Revisiting the Medicinal Value of Terpenes and Terpenoids

Abstract

Nowadays, plant-based chemicals have drawn the attention of pharmacy researchers due to their potent biological activity against various ailments. In this series, terpenes and terpenoids are gaining popularity among drug researchers gradually. Terpenes are naturally occurring large and varied class of hydrocarbons substances produced by a wide variety of plants including fruits, vegetables, flowers and some animals. Their concentration is generally high in plants. A broad range of the biological properties of terpenoids includes cancer chemo-preventive effects, antimicrobial, antifungal, antiviral, anti-hyperglycemic, anti-inflammatory, anti-parasitic activities and memory enhancers. Terpenoids are usually cyclic unsaturated hydrocarbons, with the altered number of oxygen moieties in the constituent groups attached to the basic isoprene skeleton. Terpenoids are a group of substances that occur in nearly every natural food. Terpenoids display a wide range of biological activities against cancer, malaria, inflammation, tuberculosis and a variety of infectious diseases including viral as well as bacterial. In this chapter, we have emphasized the proven and expected medicinal value of both terpenes and terpenoids.

1. Introduction

The role of fruits and vegetables in human nutrition and public health is taken into account in most nutritional recommendations. Fruit and vegetables contain an abundance of various natural compounds that have been associated with the protection and treatment of many ailments.

Terpenes are a huge and diverse category of natural compounds, obtained from a variety of plants, especially conifers, which are characteristic smelling and, in this manner, might have had a defensive function. They are the significant parts of resin and turpentine obtained from the resin. Terpenes are major biosynthetic basic compounds inside every living being. At the point when terpenes are altered chemically, i.e., by oxidation or reframing of the carbon skeleton, the subsequent mixtures are by and large alluded to as terpenoids [1].

As natural substances, terpenoids are broadly consumed in food, pharmaceuticals, and beauty care products ventures. Indeed, terpenoids are used for the counteraction and treatment of different diseases. Likewise, many investigations have additionally found that terpenoids have numerous expected applications to uncover [2]. This chapter contains updated information about the structure and diverse effects of terpenes and terpenoids.

2. Chemistry and occurrence

Plant biomass is a major potential sustainable source of organic carbon. Terpenes, terpenoids and resin acids are a group of non-polar molecules and share a building block, isoprene or isoprenoid [3], as a common elementary unit (Figure 1).

Figure 1.

Structure of isoprene unit [4].

Isoprene, the epitomic terpene substance, is one of the most plentifully ethereal hydrocarbon compounds on Earth attributable to the worldwide plenitude of terpenoid biosynthesis, not the other way around. Around 40% of the biogenic volatile natural compounds transmitted by plants are isoprene, and isoprene is the key hydrocarbon distinguished in human breath. Film crowds breathe out more isoprene when watching scenes of anticipation [5].

Based on ancient scientifically verified data, it is found that the expressions “isoprenoid” and “terpenoid” are applied conversely and that there is still no worldwide accord on terminology.

For instance, a few researchers have named “terpene” to allude just to hydrocarbons dependent on an indispensable number of C5 units, and “terpenoid” or “isoprenoid” to assign the entire class of compound dependent on an intrinsic number of C5 units [6].

Such compounds can be in every way called “terpenes,” and the expression “terpenoid” ought to be held for compounds, for example, the steroids, which have differing quantities of carbon molecules, however, are originated from a (C5)n structure [7]. Ruzicka considered this multitude of compounds aggregately to be “terpenic” [8]. Nes and McKean employed the expression “isoprenoid” to portray the entire group [9].

Different classes along with carbon units of terpenes and terpenoids are depicted in Figure 2.

Figure 2.

Classification of terpenes and terpenoids.

Terpenes are significant elements of natural oils, which are secondary metabolites synthesized for battling infectious or secreted because of stress conditions. These are extricated from different fragrant plants commonly limited in mild to warm climatic regions like the Mediterranean and tropical nations where they represent a significant piece of the conventional pharmacopeia. They are ethereal, fluid, transparent, and seldom colored, lipid-dissolvable, and dissolvable in natural solvents with a by and large lower thickness than water. They can be isolated from all plant organs, for example, blossoms, buds, leaves, twigs, stems, seeds, roots, wood, fruits or bark, and are accumulated in secretory cells, holes, trenches, glandular trichomes, or epidermic cells [10].

