Search Results (94)

Monoterpenes and their derivatives are important starting compounds in the design of new biologically active substances. In particular, cineole, isolated from eucalyptus essential oil, exhibits a wide range of biological activities. Here, the synthesis of new heterocyclic compounds containing a cineole fragment by the acid-catalyzed condensation of α-pinene-derived 8-hydroxy-6-hydroxymethyllimonene with monoterpene aldehydes was carried out for the first time. The reactions of 8-hydroxy-6-hydroxymethyllimonene with cuminaldehyde, perillylaldehyde, myrtenal, citral, and geranial were studied in the presence of heterogeneous K10 clay or Lewis acid BF₃·Et₂O. The main products of these reactions were compounds with the methanopyrano[4,3-b]pyran scaffold having a 1,8-cineole fragment. As a result of this work, five new compounds with the methanopyrano[4,3-b]pyran scaffold were synthesized. The use of BF₃·Et₂O led to an increase in the yields of target products, compared with the results obtained on K10 clay. Full article

This study evaluated the physiological and biochemical responses of chickpea (Cicer arietinum L.) to foliar application of cineole, carvacrol, and thymol at concentrations of 500 and 1000 ppm. Carvacrol at 1000 ppm significantly enhanced fresh biomass (+15.4%) and aerial biomass (+46.2%), whereas thymol significantly reduced plant height (−20.2%) and overall biomass, yet notably increased chlorophyll content (+23.3%) and vitamin C levels (+41.4%) at the same concentration. Cineole significantly improved antioxidant capacity by increasing total phenolic content (+15.5% at 1000 ppm) and total flavonoid content (+19.1% at 500 ppm), but simultaneously decreased soluble protein synthesis and chlorophyll content (−39% at 500 ppm). Mineral analysis showed notable increases in calcium content following treatment with cineole (+30.5% at 1000 ppm) and carvacrol (+32% at 500 ppm), while thymol at 1000 ppm significantly reduced phosphorus, potassium, manganese, iron, copper, and zinc accumulation. Molecular docking and dynamic simulations revealed strong interactions of thymol and carvacrol with essential enzymes, specifically ascorbate peroxidase and phenylalanine ammonia-lyase, which are involved in antioxidant and phenolic metabolism pathways. These molecular interactions suggest potential contributions of thymol and carvacrol to plant stress resilience mechanisms, although further experimental validation is needed to confirm their roles in vivo. These findings emphasize the importance of optimizing monoterpene concentrations, indicating that carefully calibrated treatments could effectively enhance chickpea growth, nutritional quality, and stress tolerance within sustainable agricultural practices. Full article

Achillea nobilis and its subspecies (A. nobilis subsp. neilreichii and A. nobilis subsp. sipylea) have been traditionally used in various ethnomedical systems across Eurasia. However, comprehensive studies on their phytochemical composition and pharmacological properties are still insufficient. This review aims to provide a critical synthesis of current knowledge regarding the botanical characteristics, geographic distribution, traditional applications, chemical constituents, and pharmacological effects of A. nobilis A structured search was conducted using eight scientific platforms, including Scopus, PubMed, Web of Science, Google Scholar, Science.gov, ScienceDirect, JSTOR, and BASE. Keywords related to phytochemistry, pharmacology, and ethnomedicine were applied, and a total of 28,000 records were initially retrieved. After a multi-stage screening process based on inclusion and exclusion criteria, 167 peer-reviewed publications from 1952 to 2023 were selected for detailed evaluation. Findings reveal a diverse range of bioactive compounds, such as flavonoids, monoterpenes, sesquiterpenes, and sesquiterpene lactones, which demonstrate antioxidant, antimicrobial, anti-inflammatory, antinociceptive, antispasmodic, and anticonvulsant activities. Most studies have focused on aerial parts and water-based extracts, while the root chemistry and organ-specific metabolite profiles remain largely unexplored. This review highlights the therapeutic potential of A. nobilis and underscores the need for future studies using multi-omics and advanced analytical techniques to support its development in pharmaceutical and nutraceutical applications. Full article

