Putative Mode of Action of the Monoterpenoids Linalool, Methyl Eugenol, Estragole, and Citronellal on Ligand-Gated Ion Channels

Essential oil has been used as sedatives,anticonvulsants,and local anesthetics in traditional medical remedies;as preservatives for food,fruit,vegetable,and grain storage;and as bio-pesticides for food production.Linalool(LL),along with a few other major components such as methyl eugenol(ME),estragole(EG),and citronellal,are the active chemicals in many essential oils such as basil oil.Basil oil and the aforementioned monoterpenoids are potent against insect pests.However,the molecular mechanism of action of these chemical constituents is not well understood.It is well-known that the c-aminobutyric acid type A receptors(GABAARs)and nicotinic acetylcholine receptor(nAChR)are primary molecular targets of the synthetic insecticides used in the market today.Furthermore,the GABAAR-targeted therapeutics have been used in clinics for many decades,including barbiturates and benzodiazepines,to name just a few.In this research,we studied the electrophysiological effects of LL,ME,EG,and citronellal on GABAAR and nAChR to further understand their versatility as therapeutic agents in traditional remedies and as insecticides.Our results revealed that LL inhibits both GABAAR and nAChR,which may explain its insecticidal activity.LL is a concentration-dependent,noncompetitive inhibitor on GABAAR,as the half-maximal effective concentration(EC50)values of c-aminobutyric acid(GABA)for the rat a1b3c2L GABAAR were not affected by LL:(36.2±7.9)lmol-1 and(36.1±23.8)μmol·L-1 in the absence and presence of 5 mmol·L-1 LL,respectively.The half-maximal inhibitory concentration(IC50)of LL on GABAAR was approximately 3.2 mmol·L-1.Considering that multiple monoterpenoids are found within the same essential oil,it is likely that LL has a synergistic effect with ME,which has been previously characterized as both a GABAAR agonist and a positive allosteric modulator,and with other monoterpenoids,which offers a possible explanation for the sedative and anticonvulsant effects and the insecticidal activities of LL.

室内空气中单萜类化合物检测方法的研究

Monoterpenoids are widely existing in indoor air.A GC-MS method was established for determination of monoterpenoids in the indoor air by using silonite coated canisters(SUMMA canisters),and preconcentrating low level samples utilizing three stages focuser.The method was suitable for the determination of trace VOCs in indoors air.The detection limits of method for α-pinene and β-pinene were both 0.71 μg/m3.

Acaricidal activities of some essential oils and their monoterpenoidal constituents against house dust mite,Dermatophagoides pteronyssinus (Acari:Pyroglyphidae)

The acaricidal activities of fourteen essential oils and fourteen of their major monoterpenoids were tested against house dust mites Dermatophagoides pteronyssinus. Five concentrations were used over two different time intervals 24 and 48 h under laboratory conditions. In general, it was noticed that the acaricidal effect based on LC50 of either essential oils or monoterpenoids against the mite was time dependant. The LCso values were decreased by increasing of exposure time. Clove, matrecary, chenopodium, rosemary, eucalyptus and caraway oils were shown to have high activity. As for the monoterpenoids, cinnamaldehyde and chlorothymol were found to be the most effective followed by citronellol. This study suggests the use of the essential oils and their major constituents as ecofriendly biodegradable agents for the control of house dust mite, D. pteronyssinus.

Ethnobotany, Pharmacology and Phytochemical Investigations of the Seeds of <i>Pentaclethra macrophylla</i>Benth (Mimosaceae)

Phytochemical investigation of the seeds of Pentaclethra macrophylla led to the isolation of a mixture of two new aromatic monoterpene glycosides, pentamacrophylloside A (1a) and pentamacrophylloside B (1b), together with six known secondary metabolites: Comososide (2), secopentaclethroside (3), caffeoylputrescine (4), β-sitosterol-3-O-β-D-glucopyranoside (5), 2-hydroxymethyl-5-(2-hydroxypropan-2-yl)phenol (6), and sucrose (7). Their structures were elucidated mainly by extensive spectroscopic analysis (1D and 2D NMR), high-resolution mass spectrometry and by comparison of their spectral data with those of related compounds. The extracts and compounds 3 and 4 were screened for their antimicrobial activity. The n-BuOH fraction showed a weak effect against three microbial strains: Candida albicans (MIC: 256 μg/mL), Enterococcus faecalis (MIC: 512 μg/mL), and Proteus mirabilis (MIC: 512 μg/mL) while no significant inhibition was observed for pure compounds when compared to ketoconazole and ciprofloxacin used as references. Furthermore, the ethnobotany and pharmacology of this plant are reviewed, and the chemophenetic significance of the isolation of the above secondary metabolites is discussed. This is the first report on the isolation of aromatic monoterpenoids from a plant of the genus Pentaclethra.