2.1 Monoterpene

The smallest of terpenes are monoterpenes (Figure 3). They contain the compound C₁₀H₁₆, come from different flowers, fruits and leaves and are known as the main component of essential oils, fragrances and many structural isomers [11]. Monoterpenes are found in natural scents for example α-pinene, which imparts scent to pine trees [12], and limonene from citrus plants [13]. One of the main purposes of monoterpenes is to attract pollinators or to serve the purpose of repelling other organisms from feeding off of plants [14].

Figure 3.

Sub-classes of monoterpenes with structural example.

2.2 Sesquiterpene

Sesquiterpenes, containing the chemical formula C₁₅H₂₄ (Figure 4), are much larger compounds than monoterpenes and are much more stable in comparison [15]. Sesquiterpenes are naturally occurring and found in plants, fungi, and insects and act as a defensive mechanism or attract mates with pheromones in insects [16].

Figure 4.

Classification of sesquiterpenes with structural example.

Gossypol is a sesquiterpene that is present in cotton plants. It has anti-neoplastic properties and might hinder fertility in male people that is the reason it should be taken out from natural oils and different items before human application [17]. Avarol, a sesquiterpenoid that has been displayed to have antifungal and antimicrobial effects, is compelling against AIDS infection [18].

2.3 Diterpene

Diterpenes are natural substances that contain the atomic skeleton, C20H32 (Figure 5) [19]. Diterpenes have physiologically dynamic compounds, for example, plant development chemicals that manage germination, blooming, switch regenerative cycles (from abiogenetic to sexual multiplication) of plants, and vitamin A activity [20]. Cafestol and kahweol are diterpene alcohols that are found in the oil derived from coffee beans [21].

Figure 5.

Sub-classes of diterpenes with structural example.

2.4 Triterpene

Triterpenes are composed of three or six isoprene units and have the chemical formula C₃₀H₄₈ (Figure 6) which includes steroids and sterols with squalene being the biological precursor of all Triterpenes [22]. Triterpenes are produced by animals, plants, and fungi. They play a role as precursors to steroids in animal and plant organisms, and are derived from mevalonic acid [5].

Figure 6.

Classification of Triterpenes.

Their properties have been studied for anticancer, antioxidant, antiviral, and anti-atherosclerotic activities [23]. Although, the medicinal uses of tri-terpenes are not quite as recognized as other different types of terpenes but their uses are being continuously investigated by researchers.

2.5 Tetraterpene

Tetraterpenes are also known as carotenoids (Figure 7) that have the molecular formula C₄₀H₅₆ and can be in the category of terpenes because they are made from isoprene units [24]. They are found in all different types of fungi, bacteria, and plants and are mainly responsible for red, yellow, or orange fat-soluble plant and animal pigments [25]. One of the most crucial and common tetraterpenes is beta-carotene [26].

Figure 7.

Structural example of tetraterpene.

3. Plants with terpenoids

Terpenoids, or isoprenoids, are isoprene-based compounds with major jobs in the digestion of all living beings [27]. Varieties of terpenoids are particularly high in plants where many can be viewed as secondary metabolites. Such specific plant terpenoids underlie numerous natural co-operations between plants, creatures, and microorganisms (Tables 1–4) [38], going about as allele-synthetics to repulse herbivores, tempt pollinators, or allure herbivore hunters [39]. The development of terpenoids in plants started with the enrollment of genes from primary metabolism and sped up because of the multiplication of cytochrome P450 and terpene synthase gene families in the genomes of plants [40].

Class	Plant source
Monoterpenes	Mentha genus, Cannabis spp.
Sesquiterpenes	Artemisia annua L., Thapsia garganica,
Diterpenes	Taxus brevifolia, Ricinus communis, Euphorbia peplus,
Triterpenes	Azadirachta indica, Khaya grandifolia, Trichilia emetic, Citrus reticulate
Tetraterpenes	Mauritia flexuosa, Brassica oleracea, Crocus sativum L.

Table 1.

List of some plants contains terpenes and terpenoids [28, 29, 30, 31].

Class	Insect source
Monoterpene	Philonthus politus, Zygaena filipendulae, Ips pini
Sesquiterpene	Harmonia axyridis, Murgantia histrionica, Myzus persicae

Table 2.

List of some animals contains terpenes and terpenoids [31, 32, 33].