Aroma is an important processing and consumption quality trait of fruits and vegetables, and terpenes produced from the terpenoid metabolic pathway are a critical component of chili fruit flavor. This pathway involves the participation of at least eighteen enzymes, such as AACT, HMGS, HMGR, MVK, PMK, MVD, FPPS, GGPPS, DXS, DXR, MCT, CMK, MECPS, HDS, HDR, GPPS, IDI, and TPS. In this study, the genome wide information, expression characteristics, and relationship with terpenoids of terpenoid pathway genes are analyzed in C. annuum. The results showed that C. annuum has sixty-seven genes related to terpene metabolic pathways. Non-targeted metabolomics studies found that the content of aromatic terpenoids α-calacorene, α-cubene, and cis-β-farnesene increased with fruit development in HDL fruits, while linalool and nerolidol were much higher in GLD608. Correlation analyses between qRT-PCR and metabolome data showed that the expression levels of CaHMGS-3, CaMVD-1, CaCMK-1, and CaGGPPS-2 were positively correlated with the content of linalool, a flavor monoterpene alcohol. CaMECPS-1 was positively correlated with cis-β-farnesene, and there was also a significant positive regulatory relationship between CaTPS-5 and nerolidol relationship. In conclusion, the present study provides genetic resources for further studies on the gene regulatory mechanisms of flavor synthesis and terpenoid metabolic pathways in chili. Full article

Flower fragrance is a crucial ornamental and economic trait of Dendrobium chrysotoxum, and the most abundant and diverse aroma-active compounds are terpenes. Terpene synthase (TPS) is the ultimate enzyme for the biosynthesis of various types of terpenes, and TPS genes were identified as the key regulators governing the spatiotemporal release of volatile terpene compounds. Until recently, the TPS gene family in D. chrysotoxum has remained largely unexplored. Our study characterizes the TPS genes in D. chrysotoxum and identifies 37 DcTPS gene family members. It helped identify the DcTPS genes, gene characteristics, the phylogeny relationship, conserved motif location, gene exon/intron structure, cis-elements in the promoter regions, protein–protein interaction (PPI) network, tissue specific expression and verification of the expression across different flowering stages and floral organs. Three highly expressed DcTPS genes were cloned, and their functions were verified using a transient expressed in tobacco leaves. Further functional verification showed that the proteins encoded by these genes were enzymes involved in monoterpene synthesis, and they were all involved in the synthesis of linalool. This study comprehensively expatiates on the TPS gene family members in D. chrysotoxum for the first time. These data will help us gain a deeper understanding of both the molecular mechanisms and the effects of the TPS genes. Furthermore, the discovery that three TPS-b genes (DcTPS 02, 10, 32) specifically drive linalool-based scent in D. chrysotoxum, will provide new insights for expanding the TPS-b subfamily in orchids and identifying the linalool synthases contributing to orchid fragrance. Full article

Light is an important environmental regulator of plant secondary metabolism. Terpenoids, the most abundant secondary metabolites in plants, demonstrate a wide spectrum of biologically significant properties, encompassing antimicrobial, antioxidative, and analgesic activities. Litsea cubeba (Lour.) Pers., a core species within the Lauraceae family, exhibits notable pharmacological potential, including antimicrobial and antitumor effects. Here, we found that darkness treatment significantly suppressed terpenoid accumulation in L. cubeba fruits. To clarify the molecular mechanisms underlying the regulatory effect of light and darkness treatments on terpenoid biosynthesis, we conducted a comparative transcriptome profiling of L. cubeba fruits under light and darkness treatments. A total of 13,074 differentially expressed genes (DEGs) were identified among four sampling time points (L1-L2-L3-L4 vs. D1-D2-D3-D4). These genes were enriched in various pathways, with significant enrichment being observed in the terpenoid and other secondary metabolism pathways. Additionally, the enrichment of DEGs in L2 and D2 stages was further studied, and it was found that nine DEGs were significantly enriched in the monoterpene synthesis pathway. The weighted gene co-expression network analysis (WGCNA) showed that alcohol dehydrogenase (ADH), a key enzyme in terpenoid synthesis, had the same expression pattern as WRKY and NAC transcription factors, suggesting their involvement in the biosynthesis of terpenoids in L. cubeba. Expression profiling demonstrated that plastid-localized terpenoid pathway genes were markedly downregulated under darkness treatment. qRT-PCR validation of key genes (LcDXS3, LcHMGS1, LcMDS, and LcTPS19) confirmed the reliability of the transcriptome data, with LcDXS3 exhibiting pronounced declines in expression after 6 h (2.76-fold decrease) and 12 h (2.63-fold decrease) of darkness treatment. These findings provide novel insights into the photoregulatory mechanisms governing terpenoid metabolism in L. cubeba. Full article

