H atoms will shift the equilibrium to more polar form; the alkaloid will gain H atoms (they form bonds with the N) and it becomes charged or polar. (If the vacuole pH were more basic, the alkaloid would be more non-polar (uncharged or lipophilic19) and it would not be able to be dissolved well in the water milieu of the vacuole.)
Figure 5 Treating the cocaine free base with HCl generates the charged form of cocaine, or the ‘acid salt’. Conversely, treating the acid salt with a base such as sodium bicarbonate (baking soda) yields the free base form of cocaine.
There are several other groups of compounds in plants that have medicinal properties. These include glycosides, saponins (soap-like steroids20), and oils. A famous glycoside is digitalis (or digoxin), found in the foxglove plant. It is still used today in the treatment of heart arrythmias and congestive heart failure. Salicylates (the precursor to aspirin), from the bark of the willow tree, are aromatic acids. Salicylates themselves can reduce acne due to their anti-inflammatory properties. Look at the label of your acne products and you might find it! THC (its medicinal use is hotly debated), obtained from the cannabis plant, is an oil – it is very lipid soluble. The non-polar character makes it easy to smoke; it can be heated to a high temperature to volatilize without destroying the molecule. See the next section for more discussion about its volatility.
Definitions:
1 an organic compound of natural origin. Alkaloids contain a nitrogen atom and are usually basic. Most alkaloids have marked pharmacological properties.
2 an organism that feeds on plants.
3 a natural outer covering.
4 “water-fearing”; a compound that is soluble in fat but not water. This is typical of compounds with chains of C atoms.
5 a type of flowering vascular plant that has water- and food-conducting tissues. Its seed is enclosed by an ovary wall. Angiosperms include the monocots and dicots.
6 pertains to drugs that act in the brain to produce changes in mood, perceptions, and behavior.
7 a substance that affects the structure or function of a cell or organism.
8 type of angiosperm defined by flowering plants with embryos having a single cotelydon, parallel-veined leaves, 3-petaled flowers, and scattered vascular bundles.
9 type of angiosperm defined by flowering plants with embryos having two cotelydons, net-veined leaves, 4- or 5-petaled flowers, and concentric vascular cylinders.
10 the primary leaves of an embryo that are present in the seed (also known as a seed leaf). It is a stored food source for the embryo.
11 tissue in vascular plants that is responsible for the transport of water and salts.
12 tissue in vascular plants that is responsible for the transport of sugar and other metabolites.
13 usually an inactive form of a drug or other substance that is more polar (charged) than the parent compound. Drugs are metabolized by enzymes primarily in the liver.
14 secretory cells.
15 a specialized organelle in green algae and plants that contains chlorophyll (a light absorbing pigment) It performs photosynthesis.
16 a sac-like compartment in a plant cell that stores alkaloids. It is responsible for “holding” various nutrients and wastes, as well as dissolving amino acids and sugars.
17 a chemical property of a substance that indicates an uneven distribution of charge within the molecule. A polar substance or drug mixes well with water but not with organic solvents and lipids. Polar or charged compounds do not cross cell membranes (lipid) very easily.
18 a chemical property of a substance that indicates an even distribution of charge within the molecule. A non-polar or non-charged compound mixes well with organic solvents and lipids but not with water.
19 high lipid solubility. Lipophilic compounds dissolve readily in oil or organic solvent. They exist in an uncharged or non-polar form and cross biological membranes very easily.
20 a class of hormones synthesized from cholesterol by specific cells in the body. They are powerful compounds that alter genetic function, causing numerous effects in the body.
