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The Journal of Experimental Biology Jan 2021Monoterpenes are molecules with insecticide properties whose mechanism of action is, however, not completely elucidated. Furthermore, they seem to be able to modulate...
Monoterpenes are molecules with insecticide properties whose mechanism of action is, however, not completely elucidated. Furthermore, they seem to be able to modulate the monoaminergic system and several behavioural aspects in insects. In particular, tyramine (TA) and octopamine (OA) and their associated receptors orchestrate physiological processes such as feeding, locomotion and metabolism. Here, we show that monoterpenes not only act as biopesticides in species but also can cause complex behavioural alterations that require functional type 1 tyramine receptors (TAR1s). Variations in metabolic traits as well as locomotory activity were evaluated in both and after treatment with three monoterpenes. A TAR1-defective strain () was used to better understand the relationships between the receptor and monoterpene-related behavioural changes. Immunohistochemistry analysis revealed that, in the brain, TAR1 appeared to be mainly expressed in the pars intercerebralis, lateral horn, olfactory and optic lobes and suboesophageal ganglion lobes. In comparison to wild-type , the flies showed a phenotype characterized by higher triglyceride levels and food intake as well as lower locomotory activity. The monoterpenes, tested at sublethal concentrations, were able to induce a downregulation of the coding gene in both species. Furthermore, monoterpenes also altered the behaviour in wild-type and 24 h after continuous monoterpene exposure. Interestingly, they were ineffective in modifying the physiological performance of TAR1-defective flies. In conclusion, it appears that monoterpenes not only act as biopesticides for but also can interfere with behaviour and metabolism in a TAR1-dependent fashion.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Monoterpenes; Octopamine; Tyramine
PubMed: 33234680
DOI: 10.1242/jeb.232116 -
Archives of Biochemistry and Biophysics Nov 2022Rhodococcus globerulus (R. globerulus) isolated from soil beneath Eucalyptus sp. was found to live on the monoterpenes 1,8-cineole, p-cymene and (R)- and (S)-limonene as...
Rhodococcus globerulus (R. globerulus) isolated from soil beneath Eucalyptus sp. was found to live on the monoterpenes 1,8-cineole, p-cymene and (R)- and (S)-limonene as sole sources of carbon and energy. Previous metabolic studies revealed that R. globerulus is capable of living on 1,8-cineole, the main monoterpene component of eucalyptus essential oil through the activity of cytochrome P450 (CYP176A1) [1]. Genomic sequencing of R. globerulus revealed a novel putative cytochrome P450 (CYP108N12) that shares 48% sequence identity with CYP108A1 (P450) from Pseudomonas sp., an α-terpineol hydroxylase. Given the sequence similarity between CYP108N12 and P450, it was hypothesised that CYP108N12 may be responsible for initiating the biodegradation of a monoterpene structurally similar to α-terpineol such as (R)-limonene, (S)-limonene or p-cymene. Encoded within the operon containing CYP108N12 were two putative bacterial P450 redox partners and putative alcohol and aldehyde dehydrogenases, suggesting a complete catalytic system for activating these monoterpenes. Binding studies revealed that p-cymene and (R)- and (S)-limonene all bound tightly to CYP108N12 but α-terpineol did not. A catalytically active system was reconstituted using the non-native redox partner putidaredoxin and putidaredoxin reductase that act with CYP101A1 (P450) from Pseudomonas. This reconstituted system catalysed the hydroxylation of p-cymene to 4-isopropylbenzyl alcohol, and (R)- and (S)-limonene to (R)- and (S)-perillyl alcohol, respectively. R. globerulus was successfully grown on solely p-cymene, (R)-limonene or (S)-limonene. CYP108N12 was detected when R. globerulus was grown on p-cymene, but not either limonene enantiomer. The native function of CYP108N12 is therefore proposed to be initiation of p-cymene biodegradation by methyl oxidation and is a potentially attractive biocatalyst capable of specific benzylic and allylic hydroxylation.