Neo-allo-ocimene is a monoterpene which could be applied in pesticides, fragrances, and sustainable polymers. In this study, we mined a terpene synthase, AgTPS40, from the transcriptome of celery leaf tissues. Through sequence and phylogenetic analysis, AgTPS40 was characterized as a monoterpene synthase. The AgTPS40 gene was introduced into a heterologous mevalonate pathway hosted in Escherichia coli to enable terpene production. Gas chromatography–mass spectrometry analysis confirmed that AgTPS40 catalyzes the formation of neo-allo-ocimene, marking the first reported identification of a neo-allo-ocimene synthase. Subsequently, we optimized the fermentation conditions and achieved a yield of 933.35 mg/L in a 1 L shake flask, which represents the highest reported titer of neo-allo-ocimene to date. These results reveal the molecular basis of neo-allo-ocimene synthesis in celery and provide a sustainable way to obtain this compound. Full article

Low temperature stress represents a significant abiotic stress factor affecting rice yields. While the structure and some of the functions of cell cycle protein-dependent protein kinase inhibitor (CKI) family proteins have been the subject of study, their relevance to cold tolerance in rice has been less investigated. In this study, we cloned OsEL2 (LOC_Os03g01740) and constructed anti-expression lines of this gene. The resulting lines exhibited significant cold sensitivity and displayed greater oxidative damage than wild type Nippobare (Nip). However, the activities of antioxidant enzymes, such as catalase (CAT), were significantly elevated in OsEL2-AX plants in comparison to Nip following exposure to 4 °C stress. RNA sequencing revealed the presence of 18,822 differential genes, with the majority of them being expressed with temporal specificity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that a considerable number of differentially expressed genes (DEGs) are involved in the metabolism of amino acids, lipids, and terpenoids. Weighted gene co-expression network analysis (WGCNA) revealed a close relationship between the genes in the turquoise and light green modules and rice cold tolerance traits. These genes were predominantly enriched in terpene metabolism and the metabolism of various plant secondary metabolites, suggesting that OsEL2 influences rice cold tolerance through the metabolism of these two classes of substances. An analysis of the genes within these two modules using transcription factor (TF) enrichment and KEGG enrichment revealed that they are predominantly regulated by mitogen-activated protein kinase (MAPK) and ethylene signaling pathways. Furthermore, we found that tryptophan metabolism, phenylalanine metabolism, and monoterpene synthesis were enriched in down-regulated pathway enrichment analysis. In addition, we also found that the MAPK signaling pathway was enriched in the KEGG enrichment analysis of AX2 with Nip. The results demonstrate that anti-expression of OsEL2 is associated with a notable decline in rice tolerance to cold stress. Full article

Perillic acid (PA) is a limonene derivative in which the exocyclic methyl is oxidized to a carboxyl group. Although endowed with potential anticancer activity, PA has been much less explored regarding its biological properties than analogous compounds such as perillyl alcohol, perillaldehyde, or limonene itself. PA is usually described in mixture with alcohols and ketones produced in the oxidation of monoterpenes, with relatively few existing reports focusing on the PA molecule. This study provides a comprehensive review of PA, addressing its origin, the processes of obtaining it through organic synthesis and biotransformation, and the pharmacological tests in which it is either the lead compound or reference for in vitro efficacy in experimental models. Although feasible and generally poorly yielded, the synthesis of PA from limonene requires multiple steps and the use of unusual catalysts. The most economical process involves using (−)-β-pinene epoxide as the starting material, ending up with (−)-PA. On the other hand, some bacteria and yeasts are successful in producing, exclusively or at satisfactory purity level, PA from limonene or a few other monoterpenes, through environmentally friendly approaches. The compiled data revealed that, with few exceptions, most reports on PA bioactivity are related to its ability to interfere with the prenylation process of oncogenic proteins, an essential step for the growth and dissemination of cancer cells. The present survey reveals that there is still a vast field to disclose regarding the obtaining and scaling of PA via the fermentative route, as well as extending prospective studies on its properties and possible pharmacological applications, especially in the preclinical oncology field. Full article

