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While sometimes used interchangeably with "terpenes", terpenoids have additional functional groups, usually containing oxygen.[1] Terpenoids are the largest class of plant secondary metabolites, representing about 60% of known natural products.[2] Many terpenoids have substantial pharmacological bioactivity and are therefore of interest to medicinal chemists.[3] Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, the yellow color in sunflowers, and the red color in tomatoes.[4]

Def. "a very large class of naturally occurring and synthetic organic compounds formally derived from the hydrocarbon isoprene; they include many volatile compounds used in perfume and food flavours, turpentine, the steroids, the carotene pigments and rubber"[5] is called a terpenoid.

Classification[edit | edit source]

Terpenoids Analogue terpenes Number of isoprene units Number of carbon atoms General formula Examples[6]
Hemiterpenoids Isoprene 1 5 C5H8 Dimethylallyl pyrophosphate (DMAPP), isopentenyl pyrophosphate, isoprenol, isovaleramide, isovaleric acid, (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), prenol
Monoterpenoids Monoterpenes 2 10 C10H16 Bornyl acetate, camphor, carvone, citral, citronellal, citronellol, geraniol, eucalyptol, hinokitiol, iridoids, linalool, menthol, thymol
Sesquiterpenoids Sesquiterpenes 3 15 C15H24 Farnesol, geosmin, humulone
Diterpenoids Diterpenes 4 20 C20H32 Abietic acid, ginkgolides, paclitaxel, retinol, salvinorin A, sclareol, steviol
Sesterterpenoids Sesterterpenes 5 25 C25H40 Andrastin A, manoalide
Triterpenoids Triterpenes 6 30 C30H48 Amyrin, betulinic acid, limonoids, oleanolic acid, sterols, squalene, ursolic acid
Tetraterpenoids Tetraterpenes 8 40 C40H64 Carotenoids
Polyterpenoid Polyterpenes >8 >40 (C5H8)n Gutta-percha, natural rubber

Cyclicity[edit | edit source]

Terpenoids can also be classified according to the type and number of cyclic structures they contain: linear, acyclic, monocyclic, bicyclic, tricyclic, tetracyclic, pentacyclic, or macrocyclic.[6] The Salkowski test can be used to identify the presence of terpenoids.[7]

Hemiterpenoids[edit | edit source]

Carotenes[edit | edit source]


Carotene (also carotin, from the Latin carota, "carrot"[8][9]) is used for many related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but in general cannot be made by animals (with the exception of some aphids and spider mites which acquired the synthesizing genes from fungi).[10]

Pure carnivores such as ferrets lack β-carotene 15,15'-monooxygenase and cannot convert any carotenoids to retinals at all (resulting in carotenes not being a form of vitamin A for this species); while cats can convert a trace of β-carotene to retinol, although the amount is totally insufficient for meeting their daily retinol needs.[11]

The following foods contain carotenes in appreciable amounts:[12]

Absorption from these foods is enhanced if eaten with fats, as carotenes are fat soluble, and if the food is cooked for a few minutes until the plant cell wall splits and the color is released into any liquid.[12] 12 μg of dietary β-carotene supplies the equivalent of 1 μg of retinol, and 24 µg of α-carotene or β-cryptoxanthin provides the equivalent of 1 µg of retinol.[12][14]

Carotenes include cryptoxanthin, lutein and zeaxanthin.

beta-Carotenes[edit | edit source]

Structure diagram shows beta-carotene. Credit: NEUROtiker.{{free media}}
β-Carotene powder is shown. Credit: 102% Yield.{{free media}}

β-Carotene is an organic, strongly coloured red-orange pigment abundant in fungi,[17] plants, and fruits. β-Carotene is biosynthesized from geranylgeranyl pyrophosphate.[18]

In some Mucorales (Mucoralean) fungi, β-Carotene is a precursor to the synthesis of trisporic acid.[17]

β-Carotene, the most common form of carotene in plants when used as a food coloring, has the E number E160a.[19] The structure was deduced by Karrer et al. in 1930.[20] In nature, β-carotene is a precursor (inactive form) to vitamin A via the action of beta-carotene 15,15'-monooxygenase.[18]

Isolation of β-carotene from fruits abundant in carotenoids is commonly done using column chromatography. It can also be extracted from the beta-carotene rich algae, Dunaliella salina.[21] The separation of β-carotene from the mixture of other carotenoids is based on the polarity of a compound. β-Carotene is a non-polar compound, so it is separated with a non-polar solvent such as hexane.[22] Being highly conjugated, it is deeply colored, and as a hydrocarbon lacking functional groups, it is very lipophilic.

