cis-Nerolidol

Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models.[Pubmed:32650602]

Nutrients. 2020 Jul 8;12(7). pii: nu12072032.

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-alpha-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 microM and 50 microM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1beta, IL-6, and TNF-alpha) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-alpha-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

Functional characterization of a new terpene synthase from Plectranthus amboinicus.[Pubmed:32614884]

PLoS One. 2020 Jul 2;15(7):e0235416.

Plectranthus amboinicus (Lour.) Spreng is an aromatic medicinal herb known for its therapeutic and nutritional properties attributed by the presence of monoterpene and sesquiterpene compounds. Up until now, research on terpenoid biosynthesis has focused on a few mint species with economic importance such as thyme and oregano, yet the terpene synthases responsible for monoterpene production in P. amboinicus have not been described. Here we report the isolation, heterologous expression and functional characterization of a terpene synthase involved in P. amboinicus terpenoid biosynthesis. A putative monoterpene synthase gene (PamTps1) from P. amboinicus was isolated with an open reading frame of 1797 bp encoding a predicted protein of 598 amino acids with molecular weight of 69.6 kDa. PamTps1 shares 60-70% amino acid sequence similarity with other known terpene synthases of Lamiaceae. The in vitro enzymatic activity of PamTps1 demonstrated the conversion of geranyl pyrophosphate and farnesyl pyrophosphate exclusively into linalool and nerolidol, respectively, and thus PamTps1 was classified as a linalool/nerolidol synthase. In vivo activity of PamTps1 in a recombinant Escherichia coli strain revealed production of linalool and nerolidol which correlated with its in vitro activity. This outcome validated the multi-substrate usage of this enzyme in producing linalool and nerolidol both in in vivo and in vitro systems. The transcript level of PamTps1 was prominent in the leaf during daytime as compared to the stem. Gas chromatography-mass spectrometry (GC-MS) and quantitative real-time PCR analyses showed that maximal linalool level was released during the daytime and lower at night following a diurnal circadian pattern which correlated with the PamTps1 expression pattern. The PamTps1 cloned herein provides a molecular basis for the terpenoid biosynthesis in this local herb that could be exploited for valuable production using metabolic engineering in both microbial and plant systems.

Chemical and Enantioselective Analysis of the Leaf Essential Oil from Piper coruscans Kunth (Piperaceae), a Costal and Amazonian Native Species of Ecuador.[Pubmed:32599869]

Plants (Basel). 2020 Jun 24;9(6). pii: plants9060791.

In the present study, an essential oil was distilled from the leaves of Piper coruscans Kunth, a native Amazonian species belonging to the family Piperaceae and quite common in Ecuador. The chemical analysis was performed by GC-MS (qualitative) and GC-FID (quantitative), on polar and non-polar columns, detecting a total of 58 compounds of which 52 were identified. All the identified compounds were quantified. The essential oil was mainly constituted of sesquiterpenes (54.1-55.0%) and oxygenated sesquiterpenoids (32.5-33.6%), the major constituents being: (E)-beta-caryophyllene (24.1-25.0%), alpha-humulene (11.6-12.0%), caryophyllene oxide (9.3-10.9%), linalool (4.5-5.2%), humulene epoxide II (3.6-4.1%), (E)-nerolidol (3.7-4.0%), alpha-copaene (3.7-3.9%), alpha-muurolol (3.4-3.7%), alpha-selinene (3.4-3.5%), beta-selinene (3.1-3.3%), and one undetermined oxygenated sesquiterpenoid (3.1-3.3%). The aqueous phase (hydrolate) of the distillation process was also submitted to chemical analysis, showing linalool as the main organic compound in solution, with a concentration of 12.3-15.7 mg/100 mL. The essential oil was than analyzed for the enantiomeric distribution of its monoterpene constituents, affording the following enantiomeric excesses in two beta-cyclodextrin-based enantioselective columns: (1S,5S)-(-)-alpha-pinene (60.0-69.6%), (1S,5S)-(-)-beta-pinene (5.2-7.2%), (R)-(-)-alpha-phellandrene (72.5-78.2%), (R)-(+)-limonene (28.6%) and (R)-(-)-linalool (1.8-3.1%).

An Assay on the Possible Effect of Essential Oil Constituents on Receptors Involved in Women's Hormonal Health and Reproductive System Diseases.[Pubmed:32567329]

J Evid Based Integr Med. 2020 Jan-Dec;25:2515690X20932527.