Evaluation of antimycobacterium activity of the essential oils of cumin (<i>Cuminum cyminum</i>), clove (Eugenia caryophyllata), cinnamon (<i>Cinnamomum verum</i>), laurel (<i>Laurus nobilis</i>) and anis (<i>Pimpinella anisum</i>) against <i>Mycobacterium tuberculosis</i>

In this study Essential oils were used with cumin, cloves, cinnamon, laurel and anis to determine Minimum Inhibitory Concentration (MIC) against Mycobacterium tuberculosis strains. The MICs were determined on M. tuberculosis H37Rv sensitive to all five firstline antituberculosis drugs (streptomycin, isoniazid, rifampicin, ethambutol and pirazinamide), two H37-Rv (CH-8 and CH-15) isoniazid-resistant, two H37Rv (CH-07 and CH-09) rifampicin-resistant, two H37Rv (CH-03 and CH-06) streptomycin-resistant, and two H37Rv (CH-09 and CH-10) ethambutol-resistant using the microplate alamar blue assay. The results obtained showed that the cumin and cinnamon essential oils showed a MIC of 12.5 μg/ml against reference strain H37Rv. The five essential oils used in this study were effective against the isoniazid-resistant variant of H37RV with MIC values in the range 12.5-100 μg/ml, the most potent being the cumin and cin-namon (MIC = 12.5). Similar results were obtained against rifampicin-resistant variant of H37RV with MIC values in the range 12.5-100 μg/ml;the most active ones?in this case were the essential oils of cumin and cloves. The essential oils of anis and laurel were active with MIC value to 100 μg/ml. Clove, cumin, and cinnamon essential oils were active against all strains utilized in this study, with MIC values in the range 6.25 μg/ml to 25 μg/ml.

A new monoterpenoid indole alkaloid from Rauvolfia yunnanensis

One new monoterpenoid indole alkaloid, l l-methoxyburnamine-17-O-3′,4′,5′-trimethoxybenzoate （1）, was isolated from Rauvolfia yunnanensis Tsiang. Its structure was identified by speclroscopic evidences.

Monoterpenoid indole alkaloids from Alstonia rostrata

Four new monoterpenoid indole alkaloids,alstrostines C-F together with thirteen known alkaloids were isolated from the leaves and twigs of Alstonia rostrata.All structures of new compounds were elucidated based on NMR,FTIR,UV,and MS spectroscopic data.Alstrostines C-E might originate from keto-enol tautomerism of preakummicine during biogenetic pathway of akummicine.

The chemical constituents from Schisandra propinqua var. intermedia

A new cinnamic acid monoterpenoid ester, intermedin C （1）, was isolated from the aerial parts of Schisandra propinqua var. interthedia. The structure of 1 was elucidated by spectroscopic methods including extensive ^1D and 2D NMR techniques.

Bousmekines A-E,New Alkaloids from Two Bousigonia Species:B.angustifolia and B.mekongensis

Four new monoterpenoid indole alkaloids,bousmekines A-D(1-4),and one new pyranopyridine alkaloid,bousmekine E(5),were isolated from the twigs and leaves of Bousigonia angustifolia and Bousigonia mekongensis.Their structures including absolute configurations were elucidated by a combination of MS,NMR,ECD calculation,and single-crystal X-ray diffraction analysis.Compound 2 was an eburnea-type MIAs characterized by a rare chlorine atom while 5 possessed a novel pyranopyridine moiety.Their cytotoxicities against several human cancer cell lines were evaluated and compound 1 exhibited significant cytotoxicity with IC50 values of 0.8-7.4μM.

Hybrid Monoterpenoid Indole Alkaloids Obtained as Artifacts from Rauvolfia tetraphylla

Five new hybrid monoterpenoid indole alkaloids bearing an unusual 2,2-dimethyl-4-oxopiperidin-6-yl moiety,namely rauvotetraphyllines F–H(1,3,4),17-epi-rauvotetraphylline F(2)and 21-epi-rauvotetraphylline H(5),were isolated from the aerial parts of Rauvolfia tetraphylla.Their structures were established by extensive spectroscopic analysis.The new alkaloids were evaluated for their cytotoxicity in vitro against five human cancer cell lines.

