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Molecules (Basel, Switzerland) Feb 2022Sesquiterpene lactones (SL), characterized by their high prevalence in the family, are one of the major groups of secondary metabolites found in plants. Researchers... (Review)
Review
Sesquiterpene lactones (SL), characterized by their high prevalence in the family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure-activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure-activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.
Topics: Animals; Anti-Inflammatory Agents; Asteraceae; Drug Discovery; Humans; Immunomodulating Agents; Lactones; Sesquiterpenes
PubMed: 35164406
DOI: 10.3390/molecules27031142 -
Computational and Mathematical Methods... 2022Applied science nowadays works on the isolation and application of biological macromolecules (BMM). These BMM are isolates from plants using different techniques and... (Review)
Review
Applied science nowadays works on the isolation and application of biological macromolecules (BMM). These BMM are isolates from plants using different techniques and used as anticancer, antimicrobial, and anti-inflammatory drugs. Parthenolide (PLT) is one of the most important biological macromolecules and a naturally occurring sesquiterpene lactone that is isolated from a plant species (). The anti-cancer and anti-inflammatory effects of PTL isolated from . were previously reported and summarized in detail. These biological activities make it a vital candidate for further researches and drugs development. As per the previously obtained findings, the sesquiterpene is very much known for some biological activities; therefore, the anti-cancer and anti-inflammatory activities of the sesquiterpene were critically reviewed. During the research process, PTL was found to be unstable in both acidic and basic conditions with low solubility, so structurally related compounds micheliolide (MCL) and Dimethylaminomicheliolide (DMAMCL) (a prodrug of MCL) were developed. In this article, we briefly review the therapeutic effects of PTL and its derivative DMAPT on inflammatory diseases and tumors, focusing on the current application of PTL in targeted therapy and combination therapy, together with anti-inflammatory and anti-tumor functions of MCL and DMAMCL. The uniqueness of this biological macromolecule is not to harm the normal cell but target the cancerous cells. Therefore, the current literature review might be helpful and useful for prospects based on the effects of MCL and DMAMCL on cancer.
Topics: Anti-Inflammatory Agents; Humans; Lactones; Neoplasms; Sesquiterpenes; Sesquiterpenes, Guaiane
PubMed: 35898475
DOI: 10.1155/2022/3744837 -
Science China. Life Sciences Feb 2016Sesquiterpenoids are a class of 15-carbon secondary metabolites that play diverse roles in plant adaptation to environment. Cotton plants accumulate a large amount of... (Review)
Review
Sesquiterpenoids are a class of 15-carbon secondary metabolites that play diverse roles in plant adaptation to environment. Cotton plants accumulate a large amount of sesquiterpene aldehydes (including gossypol) as phytoalexins against pathogens and herbivores. They are stored in pigment glands of aerial organs and in epidermal layers of roots. Several enzymes of gossypol biosynthesis pathway have been characterized, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and farnesyl diphosphate synthase (FPS) that catalyze the formation of the precursor farnesyl diphosphate (FPP), (+)-δ-cadinene synthase (CDN) which is the first enzyme committed to gossypol biosynthesis, and the downstream enzymes of CYP706B1 and methyltransferase. Expressions of these genes are tightly regulated during cotton plants development and induced by jasmonate and fungi elicitors. The transcription factor GaWRKY1 has been shown to be involved in gossypol pathway regulation. Recent development of new genomic platforms and methods and releases of diploid and tetraploid cotton genome sequences will greatly facilitate the elucidation of gossypol biosynthetic pathway and its regulation.
Topics: Gossypium; Gossypol; Hydroxymethylglutaryl CoA Reductases; Sesquiterpenes; Phytoalexins
PubMed: 26803304
DOI: 10.1007/s11427-016-5003-z -
Molecules (Basel, Switzerland) Sep 2021Parthenin, a sesquiterpene lactone of pseudoguaianolide type, is the representative secondary metabolite of the tropical weed (Asteraceae). It accounts for a multitude... (Review)
Review
Parthenin, a sesquiterpene lactone of pseudoguaianolide type, is the representative secondary metabolite of the tropical weed (Asteraceae). It accounts for a multitude of biological activities, including toxicity, allergenicity, allelopathy, and pharmacological aspects of the plant. Thus far, parthenin and its derivatives have been tested for chemotherapeutic abilities, medicinal properties, and herbicidal/pesticidal activities. However, due to the lack of toxicity-bioactivity relationship studies, the versatile properties of parthenin are relatively less utilised. The possibility of exploiting parthenin in different scientific fields (e.g., chemistry, medicine, and agriculture) makes it a subject of analytical discussion. The present review highlights the multifaceted uses of parthenin, on-going research, constraints in the practical applicability, and the possible workarounds for its successful utilisation. The main aim of this comprehensive discussion is to bring parthenin to the attention of researchers, pharmacologists, natural product chemists, and chemical biologists and to open the door for its multidimensional applications.