Class	Fungal source
Monoterpenes	Aspergillus versicolor, Eutypella scoparia, Gelliodes carnosa, Trichoderma asperellum, Thielavia hyalocarpa, Aeromonas hydrophilia, Vibrio anguillarum
Sesquiterpenes	Aspergillus fumigatus, Pterocladiella capillacea, Cochliobolus lunatus, Paraconiothyrium sporulosum, Penicillium griseofulvum, Pseudallescheria apiosperma,
Diterpenes	Acremonium striatisporum, Aspergillus wentii, Curvularia hawaiiensis, Penicillium commune, Talaromyces; purpurogenus, Trichoderma harzianum,
Triterpenes	Auxarthron reticulatum,

Table 3.

List of some fungi contains terpenes and terpenoids [34, 35].

Class	Bacterial source
Sesquiterpenoids	Streptomyces strain M491
Diterpenoids	Streptomyces strain CNB-982, Streptomyces sioyaensis, Verrucosispora gifhornensis YM28–088,
Meroterpenoids	Actinomycete isolates CNH- 099, Erythrobacter sp. strain SNB- 035, Saccharomonos; pora sp. CNQ- 490

Table 4.

List of some bacteria contains terpenes and terpenoids [36, 37].

Terpenoid compounds partly mirrors a characteristic history set apart by herbivory stress and other particular tensions forced by creatures, bringing about a wide cluster of functionalized terpenoids in the plant realm pre-chosen for their strong organic activities towards animals [41]. This specific cycle might have been brought about by the overall closeness of protein structures and amino acid sequence among plant and creature proteins, bringing about planting auxiliary metabolites with a natural resemblance for creature proteins by ethicalness of having been delivered by plant bio-catalyst made out of similar amino acids [32].

Terpenoids are dependent on the tetracyclic 6–6–6-5 lanostane carbon skeleton structure a subsection of the terpenome known as the sterolome. The sterolome is assessed to contain about 1000 biogenic derivatives obtained from lanosterol and related particles that do fundamental organic functions across all areas of life on Earth [42].

Many plant terpenoids have been tracked down coincidentally uses in medication and the terpenoids family has been an important wellspring of clinical revelations. However, the testing system is meticulous and asset concentrated. The genuine number of plants terpenoids in nature that might be evaluated for therapeutic applications is obscure however is possibly more than 105, including more than 12,000 from the diterpenoid specifically [43]. While this number is little contrasted with current combinatorial techniques, the lead compound disclosure rate might be altogether higher for plant-based compounds. It is due to a crucial role in chemical, and metabolic processes, many are produced in limited quantities, only in response to a stimulus, or amass solely in particular tissues, requiring microbial multiplication or significant advances by plant rearing and hereditary improvement to get adequate amounts to research clinical benefits [44, 45].

4. Medicinal importance

Terpenoids have an expansive group of clinical activities (Figure 8) and are spread everywhere, they have been utilized in conventional medications for ancient times. Numerous compounds can be found commercially, majorly as dietary enhancements; nonetheless, some of them are enrolled as medications.

Figure 8.

Reported and traditional therapeutic application of terpenes and terpenoids.

4.1 Anti- insect activity

Human wellbeing and crop cultivation are mainly affected by insects, and trying to control these bugs the application of chemical bug sprays has become broad. Notwithstanding, this has brought about the improvement of obstruction in these living creatures, human infections, tainting of food, and contamination of the climate. Herbs and medicinal oils like terpenes and terpenoids have been displayed to have a huge potential for bug control like carvacrol, limonene, linalool, 1, 8 cineole, eugenol, and β-ionone; especially against three insects namely lice, cockroaches, and Triatominae bugs [46, 47, 48].

4.2 Anti-microbial activity

Antimicrobial properties or the capacity to kill or stop the development of a microorganism in terpenes are normally utilized in customary and current day medication. The accompanying plants produce terpenes that have antimicrobial potential: Pinusponderosa (Pinaceae), flavors (cumin, rosemary, thyme, caraway, clove, and sage), Cretan propolis, Helichrysumitalicum, Rosmarinus officinalis, etc. [49].

There are 52 anti-microbial terpenoids, including hydrocarbons of the oil; aromadendrene (4.4%), limonene (3.8%), α-cedrene (9.6%), β-caryophyllene (4.2%), and α-pinene (10.2%), geranyl acetic acid derivation (4.7%), 2-methylcyclohexyl pentanoate (8.3%), 2-methylcyclohexyl octanoate (4.8%), and neryl acetic acid derivation (11.5%) etc. [50, 51].

