Terpenoids are synthesized via the mevalonate and deoxyxylulose pathways with the use of a five-carbon building block known as isoprene. This family of constituents has many different members, each with five more carbons than the last as another isoprene is added (Types of Terpenoids).

Types of Terpenoids
Terpenoid Class Basic Structure Number of Isoprene Units Miscellaneous Notes
Monoterpenoid C10H16 2 Usually volatile
Iridoid C10H16 (bicyclic) 2 Subclass of monoterpenoids
Sesquiterpenoid C15H24 3 Usually volatile
Sesquiterpene lactone C15H24 (cyclic ketone) 3 Subclass of sesquiterpenoids
Diterpenoid C20H32 4 Not usually volatile. Often in resins
Triterpenoid C30H48 6 Nonvolatile
Tetraterpenoid (carotenoid) C40H64 8 Nonvolatile
Polyterpenoids >C40 10+ Nonvolatile

Monoterpenoids, made up of two isoprene units, are the smallest and simplest type of terpenoids (Select Low-Molecular-Weight Terpenoid-Rich Herbs). They are of sufficiently low molecular weight that they tend to volatilize readily. Their close cousins are the sesquiterpenoids, with three isoprene units. They are also of sufficiently light molecular weight as to be volatile. Monoterpenoids and sesquiterpenoids are referred to as low-molecular-weight terpenoids (LMWT). Low-molecular-weight terpenoids are generally found only in vascular plants, although occasionally, they may occur in simpler organisms and in some insects.

Select Low-Molecular-Weight Terpenoid-Rich Herbs
Monoterpenoids and Sesquiterpenoids
Hyssopus vulgaris (hyssop)
Juniperus communis (juniper)
Lavandula officinalis (lavender)
Melissa officinalis (lemon balm)
Mentha x piperita (peppermint)
Mentha crispa (curly mint)
Mentha pulegium (pennyroyal)
Mentha spicata (spearmint)
Origanum spp (marjoram, basil)
Orthosiphon stamineus (Java tea)
Pinus spp (pine)
Piper nigrum (black pepper)
Rosmarinus officinalis (rosemary)
Salvia apiana (white sage)
Salvia officinalis (sage)
Santalum albium (sandalwood)*
Stachys betonica (betony)
Thymus serpyllum (wild thyme)
Thymus vulgaris (thyme)
Zingiber officinale (ginger)
Sesquiterpene Lactones
Achillea millefolium (yarrow)
Arnica spp (arnica)
Artemisia annua (sweet Annie)
Artemisia absinthium (wormwood)
Cichorium intybus (chicory)
Ginkgo biloba (ginkgo)
Inula helenium (elecampane)
Lactuca serriola (wild lettuce)
Marrubium vulgare (horehound)
Tanacetum parthenium (feverfew)
Iridoid Glycosides
Erythraea centaurium (common centaury)
Centiana lutea (yellow gentian)
Harpagophytum procumbens (devil’s claw)
Menyanthes trifoliata (bogbean)
Morinda citrifolia (noni)
Picrorhiza kurroa (picrorhiza)
Plantago lanceolata (English plantain)
Swertia chirayita (chiretta)
Verbena spp (vervain)
*Threatened in the wild. Use only ethically cultivated sources.

Although they are synthetically and structurally distinct, phenylpropanoids have most of the same properties as low-molecular-weight terpenoids. Phenylpropanoids are synthesized via the shikimic acid pathway by way of cinnamic acid. This category of constituents, based on a nine-carbon skeleton, is not as diverse as low-molecular-weight terpenoids. All statements that follow here about low-molecular-weight terpenoids terpenoids apply equally to phenyl-propanoids. However, phenylpropanoids are much less common than low-molecular-weight terpenoids (Select Phenylpropanoid-Rich Herbs).

Select Phenylpropanoid-Rich Herbs
Acorus calamus (sweet flag)
Alpinia galanga (galangal)
Cinnamomum spp (cinnamon, cassia)
Eleutherococcus senticosis (eleuthero)
Foeniculum vulgare (fennel)
Melissa officinalis (lemon balm)
Nigella sativa (black seed)
Ocimum basilicum (basil)
Pimpinella anisum (anise)
Rhodiola rosea (rhodiola)
Sassafras albidum (sassafras)
Syzygium aromaticum (clove)

Low-molecular-weight terpenoids represent the most diverse category of plant constituents, with more than 25,000 individual compounds identified so far. This structural diversity gives rise to chemical and therapeutic variety. Generalizations about their actions are not as useful as with some other categories of constituents.

The vast majority of low-molecular-weight terpenoids and phenylpropanoids share many chemical properties. They are lipophilic with marginal water solubility. They generally have strong odors and flavors and, in fact, form the basis of the flavor and perfume industries. The family best known for its low-molecular-weight terpenoids is the Lamiaceae or mints, with its strong aromas and tastes. Low-molecular-weight terpenoids are flammable. Many are optically active, and different isomers can have completely different properties. They are almost always colorless.

