Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer.
This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans.
Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments.
This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage.
Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualities for future crop production are discussed.
For humans, lettuce and chicory (Lactuca sativa and Chicorium intybus L.) represent the major dietary sources of the sesquiterpene lactone. The benefits of eating fruits and vegetables as part of a healthy diet are widely known, and although statistics vary greatly between studies.
In addition to vegetables, beverages can also contribute to sesquiterpene consumption, with chicory root being used to make tea and sometimes used as a coffee substitute.
In addition, some Asteraceous plants are used to reduce the bitterness of some alcoholic beverages. Other sources of sesquiterpenoids include spices, such as anise and herbs, although their consumption is understandably smaller. Traditional medicinal plants can also be a significant source for some populations, as sesquiterpenoids often represent the active ingredient. These medicinal plants usually belong to the Asteraceae family, of which “malaria” (Tanacetum parthenium (L.) Sch. Bip.) Yarrow (Achillia spp.), and quinghaosu (A. annua) in the treatment of malaria, is among the most commonly used both historically and in current alternative treatments.
Sesquiterpenes là hợp chất ưa béo không màu. Quá trình sinh tổng hợp ở thực vật là từ ba đơn vị isoprene. Sesquiterpenes bao gồm 15 carbon xương sống, và trong khi cấu trúc của chúng đa dạng, phần lớn và các dạng chức năng nhất là chu kỳ, và do đó trọng tâm của bài tổng quan này sẽ dựa vào các hợp chất này.
Sesquiterpenes are colorless lipophilic compounds. Biosynthesis in plants is from three isoprene units, and occurs via farnesyl pyrophosphate (FPP), in the endoplasmic reticulum. Sesquiterpenes consist of a 15 carbon backbone, and whilst diverse in their structure, the majority, and the most functional forms are cyclic, and consequently the focus of this review will rest upon these compounds.
The large number of sesquiterpene synthases coupled with the fact that a single synthase may produce numerous products and further modifications after sesquiterpene synthesis, such as oxidation and glycosylation take place, result in a vast number of varied structures, many similar synthases may produce the same products, in different ratios which affect the metabolite profile of a plant and can be used to classify closely related species or subspecies.
Regulation of the pathways is highly controlled in some species where sesquiterpenes are produced as a stress response, Aquilaria sinensis (Lour.) produces sesquiterpenes only in response to herbivory, and 26 unigenes coding seven enzymes have been characterized. Oxidation of the 3C side chain of germacranolides is responsible for the formation of the lactone ring in germacranolides type sesquiterpenes, and guaianolides and eudesmanolides are further derived from this.
Biosynthesis of sesquiterpene lactones is highly characterized, with detailed reports available amongst others. Germacranolides, guaianolides, pseudoguianolides and eudesmanolides (Figure 1) are the most representative classes, germacranolides being the most significant with regards to their function in humans. Eudesmanolides (Figure 1A,B) have two fused 6 membered rings: germacranolides have a 10 membered ring; (Figure 1C,D): Guaianolides (Figure 1E–H) have a 7-membered and a 5-membered ring, and a methyl group at C-4: Pseudoguaianolides (Figure 1I–N) have a 7-membered and a 5-membered ring and a methyl group at C-5. All contain a fused 5-membered lactone group (γ lactone) with a carbonyl moiety at the alpha position.
Eudesmanolides α-santonin (A), β-santonin (B), germacranolides; Parthenolide (C), Lactuside A (D), guaianolides; 8-deoxylactucin (E), 11.(S),3-dihydrolactucopicrin (F), lactucin (G), lactucopicrin (H), Pseudoguaianolides; helenalin (I), Hymenin (J), lettucenin A (K), parthenin (L), tenulin (M), Strigolactones; 8-deoxy-strigol (N) Cadinanolide; Artemisinin (O), Seco-cadinanolide; Artemisinic acid (P)
Pharmacological effects of sesquiterpene
1. Inhibits cancerous tumor growth and induces cytotoxicity
According to studies on plant-based compounds with anti-cancer properties, scientists have discovered that sesquiterpenes are on the list of such substances. According to studies, there are about 50 types of sesquiterpenes evaluated to have the ability to inhibit the growth of tumors in experimental models.
Scientists have found that all types of sesquiterpenes that are potentially cytotoxic to cancer contain lactone function, with the exception of sesquiterpenes that contain double bonds at the α, β and α-ethylenic positions.
In a further study of the mechanism of action and structure relationship between sesquiterpene lactones, it was noted that the presence of an extracyclic double bond at the C11–C13 position is essential. essential for cytotoxicity of cancer cells.
One of the typical sesquiterpenes in fighting cancer cells is parthenolide. This active ingredient has been studied and used a lot in Europe in the treatment of cancer.
Parthenolide’s mechanism of action may be due to: stimulation of the natural apoptosis process of cancer cells (apoptosis), inhibition of NF activity – kappa B.
2. Antibacterial, inhibits the growth of fungus
According to the researchers, this antibacterial activity has been reported in several plant species containing high levels of sesquiterpenes.
These sesquiterpenes have been shown to inhibit the growth of:
- Staphylococcus aureus, Escherichia coli.
- Candida albicans và some worms.
And two sesquiterpenes have been isolated that show strong antibacterial effects: tanachin and tavulin. However, the inhibitory effect of tavulin was weaker than that of tanachin.
Besides, some types of serquiterpenes also have the ability to fight viruses, such as the well-known active ingredient such as artemisinin isolated from the plant. This active ingredient is commonly used in the treatment of dengue fever caused by the dengue virus.
Not only that, but some active ingredients that are semi-synthetic from artemisinin such as artesunate also work against some viruses such as:
- HCMV (human cytomegalovirus).
- Herpes simplex virus type – 1 (HSV – 1).
- Epstein – Barr virus
3. Has anti-inflammatory properties
According to experts, sesquiterpenes have the ability to regulate a number of inflammatory processes, such as phosphorylation, platelet aggregation, histamine and seretonin release.
However, the main inflammatory response inhibited by sesquiterpenes involves nuclear factor-kappa B (NF-κB). A comprehensive study by Bork et al showed that 54 Indian and Mexican medicinal plants, all rich in Sesquiterpene lactones, had potent inhibitory effects on the NF-κB pathway.
NF-κB is a family of proteins that control DNA transcription, cytokine production, and cell survival. The proteins form heterozygous or homozygous cytoplasmic complexes consisting of p50 and p65 subunits.
A comprehensive study by Siedle et al. described 103 sesquiterpenes from 6 subclasses that inhibit NF-κB DNA binding.
Not only that, they found that the majority of sesquiterpenes with this activity belonged to the guaianolide subgroup and that the presence of an unsaturated carbonyl group played a major role in cytotoxicity.
Typical for sesquiterpenes with anti-inflammatory activity among these compounds are zerumbone and parthenolide.
4. Antioxidant activity
Sesquiterpen lactone group is considered a group of substances with very strong antioxidant activity. Researchers Ruberto and Baratta looked at the lipid-oxidizing capacity of a wide range of plant essential oil components and found that sesquiterpenes have stronger oxidizing activity due to the presence of the allylic alcohol component.
In addition, scientists also put forward the view that thanks to strong antioxidant properties, the sesquiterpen group has the ability to inhibit the growth of tumors through affecting the process of spontaneous apoptosis. nature of cancer cells.
Hopefully, the information that the article has shared has helped you gain more important knowledge about sesquiterpenes and the benefits of this active ingredient to human health.
Wish you always healthy and happy in life.
This article is for informational purposes only and is not a substitute for medical diagnosis or treatment.