Aromatic herbal remedies, hydrosols, and essential oils are widely used for women's hormonal health. Scientific investigation of their major constituents may prevent unwanted infertility cases, fetal abnormalities, and drug-herb interactions. It also may lead to development of new medications. A list of 265 volatile molecules (mainly monoterpenes and sesquiterpenes) were prepared from a literature survey in Scopus and PubMed (2000-2019) on hydrosols and essential oils that are used for women's hormonal and reproductive health conditions. The PDB (protein data bank) files of the receptors (136 native PDB files) that involve with oxytocin, progesterone, estrogen, prolactin, acetyl choline, androgen, dopamine, human chorionic gonadotropin, luteinizing hormone, follicle-stimulating hormone, aromatase, and HER2 receptors were downloaded from Protein Data Bank. An in silico study using AutoDock 4.2 and Vina in parallel mode was performed to investigate possible interactions of the ligands with the receptors. Drug likeliness was investigated for the most active molecules using DruLiTo software. Aristola-1(10),8-diene, bergapten (5-methoxypsoralen), alpha-bergamotene, bicyclogermacrene, alpha-bisabolol oxide A, alpha-bisabolone oxide, p-cymen-8-ol, 10-epi elemol, alpha-elemol, beta-eudesmol, 7-epi-beta-eudesmol, ficusin, beta-humulene, methyl jasmonate, nerolidol, pinocarvone, (+)-spathulenol, and thujone had better interactions with some androgen, aromatase, estrogen, progesterone, HER2, AChR, and/or dopamine receptors. Most of these molecules had an acceptable drug likeliness except for alpha-bergamotene, bicyclogermacrene, beta-humulene, and aristola-1(10),8-diene. Some volatile natural molecules can be considered as lead compound for drug development to treat hormonal conditions.

Generation of flavor compounds by biotransformation of genetically modified hairy roots of Hypericum perforatum (L.) with basidiomycetes.[Pubmed:32566198]

Food Sci Nutr. 2020 Apr 16;8(6):2809-2816.

Altogether, 14 basidiomycetes (12BAD, 95PCH, 9WCOC, 5PSA, 96BCI, 331SHIBD, 4MSC, 74HFA, 220MPS, 115PFLA, 111 ICO C, 16LED, 6TSU, and 61LYP) were grown on solid and in liquid media using hairy roots of genetically modified Hypericum perforatum (L.) as the only source of carbon and nitrogen. After the first screening by GC-MS/MS-O, two fungi (115PFLA and 61LYP) which resulted in the most pleasant complex natural flavor by biotransformation were selected for further analysis. Twenty-four new volatile compounds were produced, from which 21 were identified (ethyl hexanoate, ethyl octanoate, benzaldehyde, 2-undecanone, (E,E)-2,4-decadienal, 1-octen-3-one, (E)-2-nonenal, ethyl nonanoate, 2-heptenal, 1-methoxy-4-methylbenzene, 3-octanone, 1-decen-3-one, (E)-2-octenal, 1-octen-3-ol, beta-linalool, +/-trans-nerolidol, anisole, methyl benzoate, 2-pentylfuran, 1,3-dichloro-2-methoxybenzene, and 1-dodecanol). Thereof, 15 compounds were perceived at the ODP, from which 13 were identified. Compound identification was performed by comparison of Kovats indices (KI) and mass spectra to those of authentic reference compounds on a polar VF-WAXms column using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS).

Effects of liming on the flavor of kokuto-shochu, a spirit made from non-centrifugal sugar.[Pubmed:32561073]

J Biosci Bioeng. 2020 Jun 16. pii: S1389-1723(20)30230-9.

Kokuto-shochu is a traditional Japanese spirit prepared from kokuto, a non-centrifugal brown cane sugar. When manufacturing kokuto, lime is added to the sugarcane juice to accelerate the crystallization of sucrose. Although the liming process differs depending on the manufacturer, the effects of liming on the quality of kokuto-shochu are unclear. Therefore, we investigated the flavor characteristics and volatiles present in kokuto-shochu prepared from kokuto with different liming degrees. Kokuto-shochu prepared from kokuto without liming had a pronounced kokuto-like flavor with a rich taste and contained higher contents of nerolidol, nonanal, acetoin, beta-damascenone, and 4-hydroxy-2,5-dimethyl-3(2H)-furanone compared to that prepared from kokuto with liming. On the other hand, kokuto-shochu prepared from kokuto with excess liming had a comparative grassy flavor. It contained higher esters, 4-vinylguaiacol, and pyrazines compared to other shochu. The levels nerolidol, isoamyl acetate, nonanal, and acetoin were affected by the mash pH during fermentation, and thus, liming would affect the formation of such volatiles via changing the mash pH. In contrast, pyrazines, 4-vinylguaiacol, and 4-hydroxy-2,5-dimethyl-3(2H)-furanone were not affected by mash pH, and their levels in the kokuto-shochu were consistent with those in kokuto raw materials. These results suggested that the liming process affects the levels of volatiles in kokuto-shochu by changing the mash pH and volatile levels in kokuto raw materials.