Plant carotenoids are the primary dietary source of provitamin A worldwide, with β-carotene as the best-known provitamin A carotenoid. Others include alpha-Carotene (α-carotene) and cryptoxanthin (β-cryptoxanthin). Carotenoid absorption is restricted to the duodenum of the small intestine and dependent on class B scavenger receptor (SR-B1) membrane protein, which is also responsible for the absorption of vitamin E (α-tocopherol).[23] One molecule of β-carotene can be cleaved by the intestinal enzyme β,β-carotene 15,15'-monooxygenase into two molecules of vitamin A.[24]

Factors that determine the provitamin A activity of carotenoids:[25]

  • Species of carotene
  • Molecular linkage
  • Amount in the meal
  • Matrix properties
  • Effectors
  • Nutrient status
  • Genetics
  • Host specificity
  • Interactions between factors

Monoterpenoids[edit | edit source]

Lemon balm[edit | edit source]

Lemon balm flavor comes from geraniol (3–40%), neral (3–35%), geranial (4–85%) (both isomers of citral), (E)-caryophyllene (0–14%), and citronellal (1–44%).[26]

Lemon balm contains eugenol, tannins, and terpenes.[27] It also contains (+)-citronellal, 1-octen-3-ol, 10-α-cadinol, 3-octanol, 3-octanone, α-cubebene, α-humulene, β-bourbonene, caffeic acid, caryophyllene, caryophyllene oxide, catechin, chlorogenic acid, cis-3-hexenol, cis-ocimene, citral A, citral B, copaene, δ-cadinene, eugenyl acetate, γ-cadinene, geranial, geraniol, geranyl acetate, germacrene D, isogeranial, linalool, luteolin-7-glucoside, methylheptenone, neral, nerol, octyl benzoate, oleanolic acid, pomolic acid, ((1R)-hydroxyursolic acid), protocatechuic acid, hamnazin, rosmarinic acid, stachyose, succinic acid, thymol, trans-ocimene and ursolic acid.[28][29] Lemon balm may contain traces of harmine.[30]

Rosmarinic acid appears to be the most important active component, but the interaction of the chemicals in lemon balm and herbs that it is used with, is poorly understood.[31] Lemon balm leaf contains 36.5 ± 0.8 mg rosmarinic acid per gram.[32]

Composition of lemon balm oil[33]
Component minimum % maximum %
Methyl Heptenone 2.2 8.6
Citronellal 1.0 8.4
Linalool 0.5 2.7
Neral 19.6 36.1
Geranial 25.3 47.5
Geranyl acetate 1.2 6.2
Carophyllene 1.9 9.7
Carophyllene oxide 0.5 9.0

Iridoids[edit | edit source]

Valepotriates: isovaltrate and valtrate are in Valerian.[34]

Terpineol[edit | edit source]

Terpineols: alpha-, beta-, gamma-, and the 4-terpineol isomer. Credit: V8rik.{{free media}}

Terpineol is any of four isomeric monoterpenoids. Terpenoids are terpene that are modified by the addition of a functional group, in this case, an alcohol. Terpineols have been isolated from a variety of sources such as cardamom, cajuput oil, pine oil, and petitgrain oil.[35] Four isomers exist: α-, β-, γ-terpineol, and terpinen-4-ol. β- and γ-terpineol differ only by the location of the double bond. Terpineol is usually a mixture of these isomers with α-terpineol as the major constituent.

Sesquiterpenoids[edit | edit source]

Helenalin[edit | edit source]

Diagram is a skeletal formula of helenalin. Credit: Fvasconcellos.{{free media}}

Helenalin, or (-)-4-Hydroxy-4a,8-dimethyl-3,3a,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione, is a toxic sesquiterpene lactone which can be found in several plants such as Arnica montana and Arnica chamissonis subsp. foliosa. Helenalin is responsible for the toxicity of the Arnica spp. Although toxic, helenalin possesses some in vitro anti-inflammatory and anti-neoplastic effects. Helenalin can inhibit certain enzymes, such as 5-lipoxygenase and leukotriene C4 synthase. For this reason the compound or its derivatives may have potential medical applications.[36][37]