Topics: Asteraceae; Sesquiterpenes
PubMed: 34500778
DOI: 10.3390/molecules26175347 -
The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation.Molecules (Basel, Switzerland) Apr 2022Sesquiterpenes (SQs) are volatile compounds made by plants, insects, and marine organisms. SQ have a large range of biological properties and are potent inhibitors and... (Review)
Review
Sesquiterpenes (SQs) are volatile compounds made by plants, insects, and marine organisms. SQ have a large range of biological properties and are potent inhibitors and modulators of inflammation, targeting specific components of the nuclear factor-kappaB (NF-κB) signaling pathway and nitric oxide (NO) generation. Because SQs can be isolated from over 1600 genera and 2500 species grown worldwide, they are an attractive source of phytochemical therapeutics. The chemical structure and biosynthesis of SQs is complex, and the SQ scaffold represents extraordinary structural variety consisting of both acyclic and cyclic (mono, bi, tri, and tetracyclic) compounds. These structures can be decorated with a diverse range of functional groups and substituents, generating many stereospecific configurations. In this review, the effect of SQs on inflammation will be discussed in the context of their complex chemistry. Because inflammation is a multifactorial process, we focus on specific aspects of inflammation: the inhibition of NF-kB signaling, disruption of NO production and modulation of dendritic cells, mast cells, and monocytes. Although the molecular targets of SQs are varied, we discuss how these pathways may mediate the effects of SQs on inflammation.
Topics: Humans; Inflammation; Lipopolysaccharides; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Sesquiterpenes
PubMed: 35458648
DOI: 10.3390/molecules27082450 -
Molecules (Basel, Switzerland) Mar 2022Cancer is a leading cause of morbidity and mortality worldwide. The development of cancer involves aberrations in multiple pathways, representing promising targets for... (Review)
Review
Cancer is a leading cause of morbidity and mortality worldwide. The development of cancer involves aberrations in multiple pathways, representing promising targets for anti-cancer drug discovery. Natural products are regarded as a rich source for developing anti-cancer therapies due to their unique structures and favorable pharmacology and toxicology profiles. Deoxyelephantopin and isodeoxyelephantopin, sesquiterpene lactone compounds, are major components of and , which have long been used as traditional medicines to treat multiple ailments, including liver diseases, diabetes, bronchitis, fever, diarrhea, dysentery, cancer, renal disorders, and inflammation-associated diseases. Recently, deoxyelephantopin and isodeoxyelephantopin have been extensively explored for their anti-cancer activities. This review summarizes and discusses the anti-cancer activities of deoxyelephantopin and isodeoxyelephantopin, with an emphasis on their modes of action and molecular targets. Both compounds disrupt several processes involved in cancer progression by targeting multiple signaling pathways deregulated in cancers, including cell cycle and proliferation, cell survival, autophagy, and invasion pathways. Future directions of research on these two compounds towards anti-cancer drug development are discussed.
Topics: Antineoplastic Agents; Apoptosis; Asteraceae; Biological Products; Humans; Lactones; Neoplasms; Sesquiterpenes
PubMed: 35408483
DOI: 10.3390/molecules27072086 -
Biomedicine & Pharmacotherapy =... May 2020Costunolide (COS) and dehydrocostus lactone (DEH) are two natural sesquiterpene lactones with potential antitcancer activity against a range of cancer cell types both in... (Review)
Review
Costunolide (COS) and dehydrocostus lactone (DEH) are two natural sesquiterpene lactones with potential antitcancer activity against a range of cancer cell types both in vitro and in vivo, particularly for breast cancer and leukemia. There are many researches that have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of COS and DEH. However, while there is a great deal of evidence detailing the effects of COS and DEH on considerable signaling pathways and cellular functions, a global view of their mechanism of action remains elusive. This review systematically summarizes the antitumor activity and mechanism of COS and DEH in the recent reports, and discusses the effect of the key active part (α-methylene-γ-butyrolactone) of COS and DEH against cancer. Moreover, we also discuss the antineoplastic activity of COS and DEH derivatives to improve the cytotoxicity and safety index. We believe this review can provide a systemic reference to develop COS and DEH as anticancer agents.
Topics: Antineoplastic Agents, Phytogenic; Asteraceae; Cell Line, Tumor; Humans; Lactones; Sesquiterpenes
PubMed: 32014691
DOI: 10.1016/j.biopha.2020.109955 -
International Journal of Molecular... Jun 2013Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as... (Review)
Review
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.
Topics: Crops, Agricultural; Humans; Lactones; Nutritional Physiological Phenomena; Plants; Sesquiterpenes; Taste
PubMed: 23783276
DOI: 10.3390/ijms140612780 -
Chemistry (Weinheim An Der Bergstrasse,... May 2022The known sesquiterpenes that arise biosynthetically from hedycaryol are summarised. Reasonings for the assignments of their absolute configurations are discussed. The... (Review)
Review
The known sesquiterpenes that arise biosynthetically from hedycaryol are summarised. Reasonings for the assignments of their absolute configurations are discussed. The analysis provided here suggests that reprotonations at the C1=C10 double bond of hedycaryol are directed toward C1 and generally lead to 6-6 bicyclic compounds, while reprotonations at the C4=C5 double bond occur at C4 and result in 5-7 bicyclic compounds. Read more in the Review by H. Xu and J. S. Dickschat (DOI: 10.1002/chem.202200405).
Topics: Sesquiterpenes
PubMed: 35239190
DOI: 10.1002/chem.202200405 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2020This review summarises known sesquiterpenes whose biosyntheses proceed through the intermediate germacrene A. First, the occurrence and biosynthesis of germacrene A in... (Review)
Review
This review summarises known sesquiterpenes whose biosyntheses proceed through the intermediate germacrene A. First, the occurrence and biosynthesis of germacrene A in Nature and its peculiar chemistry will be highlighted, followed by a discussion of 6-6 and 5-7 bicyclic compounds and their more complex derivatives. For each compound the absolute configuration, if it is known, and the reasoning for its assignment is presented.
Topics: Sesquiterpenes; Sesquiterpenes, Germacrane
PubMed: 32442350
DOI: 10.1002/chem.202002163