A chromosome-level genome assembly reveals that a bipartite gene cluster formed via an inverted duplication controls monoterpenoid biosynthesis in Schizonepeta tenuifolia

Biosynthetic gene clusters(BGCs)are regions of a genome where genes involved in a biosynthetic pathway are in proximity.The origin and evolution of plant BGCs as well as their role in specialized metabolism remain largely unclear.In this study,we have assembled a chromosome-scale genome of Japanese catnip(Schizonepeta tenuifolia)and discovered a BGC that contains multiple copies of genes involved in four adjacent steps in the biosynthesis of p-menthane monoterpenoids.This BGC has an unprecedented bipartite structure,with mirrored biosynthetic regions separated by 260 kilobases.This bipartite BGC includes identical copies of a gene encoding an old yellow enzyme,a type of flavin-dependent reductase.In vitro assays and virus-induced gene silencing revealed that this gene encodes the missing isopiperitenone reductase.This enzyme evolved from a completely different enzyme family to isopiperitenone reductase from closely related Mentha spp.,indicating convergent evolution of this pathway step.Phylogenomic analysis revealed that this bipartite BGC has emerged uniquely in the S.tenuifolia lineage and through insertion of pathway genes into a region rich in monoterpene synthases.The cluster gained its bipartite structure via an inverted duplication.The discovered bipartite BGC for p-menthane biosynthesis in S.tenuifolia has similarities to the recently described duplicated p-menthane biosynthesis gene pairs in the Mentha longifolia genome,providing an example of the convergent evolution of gene order.This work expands our understanding of plant BGCs with respect to both form and evolution,and highlights the power of BGCs for gene discovery in plant biosynthetic pathways.

Chemical Constituents in Essential Oils from Elsholtzia ciliata and Their Antimicrobial Activities

Objective To compare the chemical constituents in the essential oils from the leaves, flowers, and seeds of Elsholtzia ciliata and their antimicrobial activities. Methods The chemical constituents in essential oils were extracted by the hydro-distillation method and analyzed by GC-MS. The chemical constituents in essential oils were identified on the basis of comparison on their retention indices and MS spectrum with published data. Moreover, the antimicrobial activities of the chemical constituents in the oils against the growth of six bacteria strains and one pathogenic yeast strain were evaluated by using minimum inhibitory concentration and minimum bactericidal concentration methods. Results A total of 58 compounds were identified, while compounds 31, 35, and 36 were identified in the essential oils from the leaves, flowers, and seeds, respectively. Fifteen compounds were identified as shared constituents in the leaves, flowers, and seeds. The chemical constituents in the essential oils showed the inhibitory activities against the six bacteria strains and the yeast strain. Conclusion The major constituents are different in the essential oils of the leaves, flowers, and seeds. The major chemical constituents in the essential oils are monoterpenoids and sesquiterpenoids. And the chemical constituents in the essential oils obtained from the leaves show higher inhibitory activities especially against Bacillus subtillis CMCC63501 and Escherichia coli ATCC25922.

Chromosome-level assembly and analysis of the Thymus genome provide insights into glandular secretory trichome formation and monoterpenoid biosynthesis in thyme

Thyme has medicinal and aromatic value because of its potent antimicrobial and antioxidant properties.However,the absence of a fully sequenced thyme genome limits functional genomic studies of Chinese native thymes.Thymus quinquecostatus Celak.,which contains large amounts of bioactive monoterpenes suchas thymol and carvacrol,is an important wild medicinal and aromatic plant in China.Monoterpenoids are abundant in glandular secretory trichomes.Here,high-fidelity and chromatin conformation capture technologies were used to assemble and annotate the T.quinquecostatus genome at the chromosome level.The 13 chromosomes of T.quinquecostatus had a total length of 528.66 Mb,a contig N50 of 8.06 Mb,and a BUSCO score of 97.34%.We found that T.quinquecostatus had experienced two whole-genome duplications,with the most recent event occurring4.34 million years ago.Deep analyses of the genome,in conjunction with comparative genomic,phylogenetic,transcriptomic,and metabonomic studies,uncovered many regulatory factors and genes related to monoterpenoids and glandular secretory trichome development.Genes encoding terpene synthase(TPS),cytochrome P450 monooxygenases(CYPs),short-chain dehydrogenase/reductase(SDR),R2R3-MYB,and homeodomain-leucine zipper(HD-ZIP)IV were among those present in the T.quinquecostatus genome.Notably,Tq02G002290.1(TqTPS1)was shown to encode the terpene synthase responsible for catalyzing production of the main monoterpene product g-terpinene from geranyl diphosphate(GPP).Our study provides significant insight into the mechanisms of glandular secretory trichome formation and monoterpenoid biosynthesis in thyme.This work will facilitate the development of molecular breeding tools to enhance the production of bioactive secondary metabolites in Lamiaceae.