Terpenes are critical components of the floral fragrance component in Dendrobium chrysotoxum, synthesized by terpene synthase (TPS). Analysis of the D. chrysotoxum genome and transcriptional data revealed that the gene DcTPSb1 was significantly up-regulated during flowering periods, showing a strong correlation with the accumulation of aromatic monoterpenes in the floral components of Dendrobium chrysotoxum. Consequently, the DcTPSb1 gene was selected for further analysis. DcTPSb1 exhibited elevated expression levels in flowers among four organs (roots, stems, leaves, flowers) of D. chrysotoxum, with the highest expression observed during the blooming phase, which aligned with the accumulation of volatile terpenes during flowering. DcTPSb1, located in the chloroplasts, was identified as a member of the TPS-b subfamily associated with monoterpenes synthesis, showing close phylogenetic relationships with homologous proteins in related plant species. An analysis of the promoter region of DcTPSb1 indicated that it may be regulated by methyl jasmonate (MeJA) responsiveness. Functionally, DcTPSb1 was shown to catalyze the conversion of geranyl diphosphate (GPP) to linalool, ocimene, and (-)-α-pinitol in vitro. Overexpression of DcTPSb1 in tobacco resulted in a significant increase in terpenoid release during the blooming stage; however, the up-regulated substances did not include their catalytic products. The classification of DcTPSb1 as a terpene synthase capable of producing multiple products provides valuable insights into the complex biosynthesis of terpenes in orchids. These findings enhance our understanding of the functional diversity of DcTPSb1 and the processes involved in terpene biosynthesis in orchids. Full article

Background: Lipoxygenases (LOXs) are key enzymes in the unsaturated fatty acid oxidation reaction pathway and play an important regulatory role in the synthesis of fruit aroma volatiles. Methods: LOX gene family members were identified in the whole genome database of bitter gourd and analyzed bioinformatically. An RT-qPCR was used to analyze the expression differences in different tissues. Monoterpenes were determined by gas chromatography-mass spectrometry (GC-MS) technique. Results: A total of 12 LOX gene family members were identified in the genome. The expression of LOX genes varied significantly among the tissues of roots, stems, leaves, flowers, fruits, seeds and tendrils. A total of 29 monoterpenes were detected in the fruits of five different fruit colors of bitter gourd, mainly containing six types of alcohols, aldehydes, terpenes, ketones, esters and alkynes, with the highest relative content of alcohols. Conclusions: The present study provides a reference for further elucidation of the biological functions of the LOX gene in the synthesis pathway of aroma volatiles in bitter gourd. Full article

Background: CPT is a pentacyclic monoterpene alkaloid with a wide spectrum of antitumor activity. Its clinical application is restricted due to poor water solubility, instability, and high toxicity. We developed a new kind of multifunctional micelles to improve its solubility, reduce the side effecs, and obtain enhanced antitumor effects. Methods: We constructed HA-CPT nano-self-assembly prodrug micelles, which combined the advantages of pH-sensitivity, redox-sensitivity, and active targeting ability to CD44 receptor-overexpressing cancer cells. To synthesize dual sensitive HA-CPT conjugates, CPT was conjugated with HA by pH-sensitive histidine (His) and redox-sensitive 3,3′-dithiodipropionic acid (DTPA). In vitro, we studied the cellular uptake and antitumor effect for tumor cell lines. In vivo, we explored the bio-distribution and antitumor effects of the micelles in HCT 116 tumor bearing nude mice. Results: The dual-sensitive and active targeting HA-His-ss-CPT micelles was proved to be highly efficient in CPT delivery by the in vitro cellular uptake study. The HA-His-ss-CPT micelles escaped from endosomes of tumor cells within 4 h after cellular uptake due to the proton sponge effect of the conjugating His and then quickly released CPT in the cytosol by glutathione (GSH). In mice, HA-His-ss-CPT micelles displayed efficient tumor accumulation and conspicuous inhibition of tumor growth. Conclusions: The novel, dual-sensitive, active targeting nano-prodrug micelles exhibited high efficiency in drug delivery and cancer therapy. This “all in one” drug delivery system can be realized in an ingenious structure and avoid intricate synthesis. This construction strategy can illume the design of nanocarriers responding to endogenous stimuli in tumors. Full article

