Major Sesquiterpene Research Articles

Costunolide improved dextran sulfate sodium-induced acute ulcerative colitis in mice through NF-κB, STAT1/3, and Akt signaling pathways

Costunolide (CTL) is the major sesquiterpene lactone from Radix Aucklandiae, which is widely used on the treatment of gastrointestinal diseases. However, the therapeutic effect of costunolide in ulcerative colitis (UC) is still unknown. Herein, we sought to evaluate the therapeutic effects and underlying mechanisms of costunolide on UC. ICR mice were intraperitoneally administered with costunolide (10 mg/kg) for 10 days. Beginning on the 4th day of drug administration, acute colitis was induced by feeding 4% dextran sulfate sodium (DSS) for additional 7 days. Costunolide markedly attenuated DSS-induced body weight loss, colonic shortening, elevation in disease activity index, and pathological damage of colon, and decreased the number of CD4+ T cells in colon tissues. Furthermore, costunolide significantly inhibited myeloperoxidase (MPO) activity and nitric oxide (NO) level in colon tissues in DSS-exposed mice. Meanwhile, costunolide also suppressed DSS-induced expression of induced nitric oxide synthase (iNOS), interleukin-1β (IL‐1β), IL‐6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in both mRNA and protein levels. Mechanistically, costunolide repressed the phosphorylation of nuclear factor kappa-B (NF-κB) p65 and degradation of inhibitor of NF-κB (IκB), as well as the excessive activation of signal transducers and activators of transcription 1/3 (STAT1/3) and serine/threonine protein kinase Akt (Akt) in colon tissues in DSS-challenged mice. These findings successfully demonstrated that costunolide ameliorated DSS-induced murine acute colitis by suppressing inflammation through inactivation of NF-κB, STAT1/3, and Akt pathways. These results also suggested that costunolide may be a potential therapeutic agent for the treatment of acute UC.

Ferula hermonis: A Review of Current Use and Pharmacological Studies of its Sesquiterpene Ester Ferutinin

Ferula hermonis Boiss, is an endemic plant of Lebanon, locally known as "shilsh Elzallouh". It has been extensively used in the traditional medicine as an aphrodisiac and for the treatment of sexual impotence. Crude extracts and isolated compounds of ferula hermonis contain phytoestrogenic substances having a wide spectrum of in vitro and in vivo pharmacological properties including anti-osteoporosis, anti-inflammatory, anti-microbial and anti-fungal, anti-cancer and as sexual activity enhancer. The aim of this mini-review is to highlight the traditional and novel applications of this plant's extracts and its major sesquiterpene ester, ferutinin. The phytochemical constituents and the pharmacological uses of ferula hermonis crude extract and ferutinin specifically will be discussed.

Variation of sesquiterpene lactone contents in Lactuca altaica natural populations from Armenia

In recent years we initiated extensive studies on the characterization of the population structure of wild Lactuca relatives (WLRs) originating from their center of origin and diversity in Southwest Asia. A comparative phytochemical study of nine sesquiterpene lactones in natural populations of the wild lettuce L. altaica Fisch. & C.A. Mey. (Asteraceae) was performed, based on 22 plants, representing seven original individual seed samples derived from three localities representing three regions in Armenia. The compounds were profiled and quantified in leaves and roots of the plants, grown in a controlled glasshouse. The contents of major sesquiterpene lactones, that including the following eight guaianolides: cichorioside B, lactucin, 11β,13-dihydrolactucin, crepidiaside B, 8-deoxylactucin, jacquinelin, lactucopicrin/11β,13-dihydrolactucopicrin, as well as the germacranolide glucoside – lactuside A, were estimated by HPLC/PDA. The L. altaica plants could be characterized by the occurrence of lactuside A in their roots, and the mixture of lactucopicrin/11β,13-dihydrolactucopicrin in both their roots and leaves by relatively high amounts, similarly to results obtained for three commercial cultivars of L. sativa. The total content of sesquiterpene lactones in the roots was significantly higher than that in the leaves. This study is likely the first report of detailed screening of L. altaica natural populations and individuals, even by low sample size, for any trait. Species within the primary lettuce gene pool, should be considered as an attractive source of germplasm in further research and improvement of cultivated lettuce, Lactuca sativa L. While using interspecific hybridization in order to elevate the sesquiterpene levels in cultivated lettuces, the lactones quality (profile) and quantity, as well as the cross-ability level of the wild Lactuca spp. with the crop and fertility of the obtained offspring should be considered.