Topics: Limonene; Eucalyptol; Monoterpenes; Cytochrome P-450 Enzyme System; Pseudomonas; Carbon; Soil; Oils, Volatile; Aldehydes; Terpenes
PubMed: 36155781
DOI: 10.1016/j.abb.2022.109410 -
Phytochemistry Apr 2022Natural products from plants have gained prominence in the search for therapeutic alternatives. Monoterpenes, such as carvone, are suggested as candidates for the... (Review)
Review
Natural products from plants have gained prominence in the search for therapeutic alternatives. Monoterpenes, such as carvone, are suggested as candidates for the treatment of several diseases. Therefore, the objective of this study is to review the pharmacological activities of carvone in experimental models in vitro and in vivo. For this, the searches were carried out in May 2020 (upgraded in July 2021) in the databases of PubMed, Web of Science and Scopus and gathered studies on the pharmacological activities of carvone. Two independent reviewers performed the selection of articles using the Rayyan application, extracted the relevant data and assessed the methodological quality of the selected studies using Syrcle's risk of bias tool. Ninety-one articles were selected that described 10 pharmacological activities of carvone, such as antimicrobial, antispasmodic, anti-inflammatory, antioxidant, antinociceptive, anticonvulsant, among others. The evaluation of the methodological quality presented an uncertain risk of bias for most studies. In light of that, carvone stands out as a viable and promising alternative in the treatment of several pathological conditions. However, carrying out studies to evaluate possible mechanisms of action and the safety of this monoterpene is recommended.
Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Cyclohexane Monoterpenes; Monoterpenes
PubMed: 34999510
DOI: 10.1016/j.phytochem.2021.113080 -
International Journal of Molecular... Apr 2021Terpenes-a diverse group of secondary metabolites-constitute the largest class of natural products abundant in almost every plant species. The properties of concrete... (Review)
Review
Terpenes-a diverse group of secondary metabolites-constitute the largest class of natural products abundant in almost every plant species. The properties of concrete terpenes and essential oils have been intensively studied due to their widespread use in the pharmaceutical, food and cosmetics industries. Despite the popularity of these aromatic compounds, their derivatives, terpenoids, are still not comprehensively characterized despite exhibiting potent bioactive properties. This review aims to assess the anticancer properties of selected monoterpenes including carvone, carvacrol, perillyl alcohol, perillaldehyde, limonene, menthol and their derivatives while also evaluating potential applications as novel anticancer treatments. Special attention is paid to functional groups that improve the bioactivity of monoterpene molecules. This review also covers the therapeutic potential of deep eutectic solvents that contain monoterpene substances. Taken together, the literature supports the use of monoterpene derivatives in the development of new alternatives for disease treatment and prevention.
Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Discovery; Humans; Monoterpenes; Neoplasms; Plants
PubMed: 33946245
DOI: 10.3390/ijms22094763 -
Molecules (Basel, Switzerland) Feb 2022Two undescribed ether derivatives of sesquiterpenes, 1-ethoxycaryolane-1, 9-diol () and 2-ethoxyclovane-2, 9-diol (), and one new monoterpene glycoside,...
Two undescribed ether derivatives of sesquiterpenes, 1-ethoxycaryolane-1, 9-diol () and 2-ethoxyclovane-2, 9-diol (), and one new monoterpene glycoside, p-menthane-1,2,8-triol-4-O--D-glucoside (), were obtained, together with eight known compounds from the stems and leaves of . Their structures were elucidated by spectroscopic methods. Compounds - were evaluated for their potency against and clinical methicillin-resistant (MRSA). Among them, compound was weakly active against (MIC = 128 μg/mL), and compounds and exhibited good antibacterial activity against and MRSA (MICs = 2-8 µg/mL). A primary mechanism study revealed that compounds and could kill bacteria by destroying bacterial cell membranes. Moreover, compounds and were not susceptible to drug resistance development.