Helenalin can target the p65 subunit (also called RelA) of the transcription factor NF-κB. It can react with Cysteine Cys38 in RelA by Michael addition. Both reactive groups, α-methylene-γ-butyrolactone and cyclopentene, can react with this cysteine.[38] It was also found that helenalin can inhibit human telomerase, a ribonucleoprotein complex, by Michael addition. In this case also, both reactive groups of helenalin can interact with the thiol group of a cysteine and inhibit the telomerase activity.[39] Helenalin inhibits the formation of leukotrienes in human blood cells by inhibiting LTC4 synthase activity. Helenalin reacts with its cyclopentenone ring to the thiol group of the synthase.[37]

Helenalin inhibits cytochrome P450 enzymes by reacting with thiol groups, resulting in inhibition of the mixed-function oxidase system. These effects are important for the cytotoxicity of helenalin. The levels of glutathione, which contains sulfhydryl groups, are reduced in helenaline-treated cells, further increasing the toxicity of helenalin. Depending on the dose of helenalin, thiol-bearing compounds such as glutathione may provide some protection to cells from helenalin toxicity. It was also seen that helenalin increase CPK and LDH activities in serum and that it inhibits multiple enzymes of the liver involved in triglyceride synthesis. Therefore, helenaline causes acute liver toxicity, accompanied by a decrease cholesterol levels.[40]

Helenalin also suppresses essential immune functions, such as those mediated by activated CD4+ T-cells, by multiple mechanisms.[41]

Helenalin and some of its derivatives have been shown to have potent anti-inflammatory and anti-neoplastic effects in vitro. Some studies have suggested that the inhibition by helenalin of platelet leukotriene C4 synthase, telomerase activity and transcription factor NF-κB contributes to helenalin's in vitro anti-inflammatory and anti-neoplastic activity[37][39][42] .[43][44] The dose used varied per study. There is currently no in vivo evidence regarding helenalin's anti-inflammatory and anti-tumour effects, if any. The efficacy of helenalin for treatment of pain and swelling, when applied topically, is not supported by the current available evidence at doses of 10% or lower. For doses higher that 10%, more research is required whether those remain safe and are more efficient than the current available medications.[45]

Plant extracts containing helenalin were used as a herbal medicine for the treatment of sprains, blood clots, muscle strain and rheumatic complaints.[41] Currently helenalin is used topically in homeopathic gels and microemulsions. Helenalin is not Food and Drug Administration (FDA)-approved for medical application.[46]

When applied topically on humans, helenalin can cause contact dermatitis in sensitive individuals. However, it is considered generally safe when applied this way. Oral administration of large doses of helenalin can cause gastroenteritis, muscle paralysis, and Cardiotoxicity (cardiac) and Hepatotoxicity (liver damage). The toxicity of helenalin was studied in mammalian species such as mice, rat, rabbit and sheep, were the oral Median lethal dose (LD50) of helenalin was established between 85 and 150 mg/kg.[47][48] It was shown in a mouse model that helenalin caused reduced levels of cholesterol. In a rat model, alcohol hepatic injury was prevented by helenalin administration.[40][49] Parenteral administration showed a higher toxic effect when compared to oral administration.[50][51]

Helenalin has a variety of observed effects in vitro including anti-inflammatory and antitumour activities.[52] Helenalin has been shown to selectively inhibit the transcription factor NF-κB, which plays a key role in regulating immune response, through a unique mechanism.[53] In vitro, it is also a potent, selective inhibitor of human telomerase[39]—which may partially account for its antitumor effects—has anti-trypanosomal activity,[54][55] and is toxic to Plasmodium falciparum.[56]

Animal and in vitro studies have also suggested that helenalin can reduce the growth of Staphylococcus aureus and reduce the severity of S. aureus infection.[57]

Sesquiterpenes[edit | edit source]

Valerian contains in the volatile oil: valerenic acid,[58] hydroxyvalerenic acid and acetoxyvalerenic acid[59]

Diterpenoids[edit | edit source]

Sesterterpenoids[edit | edit source]

Triterpenoids[edit | edit source]

Diagram illustrates the chemical structure of quassin. Credit: Walkerma.
Diagram illustrates the chemical structure of the prototypical limonoid limonin. Credit: Fvasconcellos.