Chemical composition of essential oils from four Piper species, differentiation using multivariate analysis and antioxidant activity.[Pubmed:32496135]

Nat Prod Res. 2020 Jun 4:1-4.

Essential oils from the leaves of four species of Piper obtained through hydrodistillation were analyzed using GC-MS andmultivariate data analysis. The chemical analysis enabled the identification of qualitative and quantitative differences among the oils. beta-selinene (32.44 +/- 1.14%), (E)-nerolidol (44.23 +/- 2.23%), beta-caryophyllene (19.11 +/- 0.40%) and caryophyllene oxide (16.92 +/- 0.21%) were identified as the major constituents of the P. mollipilosum, P. brachypetiolatum, P. glandulosissimum and P. madeiranum oils, respectively. The differences in the chemical profiles of the oils were confirmed by principal component analysis. All four species exhibited antioxidant activity. The oil from P. brachypetiolatum achieved the best results on the DPPH test (EC50 = 64.8 microg/ml) and with the ABTS radical (EC50 = 159.7 microg/ml).

Cannabis sativa L. Inflorescences from Monoecious Cultivars Grown in Central Italy: An Untargeted Chemical Characterization from Early Flowering to Ripening.[Pubmed:32326129]

Molecules. 2020 Apr 20;25(8). pii: molecules25081908.

The chemical composition of the inflorescences from four Cannabis sativa L. monoecious cultivars (Ferimon, Uso-31, Felina 32 and Fedora 17), recently introduced in the Lazio Region, was monitored over the season from June to September giving indications on their sensorial, pharmaceutical/nutraceutical proprieties. Both untargeted (NMR) and targeted (GC/MS, UHPLC, HPLC-PDA/FD and spectrophotometry) analyses were carried out to identify and quantify compounds of different classes (sugars, organic acids, amino acids, cannabinoids, terpenoids, phenols, tannins, flavonoids and biogenic amines). All cultivars in each harvesting period showed a THC content below the Italian legal limit, although in general THC content increased over the season. Citric acid, malic acid and glucose showed the highest content in the late flowering period, whereas the content of proline drastically decreased after June in all cultivars. Neophytadiene, nerolidol and chlorogenic acid were quantified only in Felina 32 cultivar, characterized also by a very high content of flavonoids, whereas alloaromadendrene and trans-cinnamic acid were detected only in Uso-31 cultivar. Naringenin and naringin were present only in Fedora 17 and Ferimon cultivars, respectively. Moreover, Ferimon had the highest concentration of biogenic amines, especially in July and August. Cadaverine was present in all cultivars but only in September. These results suggest that the chemical composition of Cannabis sativa L. inflorescences depends on the cultivar and on the harvesting period. Producers can use this information as a guide to obtain inflorescences with peculiar chemical characteristics according to the specific use.

Overexpression of LiTPS2 from a cultivar of lily (Lilium 'Siberia') enhances the monoterpenoids content in tobacco flowers.[Pubmed:32278293]

Plant Physiol Biochem. 2020 Jun;151:391-399.

Lily, a famous cut flower with highly fragrance, has high ornamental and economic values. Monoterpenes are the main components contributing to its fragrance, and terpene synthase (TPS) genes play critical roles in the biosynthesis of monoterpenoids. To understand the function of TPS and to explore the molecular mechanism of floral scent in cultivar Lilium 'Siberia', transcriptomes of petal at different flowering stages and leaf were obtained by RNA sequencing and three unigenes related to TPS genes were selected for further validation. Quantitative real-time PCR showed that the expression level of LiTPS2 was greater than that of the other two TPS genes. Phylogenetic analysis indicated that LiTPS2 belonged to the TPSb subfamily, which was responsible for monoterpenes synthesis. Subcellular localization demonstrated that LiTPS2 was located in the chloroplasts. Furthermore, functional characterization showed that LiTPS2 utilized both geranyl pyrophosphate (GPP) and farnesyl pyrophosphate (FPP) to produce monoterpenoids such as linalool and sesquiterpenes like trans-nerolidol, respectively. Ectopic expression in transgenic tobacco plants suggested that the amount of linalool from the flowers of transgenic plants was 2-3 fold higher than that of wild-type plants. And the emissions of myrcene and (E)-beta-ocimene were also accumulated from the flowers of LiTPS2 transgenic lines. Surprisingly, these three compounds were the main fragrance components of oriental lily hybrids. Our results indicated that LiTPS2 contributed to the production of monoterpenes and could effectively regulate the aroma of Lilium cultivars, laying the foundation for biotechnological modification of floral scent profiles.