Stable carbon isotope composition of monoterpanes in essential oils and crude oils

Twenty-five monoterpanes from six types of essential oils and hydrogenated turpentine oil have been identified and their stable carbon isotope composition determined.Monoterpanes in essential oils sourced from terrestrial higher plants display a δ13C value in the range of-34‰-26‰,and mostly between-29‰ and-27‰.The δ13C value of any single monoterpane is very consistent in different essential oils.Acyclic monoterpanes show closer isotope composition between-28.6‰ and-26.2‰,with an average value of-27.7‰.In contrast,the isotope composition of cyclic monoterpanes is more scattered with an average value of-28.6‰.Isotopic fractionation with 13C enrichment has been observed during both artificial and geological hydrogenation of monoterpenoids to monoterpanes,and this is more obvious for the acyclic monoterpenoids.In addition to higher plants,acyclic monoterpane 2,6-dimethylheptane in crude oil can also be originated from other organic inputs.

Discovery of Natural Co-occurring Enantiomers of Monoterpenoid Indole Alkaloids

Main observation and conclusion Two new pairs of monoterpenoid indole alkaloids(MIAs)enantiomers as well as their new congeners were isolated from stems of Tabernaemontana bovina Lour.(Apocynaceae).Their structures were elucidated by spectroscopic analyses and confirmed by X-ray diffractions and computational calculations.Tabovine A,tabovine B and tabovines C-D possessed unprecedented 6/5/5/6/6,6/5/5/6/5 and 6/5/6/6/6 ring systems,respectively.It is the first time to report co-occurring enantiomers of MIAs.Additionally,the explanation concerning biogenesis of MIAs was provided.The findings would open a new window where we could disclose more diverse MIAs.

Chemical constituents from Teucrium viscidum

A new monoterpenoid,4,5,8-trihydroxy-6（7）-en-decenoic acid γ-lactone（1） and six known compounds,3,7-dimethyloct-1-ene-3,6,7-triol（2）,2,8-bornanediol（3）,1-（4-hydroxyphenyl）ethane-1,2-diol（4）,2-（3-methoxy-4-hydroxyphenyl）-propane-1,3-diol（5）,indole-3-carboxylic acid（6）,and 3-hydroxy-benzenemethanol（7） were isolated from the whole parts of Teucrium viscidum.Their structures were established by a combination of spectroscopic data analysis,besides comparison with literature data.Compounds 2–7 described above were isolated from this genus for the first time.

Monoterpenoid Indole Alkaloids with Promoting Neurite Growth from Tabernaemontana divaricata

Phytochemical investigations on Tabernaemontana divaricata led to the isolation of seven undescribed monoterpenoid indole alkaloids,taberdicatines A-G(1-7).Taberdicatines A-C might be derived from Aspidosperma-type alkaloid,less skeletal carbons in 1-2 and an additional carbon in 3.Taberdicatines D-E(4-5)were attributed to Iboga alkaloids with enantiomeric skeleton,respectively.Alkaloid 3 could promote the neurite growth of mouse primary cortical neurons at the concentration of 5 pimol/L.

Progress in NMR-based metabolomics of Catharanthus roseus

Metabolomics has been rapidly developed as an important field in plant sciences and natural products chemistry.As the only natural source for a diversity of monoterpenoid indole alkaloids(MIAs),especially the low-abundance antitumor agents vinblastine and vincristine,Catharanthus roseus is highly valued and has been studied extensively as a model for medicinal plants improvement.Due to multistep enzymatic biosynthesis and complex regulation,genetic modification in the MIA pathway has resulted in complicated changes of both secondary and primary metabolism in C.roseus,affecting not only the MIA pathway but also other pathways.Research at the metabolic level is necessary to increase knowledge on the genetic regulation of the whole metabolic network connected to MIA biosynthesis.Nuclear magnetic resonance(NMR)is a very suitable and powerful complementary technique for the identification and quantification of metabolites in the plant matrix.NMR-based metabolomics has been used in studies of C.roseus for pathway elucidation,understanding stress responses,classification among different cultivars,safety and quality controls of transgenic plants,cross talk between pathways,and diversion of carbon fluxes,with the aim of fully unravelling MIA biosynthesis,its regulation and the function of the alkaloids in the plant from a systems biology point of view.