Efficacy and antiparasitic mechanism of curdione from Curcuma zedoaria against Gyrodactylus kobayashii in goldfish

Monogeneans are principally ectoparasites of fish with a global distribution and result in fish morbidity and mortality in aquaculture. Since current treatments mainly rely on the application of toxic or unapproved chemicals, there is an urgent need to identify new anthelmintic agents. In the present study, in vivo anthelminthic activities of 33 selected medicinal plants were investigated against Gyrodactylus kobayashii, a monogenean parasite infecting goldfish (Carassius auratus). The screening results showed that the methanol extracts of Curcuma zedoaria and Peucedanum praeruptorum had the highest activity against G. kobayashii. The concentration required to kill all parasites of two extracts was both 30 mg/L within 48 h of exposure, while C. zedoaria methanol extract showed lower toxicity to goldfish and was selected for the next study. Subsequently, two major sesquiterpene compounds from C. zedoaria, curdione and curcumenol were further tested for anthelminthic efficacy. The results revealed that only curdione demonstrated in vitro and in vivo antiparasitic effects, 12 mg/L killed 87.04% of G. kobayashii after 2 h in in vitro trials. And bathing G. kobayashii-infected goldfish in curdione induced significant reduction in a total worm burden, with EC50 values of 1.323 and 0.885 mg/L after 24 and 48-h immersion, respectively, and 100% efficacy was achieved at a concentration of 4.0 mg/L after 48 h. Furthermore, to gain insight into the plausible mechanism of anthelminthic activity of curdione, its effects on the ultrastructural alterations of G. kobayashii were performed in vivo by SEM which displayed obvious tegumental damages. Further confirmation of the significant declines of ATP contents in worms were obtained after both in vitro and in vivo treatments with curdione. These findings indicated that curdione mediated worm killing was associated with tegumental damages and energy insufficient. The results suggested that curdione has the potential as an alternative natural compound for the control of Gyrodactylus infections.

In vitro evaluation of anticaries, antimycobacterial, antileishmanial and cytotoxic activities of essential oils from Eremanthus erythropappus and of α-bisabolol, their major sesquiterpene

Interest in researches into medicinal plants and therapeutic effects of essential oils (EOs) on humans has increased over the last few years. Eremanthus erythropappus, known as candeia, is a Brazilian aromatic herbaceous plant whose α-bisabolol-rich oil has been used in several cosmetic preparations. This paper reports in vitro anticaries, antimycobacterial, antileishmanial and cytotoxic activities of EOs from E. erythropappus leaves (EL-EO) and stalks (ES-EO), besides α-bisabolol, their main sesquiterpene. EL-EO and ES-EO were extracted by hydrodistillation and analyzed by GC-FID and GC-MS. α-Bisabolol, cis-α-bisabolene and β-bisabolene were identified as their major constituents. Antibacterial activity of EOs was evaluated against eight standard strains of pathogens from the American Type Culture Collection (ATCC) by determining minimum inhibitory concentrations (MICs) with the use of the microdilution method. Antibacterial activity was evaluated against Streptococcus mutans, S. mitis, S. sanguinis, S. sobrinus, S. salivarius, Mycobacterium tuberculosis, M. avium and M. kansasii. EL-EO, ES-EO and α-bisabolol exhibited high leishmanicidal activity against promastigote forms of Leishmania amazonensis; IC50 values were 9.22 µg/mL, 6.00 µg/mL and 3.12 µg/mL, respectively. The 50% cytotoxic concentrations (CC50) of EL-EO, ES-EO and α-bisabolol against mouse peritoneal macrophages were 24.65 µg/mL, 8.87 µg/mL and 1021.00 µg/mL, respectively. These results suggest that EOs from E. erythropappus seem to be very promising for the development of new bactericidal and leishmanicidal agents.