Topics: Anti-Bacterial Agents; Humans; Illicium; Methicillin-Resistant Staphylococcus aureus; Monoterpenes; Plant Leaves; Plant Stems; Sesquiterpenes; Staphylococcal Infections
PubMed: 35164380
DOI: 10.3390/molecules27031115 -
Mini Reviews in Medicinal Chemistry 2021Limonene and perillyl alcohol are natural monoterpenes that have attracted the attention of medicinal chemists due to their promising anticancer activities. Considering... (Review)
Review
Limonene and perillyl alcohol are natural monoterpenes that have attracted the attention of medicinal chemists due to their promising anticancer activities. Considering this, both compounds were explored as scaffolds to obtain various derivatives with anticancer activity. In this review, the data are organized for the first time, with a focus on the synthetic methods and strategies to obtain the derivatives throughout the period from 2000 to 2020. A brief discussion regarding the structure and activity relationships of the most active derivatives, stereoisomers, and their mechanisms of action is presented. Among the active compounds, a series of limonenes with thiosemicarbazone groups and perillyl alcohol hybrids with glycosides or drugs are illustrated. Taking all of this into account, this review may help researchers develop new promising anticancer candidates based on the structures of limonene and perillyl alcohol.
Topics: Antineoplastic Agents; Carbohydrates; Cell Survival; Humans; Limonene; Monoterpenes; Neoplasms; Structure-Activity Relationship; Thiosemicarbazones
PubMed: 33583370
DOI: 10.2174/1389557521666210212150504 -
Molecular Biology Reports Jul 2021Secondary metabolites have been recognized for centuries as medicinal agents, in particular monoterpenes which have been the target of research in the discovery of...
Secondary metabolites have been recognized for centuries as medicinal agents, in particular monoterpenes which have been the target of research in the discovery of antineoplastic drugs, as they have potential antitumor effect and low toxicity and are used as additives in foods and cosmetics. Another advantage of monoterpenes is structural diversity, which gives greater plasticity when interacting with cells. The purpose of this review was to summarize and critically discuss the anticancer potential of monoterpenes and their respective mechanisms of action. A systematic review of articles in the MEDLINE/PubMed, Web of Science, Scopus and Science Direct electronic databases was independently conducted by three reviewers using the combination of the following keywords: monoterpenes AND anticancer AND in vitro. Restriction in selecting articles followed pre-established inclusion and exclusion criteria by the reviewers, and also a time limitation with works published between 2015 and 2019 being selected. In total, 39 works were deemed eligible for inclusion in the final review. Monoterpenes have cytotoxic activity in a wide variety of tumor cell lines, and mainly appear to exert this effect by inducing apoptosis caused by oxidative stress. In addition, improved use of monoterpenes when used in drug delivery systems and the synergistic effect with conventional chemotherapeutic drugs are reported. These findings validate this class of compounds as a promising source of chemotherapeutic drugs yet to be explored.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Monoterpenes; Neoplasms; Oxidative Stress
PubMed: 34304392
DOI: 10.1007/s11033-021-06578-5 -
Biomedicine & Pharmacotherapy =... May 2022Paeoniflorin is a water-soluble monoterpenoid glycoside that can be derived from multiple herbaceous plants, such as Radix Paeoniae Rubra, Radix Paeoniae Alba, Paeonia... (Review)
Review
Paeoniflorin is a water-soluble monoterpenoid glycoside that can be derived from multiple herbaceous plants, such as Radix Paeoniae Rubra, Radix Paeoniae Alba, Paeonia suffruticosa and Cimicifugae Foetidae. Multiple studies have suggested that Paeoniflorin possesses an excellent anti-tumor effect in variety of tumors, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer and bladder cancer. It can induce cell apoptosis, inhibit proliferation, invasion and metastasis via different molecular mechanisms, which are mainly involved in nuclear transcription factor kappα (NF-κB), B-cell lymphoma-2(Bcl-2) family, MicroRNA, neural precursor cell expressed developmentally down-regulated protein 4(NEDD4) signaling pathway, transcription activating factor (STAT3), p21, p53/14-3-3 signaling pathway, transforming growth factor-β1(TGF-β1)/Smads signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway and Notch-1. Current studies on anti-tumor effect and mechanism of action of Paeoniflorin remain unclear. Therefore, this study reviews the research progress in the anti-tumor effect and mechanism of Paeoniflorin in an attempt to provide a new thought and theoretical basis for further development and clinical application of Paeoniflorin.