4.3 Anti- plasmodial activity

Terpenes have been shown to have a favorable anti-plasmodial activity. With the rising malarial infections and drug resistance, terpenes have gained more attention towards it through anti-plasmodial activity. Terpenes have been shown to have a favorable anti-plasmodial activity. With the rising malarial infections and drug resistance, terpenes have gained more attention towards it through anti-plasmodial activity. Different kinds of terpenes show different effects on the parasites. The most common terpenes with anti-plasmodial potential are Beta-myrcene limonene, pinene, caryophyllene, etc. Thus, terpenes could be a safer and a cost-effective alternative for malarial treatment [52, 53].

4.4 Anti-cancer activity

Cancer-related observational studies propose that dietary monoterpenes might be useful in the anticipation and treatment of malignant growths. Among dietary monoterpenes, D-limonene and perillyl alcohol have been displayed to have chemo-preventive and health beneficial properties against numerous human malignant growths. At present they are professed to inhibit fraction-dependent proliferation of skin, lung, mammary, liver, colon, prostate, pancreatic, and stomach carcinomas [54, 55].

4.5 Anti-viral activity

Presently, the antiviral potential of terpenoids is somewhat ineffectively perceived. Consequently, there is a ton of exploration pointed towards finding agents, likewise from natural sources, which could have intense antiviral potential. The new antiviral compounds ought to explicitly restrain the virus and ought not to affect the healthy biological environment of the cell. The quest for natural antiviral moieties has paved the way for the extraction of isoborneol. Potent anti- herpes simplex virus −1 (anti-HSV-1) activities have also been reported for monoterpenes such as cineol and borneol [56, 57].

4.6 Anti-hyperglycemic activity

Type 2 diabetes mellitus is a chronic metabolic disorder that results from reduced first-phase insulin secretion. Stevioside is a diterpene steviol glycoside extracted from leaves of the plant Stevia rebaudiana, which possesses insulinotropic, glucagonostatic, and anti-hyperglycemic effects [58, 59].

4.7 Anti-inflammatory activity

(−)-linalool, a naturally occurring enantiomer, possesses anti-inflammatory activity. Moreover, (−)-linalool and its ester, linalyl acetate, demonstrated analgesic and edema reducing effects [60, 61, 62].

4.8 Anti-malarial activity

Artemisinin (sesquiterpene lactone) is secluded from Artemisia annua Linn. It is the best antimalarial drug after pyrimethamine, chloroquine, and primaquine, and has the attributes of a high therapeutic index. Afterward, antimalarial medications, for example, artesunate, arteether, and artemether have been isolated by altering the chemistry of artemisinin. Nirolidol likewise has ant-malarial activity [63, 64].

4.9 Cardio-protective activity

Finding a powerful boon for treating the cardiovascular problems is a pressing objective for researchers. Tanshinone IIA (TS) is a functioning moiety separated from the rhizome of Chinese home-grown medication Salvia miltiorrhiza Bunge. The most recent discoveries recommend that TS can forestall the emergence of atherosclerosis and the harm and hypertrophy of the heart [65, 66].

4.10 Anti-tubercular activity

Tuberculosis is a very fatal disease to mankind and still the treatment regimen and new drug discovery attract the researchers to reveal a new paradigm in medical science. For the first time, diterpenoid of isosteviol, its binuclear derivatives, tri-terpenoid betulinic, oleanolic, and ursolic acids have been reported to possess anti-tubercular activity, manifested by the molecular docking method. Other natural constituents of the class are Geranylgeraniol, phytanol, escobarine A, escobarine B, furanoditerpenes, salasol A, germacrane, alantolactone, etc. [67, 68].

5. Conclusion

As of now, the clinically evident method of therapeutic activity of numerous terpenoids has not still been clarified. Besides, a relationship of “omics” technology and sub-atomic network pharmacology can be utilized to further affirm the mechanism and structural activity relationship (SAR) of terpenoids. Such study will be a promising step in the development of new medication substances thusly; the compounds with higher interest might be swiftly advanced into new medications, or structurally modified as lead compounds. It is a significant method for the innovative work and development of the medication, and it is additionally a hot spot in the subject of natural product studies. At present, reported terpenoids are about 50,000 inescapable among living beings and major fractions of them are obtained from plants. A few terpenoids are industrially notable for their dietary or therapeutic significance. The new dosage type of terpenoids might be advanced in a blend with the new techniques of pharmaceutics to expand its pharmacological activity. As more terpenoid-based clinical medications will open up, they will assume a vital part in human ailment therapy in forthcoming years. Or terpenoids might be acquainted as additives substances with wellness care items and beauty care products, which has immense market possibilities and money-related benefits. We are completely persuaded that it is the beginning stage for the fate of new green science, in light of terpenes and medicinal oils between scientists, industry, and academics.