Himachalol induces apoptosis in B16-F10 murine melanoma cells and protects against skin carcinogenesis

Ethnopharmacological relevanceCedrus libani A. Rich (C. libani) is majestic evergreen Mediterranean conifer growing in the mountains of Lebanon. The ethnobotanical and traditional uses of cedar wood oil traces back to ancient times for the treatment of various ailments including cancer. Previous work in our laboratories revealed that himachalol (7-HC), a major sesquiterpene isolated from C. libani, possesses potent cytotoxic activity against various human cancer cell lines as well as promising anti-inflammatory effect in isolated rat monocytes. Aim of the studyThe present study aims to elucidate the mechanism of action behind the cytotoxic activity of 7-HC against murine melanoma cells (B16F-10) and evaluates its chemopreventive effect against chemically-induced skin carcinogenesis in mice. Materials and methods7-HC was extracted and purified from Cedrus libani wood. Cell viability was evaluated using WST-1 kit. Cell cycle analysis and apoptosis were assessed by Flow cytometry using propidium iodide (PI) and fluorescein Isothiocyanate (FITC)-conjugated Annexin V/PI staining respectively. Apoptosis related protein were quantified using western blot. The chemopreventive activity of 7-HC was evaluated for 20 weeks using a DMBA/TPA induced skin carcinogenesis model in Balb/c mice. Results7-HC displayed a potent anti-proliferative activity against the melanoma cells with an IC50 of 8.8 μg/ml and 7.3 μg/ml at 24 and 48 h, respectively. Co-treatment with Cisplatin did not show any synergistic or additive effect on cell viability. Flow cytometry analysis using PI revealed that 7-HC treatment (5 and 10 μg/ml) induces the accumulation of cells in the sub-G1 phase and causes a decline in cell populations in the S and G2/M phases. Annexin/PI staining also reveals that 7-HC treatment significantly increases the percentage of cells undergoing early and late apoptosis. Western blot analysis shows that 7-HC treatment decreases the level of the anti-apoptotic protein Bcl-2 and increases the level of the pro-apoptotic protein Bax. A reduction in the level of phosphorylated Erk and Akt was also observed. 7-HC via topical (2.5%), intraperitoneal (10, 25 and 50 mg/kg) or gavage (50 mg/kg) treatment revealed a significant decrease in papilloma volume with no adverse effect on liver and kidney function. ConclusionsThe present study demonstrates that 7-HC treatment protects against chemically-induced skin carcinogenesis, promotes cell cycle arrest and induces apoptosis partially through an inhibition of both the MAPK/Erk and PI3K/Akt pathways.

Bioactivity of Essential Oil from Atalantia buxifolia Leaves and its Major Sesquiterpenes against Three Stored-Product Insects

The insecticidal and repellent activities of the essential oil (EO) from Atalantia buxifolia leaves were evaluated against three stored product insects, including Tribolium castaneum, Lasioderma serricorne and Liposcelis bostrychophila. The EO obtained by hydrodistillation was investigated by GC-FID and GC-MS. Twenty-four compounds were identified and the principal components in the EO were β-caryophyllene (25.8 %), caryophyllene oxide (19.1 %) and epiglobulol (7.5 %). In this paper, the bioactivity of the obtained EO and its two major components were investigated by contact and repellent activity bioassay. The EO showed significant contact activity against T. castaneum, L. serricorne and L. bostrychophila adults with LD50 values of 23.9 μg/adult, 15.2 μg/adult and 54.6 μg/cm2, respectively. And at the highest testing concentration (T. castaneum and L. serricorne: 78.63 nL/cm2; L. bostrychophila: 63.17 nL/cm2), the repellent effect of the EO on three target insects was comparable to that of the positive control (DEET) after 2 h of exposure. For components, β-caryophyllene and caryophyllene oxide showed different levels of contact and repellent activities against three target insects. These results suggest that the EO from A. buxifolia leaves and its two major components have potential to be developed as natural insecticides and repellents for the control of stored product insect pests.

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum.