Composition and Biosynthesis of Scent Compounds from Sterile Flowers of an Ornamental Plant Clematis florida cv. 'Kaiser'.[Pubmed:32276485]

Molecules. 2020 Apr 8;25(7). pii: molecules25071711.

Clematis florida is a popular ornamental vine species known for diverse colors and shapes of its flowers but not for scent. Here we investigated the composition and biosynthesis of floral scent in 'Kaiser', a fragrant cultivar of C. florida that has sterile flowers. Volatile profiling revealed that flowers of 'Kaiser' emit more than 20 compounds, with monoterpenes being most abundant. Among the three floral organs, namely sepals, transformed-petals, and ovaries, ovaries had the highest rates of total volatile emission. To determine the molecular mechanism underlying floral scent biosynthesis in 'Kaiser', we sequenced a flower transcriptome and searched the transcriptome for terpene synthase genes (TPSs), which are key genes for terpene biosynthesis. Among the TPS genes identified, three were putative intact full-length genes and were designated CfTPS1, CfTPS2, and CfTPS3. Phylogenetic analysis placed CfTPS1, CfTPS2, and CfTPS3 to the TPS-g, TPS-b, and TPS-a subfamily, respectively. Through in vitro enzyme assays with Escherichia coli-expressed recombinant proteins, both CfTPS1 and CfTPS2 were demonstrated to catalyze the conversion of geranyl diphosphate to linalool, the most abundant constituent of C. florida floral scent. In addition, CfTPS1 and CfTPS2 produced the sesquiterpene nerolidol from (E,E)-farnesyl diphosphate. CfTPS3 showed sesquiterpene synthase activity and produced multiple products in vitro. All three CfTPS genes showed higher levels of expression in sepals than those in transformed-petals and ovaries. Our results show that despite being sterile, the flowers of 'Kaiser' have normal mechanisms for floral scent biosynthesis that make the flowers fragrant.

Induction of priming by cold stress via inducible volatile cues in neighboring tea plants.[Pubmed:32275096]

J Integr Plant Biol. 2020 Apr 10.

Plants have evolved sophisticated defense mechanisms to overcome their sessile nature. However, if and how volatiles from cold-stressed plants can trigger interplant communication is still unknown. Here, we provide the first evidence for interplant communication via inducible volatiles in cold stress. The volatiles, including nerolidol, geraniol, linalool, and methyl salicylate, emitted from cold-stressed tea plants play key role(s) in priming cold tolerance of their neighbors via a C-repeat-binding factors-dependent pathway. The knowledge will help us to understand how plants respond to volatile cues in cold stress and agricultural ecosystems.

(E)-Nerolidol is a volatile signal that induces defenses against insects and pathogens in tea plants.[Pubmed:32257238]

Hortic Res. 2020 Apr 1;7:52.

Plants release large amounts of volatile organic compounds (VOCs) in response to attackers. Several VOCs can serve as volatile signals to elicit defense responses in undamaged tissues and neighboring plants, but many questions about the ecological functions of VOCs remain unanswered. Tea plants are impacted by two harmful invaders, the piercing herbivore Empoasca (Matsumurasca) onukii Matsuda and the pathogen Colletotrichum fructicola. To determine the VOC signals in tea, we confirmed CsOPR3 as a marker gene and set up a rapid screening method based on a 1.51 kb CsOPR3 promoter fused with a beta-glucuronidase (GUS) reporter construct (OPR3p::GUS) in Arabidopsis. Using this screening system, a terpenoid volatile (E)-nerolidol was identified as a potent signal that elicits plant defenses. The early responses triggered by (E)-nerolidol included the activation of a mitogen-activated protein kinase and WRKY, an H2O2 burst, and the induction of jasmonic acid and abscisic acid signaling. The induced plants accumulated high levels of defense-related chemicals, which possessed broad-spectrum anti-herbivore or anti-pathogen properties, and ultimately triggered resistance against Empoasca onukii and Colletotrichum fructicola in tea. We propose that these findings can supply an environmentally friendly management strategy for controlling an insect pest and a disease of tea plants.