Centella contains pentacyclic triterpenoids, including asiaticoside, brahmoside, asiatic acid, and brahmic acid (madecassic acid), where other constituents include centellose, centelloside, and madecassoside.[60][61][62]

Centella asiatica, commonly known as Gotu Kola, kodavan, Indian pennywort and Asiatic pennywort, is a herbaceous, perennial plant in the flowering plant family Apiaceae.[63] It is native to the wetlands in Asia.[64][65] It is used as a culinary vegetable and as a medicinal herb.[63]

Eurycoma longifolia, commonly known as Tongkat Ali, has been reported to contain the glycoprotein compounds eurycomanol, eurycomanone, and eurycomalactone.[66] Eurycomanone has been isolated from Eurycoma longifolia, also known as the longjack plant or tongkat ali.[67]

Quassinoids are degraded triterpene lactones (similar to limonoids) of the Simaroubaceae plant family grouped into C-18, C-19, C-20, C-22 and C-25 types.[68] The prototypical member of the group, quassin, was first described in the 19th century from plants of the genus Quassia from which it gets its name.[69] It was isolated in 1937[70] and its structure elucidated in 1961.

Quassinoids are a biologically potent class of natural products, possessing antimalarial,[71] antifeedant,[72] insecticidal,[73] anti-inflammatory,[74] and anticancer[75] properties. The quassinoid bruceantin reached two separate phase II clinical trials in 1982[76] and 1983.[77]

Other quassinoids include:[78]

  • Bruceanols
  • Bruceolide
  • Eurycomanone
  • Gutolactone
  • Isobrucein A
  • Neoquassin
  • Nigakihemiacetal A
  • Quassimarin
  • Samaderines
  • Simalikalactones

Limonoids are triterpenoids which abundant in sweet or sour-scented citrus fruit and other plants of the families Cucurbitaceae, Rutaceae, and Meliaceae.[79] Certain limonoids are antifeedants such as azadirachtin from the neem tree.[80]

Chemically, the limonoids consist of variations of the furanolactone core structure. The prototypical structure consists of four six-membered rings and a furan ring. Limonoids are classed as tetranortriterpenes.

Citrus fruits contain the limonoids limonin, nomilin and nomilinic acid, while both neem seeds and leaves contain the limonoid azadirachtin, although higher concentrations are present in the former.

Boswellic acids[edit | edit source]

Structure of α-boswellic acid is diagrammed. Credit: Fvasconcellos.{{free media}}
Daigram shows structure of β-boswellic acid. Credit: Fvasconcellos.{{free media}}
Structure of 11-keto-β-boswellic acid is shown. Credit: Fvasconcellos.{{free media}}

Boswellic acids are a series of pentacyclic terpenoid molecules that are produced by plants in the genus Boswellia. Like many other terpenes, boswellic acids appear in the resin of the plant that exudes them; it is estimated that they make up 30% of the resin of Boswellia serrata.[81] While boswellic acids are a major component of the resin, the steam or hydro distilled frankincense essential oil does not contain any boswellic acid as these components are non-volatile and too large to come over in the steam distillation process (the essential oil is composed mainly of the much lighter monoterpene and sesquiterpene molecules with small amounts of diterpenoid components being the upper limit in terms of molecular weight).[82][83][84] Boswellic acids are organic acids, consisting of a pentacyclic triterpene, a carboxyl group and at least one other functional group. Alpha-boswellic acid and beta-boswellic acid, C30H48O3 both have an additional hydroxyl group; they differ only in their triterpene structure. Acetyl-alpha-boswellic acid and acetyl-beta-boswellic acid, C32H50O4, replace the hydroxyl group with an acetyl group.

Beta-boswellic acid, keto-beta-boswellic acid, and acetyl-keto-beta-boswellic acid (AKBA) have been indicated in apoptosis of cancer cells, in particular brain tumors and cells affected by leukemia or colon cancer.[85]

Acetyl-boswellic acids also exhibit anti-inflammatory behaviour by inhibiting leukotriene synthesis.[86] It inhibits the activity of the enzyme Arachidonate 5-lipoxygenase (5-lipoxygenase) through a non-redox reaction. Specifically the 3-acetyl-11-keto-beta-boswellic acid binds as an allosteric partial inhibitor, initiating a shift in regioselectivity of the catalyzed reation.[87] Clinical trials[88][89] have investigated the effectiveness of boswellic acids in treating ulcerative colitis, but a study on chemically induced colitis in mouse models[90] showed little effectiveness. A latter study showed that low doses of Boswellia serrata extract may have hepatoprotective effects. The higher dose was found to have a milder hepatoprotective effect than the lower dose.[91]

Boswellic acids are also thought to decrease the symptoms of asthma; a small 1998 placebo-controlled trial of Boswellia extract for the treatment of asthma showed good results.[92] Boswellia extracts are sold in tablet, capsule and tincture form, but no dosage guidelines have been developed. The risk of hepatotoxicity due to Boswellia administration has not been assessed.

Tetraterpenoids[edit | edit source]

Polyterpenoids[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

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