Topics: Glucosides; Humans; Monoterpenes; Neoplasms; Paeonia
PubMed: 35279012
DOI: 10.1016/j.biopha.2022.112800 -
Molecules (Basel, Switzerland) Jun 2020Epicatechocorynantheines A and B, and epicatechocorynantheidine were isolated from the stem bark of . These molecules were pinpointed, and their isolation streamlined,...
Epicatechocorynantheines A and B, and epicatechocorynantheidine were isolated from the stem bark of . These molecules were pinpointed, and their isolation streamlined, by a molecular networking strategy. The structural elucidation was unambiguously accomplished from HRMS and 1D/2D NMR data. These compounds represent the first examples of corynanthean-type alkaloids tethered with a flavonoid. Epicatechocorynantheidine notably instigated two connections between the monoterpene indole alkaloid and the flavonoid, yielding an unprecedented octacyclic appendage. These flavoalkaloids exerted moderate antiplasmodial activities.
Topics: Anthelmintics; Catechin; Flavonoids; Indole Alkaloids; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Monoterpenes; Pausinystalia; Plant Bark; Plant Stems
PubMed: 32517373
DOI: 10.3390/molecules25112654 -
Journal of Food Biochemistry Dec 2021Globally, cancer is one of the deadliest diseases, estimated to cause 9.9 million deaths in 2020. Conventional cancer treatments commonly involve mono-chemotherapy or a... (Review)
Review
Globally, cancer is one of the deadliest diseases, estimated to cause 9.9 million deaths in 2020. Conventional cancer treatments commonly involve mono-chemotherapy or a combination of radiotherapy and mono-chemotherapy. However, the negative side effects of these approaches have been extensively reported and have prompted the search for new therapeutic drugs. Over the past few years, numerous dietary agents, medicinal plants, and their phytochemicals gained considerable therapeutic importance because of their anticancer, antiviral, anti-inflammatory, and antioxidant activities. Recent years have shown that essential oils possess therapeutic effects against numerous cancers. They are primarily used due to their lesser side effects than standard chemotherapeutic drugs. Carvacrol (CRV) is a phenolic monoterpenoid found in essential oils of oregano, thyme, pepperwort, wild bergamot, and other plants. Numerous anticancer reports of CRV substantiated that the main mechanistic action of CRV involves reduction in the viability of cancer cells and induction of apoptosis via both intrinsic and extrinsic pathways. CRV also obstructs the migration and invasion of cells leading to the suppressed proliferation rate. Furthermore, CRV mediates augmented ROS generation resulting in DNA damage and also halts the progression of cell cycle. Treatment of CRV modulates the expression of apoptotic proteins (Bax, Bad) and molecular targets of various signaling pathways (PI3K/AKT/mTOR, MAPKs, and Notch) in multiple solid carcinomas. Hence, this review aimed to acquire and disseminate the knowledge of chemopreventive and anticancer effects of CRV and the mechanisms of action already described for the compound against numerous cancers, including solid carcinomas, to guide future research. PRACTICAL APPLICATIONS: Development and formulation of phytocompound based anticancer drug agents to counteract the aftereffects of chemotherapeutic drugs is a propitious approach. CRV is a monoterpenoid consisting of a phenolic group obtained from the essential oils of oregano and thyme. These plants are being used as food flavoring spice and as fragrance ingredient in various cosmetic formulations. For the use of CRV as an efficient chemopreventive agent, different therapeutic interactions of CRV along with its targeted pathways and molecules, involved in the regulation of onset and progression of various types of solid carcinomas, need to be studied and explored thoroughly.
Topics: Carcinoma; Cymenes; Humans; Monoterpenes; Phosphatidylinositol 3-Kinases
PubMed: 34796513
DOI: 10.1111/jfbc.14010