[Cloning and expression analysis of 5-phosphomevalonate kinase gene (CcPMK) in Cinnamomum camphora].[Pubmed:32237414]

Zhongguo Zhong Yao Za Zhi. 2020 Jan;45(1):78-84.

The 5-phosphomevalonate kinase(PMK) is a key enzyme in mevalonate(MVA) pathway which reversibly catalyzes the phosphorylation of mevalonate 5-phosphate(MVAP) to form mevalonate-5-diphosphate(MVAPP) in the presence of ATP and divalent metal ion such as Mg~(2+). In this research, on the basis of the transciptome database of Cinnamomum camphora, the PMK was cloned by cDNA from C. camphora, and was named CcPMK(GenBank number KU886266). The ORF of CcPMK was composed of 1 545 bp, encoding 514 amino acids. The bioinformatics analysis of CcPMK indicated that the molecular weight of the encoded protein was 56.14 kDa, with a theoretically isoelectric point of 7.64, and there was no signal peptide and transmembrane structure in putative protein. By multiple sequence alignment and phylogenetic tree analysis, we found that similarity between CcPMK and PMK amino acid sequence of other plants was as high as 75%. Among the similar sequences, 45% of them belonged to the alpha helix, while 16% belonged to the beta strand. CcPMK obtained 3 PMK protein family motifs and 1 ATP binding site Gly-Leu-Gly-Ser-Ser-Ala-Ala, and its 3 D structure contained a catalytic pocket structure, proving CcPMK as a member of PMK gene family. The result of phylogenetic tree showed that CcPMK was closely related to monocotyledon plants such as Phonenix dactylifera. The results of the Real-time PCR indicated that the expression level of CcPMK in borneol type was higher than that in linalool type, cineol type, iso-nerolidol type and camphor type. CcPMK expressed highest in roots and lowest in branches. Our results revealed that the expression level of CcPMK was different among five chemical types and different plant tissues, and the research provides foundation for further study of the terpenoids biosynthetic pathway in C. camphora.

Chemodiversity of Essential Oils from Nine Species of Celastraceae.[Pubmed:32222029]

Chem Biodivers. 2020 May;17(5):e2000107.

Extracts and compounds obtained from several species of Celastraceae family are reported as potential sources of drugs due to their diverse pharmacological properties. Nevertheless, essential oil composition from these species is still little known. This work aimed at the analysis of essential oils obtained from different Brazilian Celastraceae species. A total of seventeen oils were obtained using hydrodistillation process and analyzed by gas chromatography/mass spectrometry (GC/MS). Principal component analysis (PCA) allowed the identification of a chemical composition pattern among the analyzed essential oils. Some compounds were more frequent among Celastraceae species, such as cis- and trans-linalool oxide (14/17 oil samples), nerylacetone (13/17), linalool (11/17), beta-ionone (10/17), alpha-ionone (9/17), nerolidol (10/17), decanal (10/17), and dodecanoic acid (10/17). These results contribute to the chemophenetics of Celastraceae species.

Ameliorative effect of nerolidol on cyclophosphamide-induced gonadal toxicity in Swiss Albino mice: Biochemical-, histological- and immunohistochemical-based evidences.[Pubmed:32048763]

Andrologia. 2020 May;52(4):e13535.

Cyclophosphamide (CP) is commonly used as antineoplastic and immunosuppressant drug with noticeable gonadotoxic profile. Nerolidol (NER) is a sesquiterpene with potent antioxidant and anti-inflammatory properties. Thus, the present study was designed to explore its possible gonadal protective potential against cyclophosphamide-induced testicular, epididymal, seminal and spermatozoal toxicities. Animals were divided into five groups: control (normal saline for 14 days), treatment group (NER 200 and 400 mg/kg, p.o) for 14 days along with a single dose of cyclophosphamide (200 mg/kg, i.p) on 7(th) day, toxic and Per se groups (cyclophosphamide 200 mg/kg i.p) on 7(th) day and NER 400 mg/kg for 14 days respectively. Animals were sacrificed on the 15 day, and body weight, weight of reproductive organs, testosterone level, sperm count, biochemical parameters, histopathological and immunohistochemical studies were performed in the testes, epididymis and in the serum. CP administration induced oxidative stress, nitrative stress, inflammation, reduced testosterone level, sperm count, increased expression of MPO and caused histological aberrations in the testes, epididymis and seminal vesicles. CP caused reduced sperm count, sperm motility and testosterone level which got reversed upon treatment with nerolidol in a dose-dependent manner. Nerolidol thus acted as a gonadoprotective molecule and prevented the gonadotoxicity of CP.