Lauraceae, an important family of Angiospermae, comprises over 2500 species widely distributed in tropical and subtropical evergreen broad-leaved forests. This family is renowned for its rich resource of terpenoids, particularly monoterpenes, sesquiterpenes, and diterpenes. These compounds not only impart specific scents to Lauraceae species but also play crucial roles in plant growth, development, and environmental adaptation. These compounds also possess extensive bioactivities, such as antioxidant, antibacterial, anti-inflammatory, and neuroprotective effects, making them valuable in the fields of perfumery, cosmetics, food, and medicine, and thus holding significant economic value. Recent advancements in high-throughput technologies, especially genomics, transcriptomics, and metabolomics, have significantly advanced our knowledge of the chemical constituents and biosynthetic pathways of terpenoids in Lauraceae species. Such progress has also shed light on the diversity and functionality of the terpene synthases (TPSs) gene family, a key enzyme involved in terpenoid biosynthesis. This paper reviews the latest research findings on the biosynthetic pathways of terpenoids and their key enzyme-encoding gene families in Lauraceae plants. We also analyze the evolutionary patterns of TPS gene family members of four Lauraceae species at the whole-genome level and summarize their mechanisms of action in secondary metabolite synthesis. Furthermore, this paper highlights the current research challenges and proposes prospects, such as the complexity of gene families, the uncertainties in functional predictions, and unclear regulatory mechanisms. Our objective is to provide scientific foundations for the in-depth analysis of terpenoid biosynthesis mechanisms and the development and utilization of natural products in Lauraceae plants. Full article

Plant defence mechanisms, including physical barriers like toughened bark and chemical defences like allelochemicals, are essential for protecting them against pests. Trees allocate non-structural carbohydrates (NSCs) to produce secondary metabolites like monoterpenes, which increase during biotic stress to fend off pests like the Eurasian spruce bark beetle, ESBB (Ips typographus). Despite these defences, the ESBB infests Norway spruce, causing significant ecological damage by exploiting weakened trees and using pheromones for aggregation. However, the mechanism of sensing and resistance towards host allelochemicals in ESBB is poorly understood. We hypothesised that the exposure of ESBB to spruce allelochemicals, especially monoterpenes, leads to an upsurge in the important detoxification genes like P450s, GSTs, UGTs, and transporters, and at the same time, genes responsible for development must be compromised. The current study demonstrates that exposure to monoterpenes like R-limonene and sabiene effectively elevated detoxification enzyme activities. The differential gene expression (DGE) analysis revealed 294 differentially expressed (DE) detoxification genes in response to R-limonene and 426 DE detoxification genes in response to sabiene treatments, with 209 common genes between the treatments. Amongst these, genes from the cytochrome P450 family 4 and 6 genes (CP4 and CP6), esterases, glutathione S-transferases family 1 (GSTT1), UDP-glucuronosyltransferase 2B genes (UDB), and glucose synthesis-related dehydrogenases were highly upregulated. We further validated 19 genes using RT-qPCR. Additionally, we observed similar high expression levels of detoxification genes across different monoterpene treatments, including myrcene and α-pinene, suggesting a conserved detoxification mechanism in ESBB, which demands further investigation. These findings highlight the potential for molecular target-based beetle management strategies targeting these key detoxification genes. Full article