The medicinal properties of low-molecular-weight terpenoids are nearly as diverse as the molecules themselves. A small sampling will suffice to highlight this variability. D-Limonene sol-ubilizes cholesterol from bile stones and has recently gained great acclaim as an antineoplastic and apoptosis stimulator, which it accomplishes through mechanisms that are not yet fully understood. Menthol is a calcium channel-blocking smooth muscle relaxant. Linalool, cineole, geraniol, menthol, and citral were found to be antibacterial and antifungal to varying degrees.

Iridoids are cyclic monoterpenoids that are almost uniformally bitter in taste. They often occur as glycosides. Their bitter flavor makes them general gastrointestinal stimulants. A quintessential example of a bitter iridoid glycoside-containing plant is Gentiana lutea (gentian) root. This can help remedy any number of conditions related to gastrointestinal atony such as gastric ulcer, dyspepsia, and hypochlorhydria, but it may exacerbate conditions associated with gastrointestinal hyperactivity such as duodenal ulcer, gastroesophageal reflux, and hyperchlorhydria. Iridoids can have other properties besides bitterness.

Sesquiterpene lactones are cyclic sesquiterpenoids that have a bitter flavor and activity, as iridoids do. A quintessential example here is the compound absinthin found in Artemisia absinthium (wormwood). Sesquiterpene lactones can also have many other properties, and these have been widely investigated. Most important among these is the antineoplastic and antimalarial activity of artemisinin from Artemisia annua (sweet Annie) leaf. Sesquiterpene lactones in general can act as haptens and are responsible for the phenomenon in some animals of cross-sensitivity within the Apiaceae or Asteraceae family, as opposed to true allergies to multiple plants within these families.

The phenylpropanoids are as diverse in their effects as are low-molecular-weight terpenoids. Eugenol has recently been shown to be a potent inhibitor of metastasis of melanoma cells and to strongly induce apoptosis in them, apparently through inhibition of a transcription factor dubbed E2F1. It also inhibits adenosine triphosphate (ATP) production and may alter membrane permeability in many different pathogenic microbes, which helps to explain the antimicrobial activity of eugenol-rich herbs. Vanillin is a singlet oxygen-quenching antioxidant.

Low-molecular-weight terpenoids and phenylpropanoids are well absorbed orally and transdermally. Evidence also suggests that they are absorbed via the olfactory nerve and transit directly to the brain after inhalation. After oral administration, the half-lives of those low-molecular-weight terpenoids that have been studied, such as menthol, can be as long as 14 hours. This is not surprising, given their lipophilicity. LMWT and phenylpropanoids are excreted by the kidneys, as well as the lungs, making them particularly useful for conditions that affect those organs.

Low-molecular-weight terpenoids and phenylpropanoids occur in very small quantities in herbs (often <1%) and are not usually associated with any toxicity. The only problem with their use occurs when they are concentrated as volatile oils.

Volatile or essential oils are traditionally prepared from herbs by steam distillation or, in the case of Citrus spp (e.g., orange), by direct expression. Steam distillation was first developed by the Arabs approximately 1000 years ago; thus, volatile oils have been known for only that long. These oils are extremely concentrated mixtures of multiple low-molecular-weight terpenoids and phenylpropanoids (depending on the herb in question). In the case of steam-distilled volatile oils, compounds are often chemically different from those found in the crude herb because of their exposure to heat. A classic example is the formation of chamazulene, a light blue sesquiterpenoid lactone not present in the crude herb, from matricin during steam distillation of Matricaria recutita (chamomile) flowers.

A newer type of volatile oil has also become available over the past few years; it is extracted with the use of supercritical carbon dioxide. Because no heat is needed in this process, the volatile oils produced are not the same as steam-distilled volatile oils, although they are the same as those oils obtained by expression. These extracts are certainly safer and superior to various volatile oils and related products (e.g., resinoids, concretes, absolutes) obtained by means of a variety of toxic organic solvents. Their relative activity compared with steam-distilled volatile oils is largely unknown because of a lack of comparative research and a very short clinical track record.

Volatile oils have the same properties as low-molecular-weight terpenoids and phenylpropanoids because they are composed entirely of them. However, the concentration of these compounds is increased hundreds or thousands of times, greatly amplifying their potency and toxic potential compared to the crude plant material. All volatile oils must be treated as potentially lethal and administered only in low doses. They are readily absorbed through the skin and after ingestion. Depending on the individual and the concentration applied, they can cause cutaneous inflammation and sensitization. Partially for this reason and because of expense, volatile oils are almost always diluted at least 50% with fixed oils (fatty acids) before application.