Terpene synthases (TPSs) are pivotal enzymes for the production of diverse terpenes, including monoterpenes, sesquiterpenes, and diterpenes. In our recent studies, dictyostelid social amoebae, also known as cellular slime molds, were found to contain TPS genes for making volatile terpenes. For comparison, here we investigated Physarum polycephalum, a plasmodial slime mold also known as acellular amoeba. Plasmodia of P. polycephalum grown on agar plates were found to release a mixture of volatile terpenoids consisting of four major sesquiterpenes (α-muurolene, (E)-β-caryophyllene, two unidentified sesquiterpenoids) and the monoterpene linalool. There were no qualitative differences in terpenoid composition at two stages of young plasmodia. To understand terpene biosynthesis, we analyzed the transcriptome and genome sequences of P. polycephalum and identified four TPS genes designated PpolyTPS1–PpolyTPS4. They share 28–73% of sequence identities. Full-length cDNAs for the four TPS genes were cloned and expressed in Escherichia coli to produce recombinant proteins, which were tested for sesquiterpene synthase and monoterpene synthase activities. While neither PpolyTPS2 nor PpolyTPS3 was active, PpolyTPS1 and PpolyTPS4 were able to produce sesquiterpenes and monoterpenes from the respective substrates farnesyl diphosphate and geranyl diphosphate. By comparing the volatile profile of P. polycephalum plasmodia and the in vitro products of PpolyTPS1 and PpolyTPS4, it was concluded that most sesquiterpenoids emitted from P. polycephalum were attributed to PpolyTPS4. Phylogenetic analysis placed the four PpolyTPSs genes into two groups: PpolyTPS1 and PpolyTPS4 being one group that was clustered with the TPSs from the dictyostelid social amoeba and PpolyTPS2 and PpolyTPS3 being the other group that showed closer relatedness to bacterial TPSs. The biological role of the volatile terpenoids produced by the plasmodia of P. polycephalum is discussed.

Actualities in the phytochemical research on selected terpenes.

A short review of our recent research on the essential oil phytochemical composition of Petasites albus (L.) Gaertn. and Petasites hybridus (L.) G. Gaertn., B. Mey. & Scherb. (Asteraceae) as well as on the oils of Globularia cordifolia L., Globularia meridionalis (Podp.) O. Schwarz and Globularia punctata Lapeyr. (Plantaginaceae) is presented. All essential oils contained a variety of oxygenated sesquiterpenes among their major constituents, including a bakkane type sesquiterpene fukinanolid (bakkenolide A). The paper is focused on: i) a short overview of the abundance of major terpenes in the essential oils of Petasites and Globularia species from Croatia; ii) possible biosynthetic pathways of major identified sesquiterpenes; and iii) biological activities (literature data) of major sesquiterpenes from Petasites and Globularia species.

Phytochemical Analysis and Biological Activities of Essential Oils of the Leaves and Flowers of Ageratum houstonianum Mill. Cultivated in Egypt

The essential oils of Ageratum houstonianum Mill grown in Egypt were obtained and studied for the first time. The essential oils of leaves (0.1 % v/w) and flowers (0.06 % v/w) of A. houstonianum Mill. (Asteraceae) were comparatively analyzed by GC/MS using non polar column Rtx-5MS. A total of 11-32 components were identified, 7 being common in both samples. The main constituents of both leaves-and flowers-derived oil samples were precocene I (22.4-34.6 %), β-caryophyllene (63.9-13.7 %), and precocene II (10.8-29.6 %) respectively. The principle difference was a considerably more pronounced sesquiterpenes presence in the leaves-oil, amounting to 65.8 %, than in the flowers counterpart (32.4 %). Caryophyllene (63.9 %) was the major sesquiterpenes detected in leaves-oil, while flowers-oil showed less amounts of sesquiterpenoid hydrocarbons (32.4 %) and represented by caryophyllene (13.5 %). Chromenes was prevailed major constituents of flowers derived oil (64.8 %) nearly double its percent in the leaves derived oil (33.3 %). In vitro screen of antimicrobial and cytotoxic activities was determined against positive control. No antifungal activity was experiential on the tested fungi for all tested samples in the used concentration. Flowers-oil sample is being mostly efficient as antibacterial against Bacillus subtilis and Staphylococcus aureus with potency 50 % compared to gentamicin. The essential oil samples revealed marked in vitro cytotoxicity against colon (HCT-116) carcinoma cell line with IC50 (11.1 %, 14.2 %) μg/ml for the leaves-, flowers-derived oil sample, respectively. The antibacterial effect of the essential oil of the flowers of A.houstonianum Mill can be credited to chromenes. As well as the leaves derived oil prevailed caryophyllene as a major constituents which may justify its observed cytotoxic activity.

Non volatile constituents of the vermouth ingredient Artemisia vallesiaca

The Alpine wormwood Artemisia vallesiaca All. was considered the most valuable ingredient of vermouth, a celebrated aromatized wine. A. vallesiaca has a very limited geographical distribution, and the booming market of vermouth decimated its natural population, resulting in the eventual replacement of this rare species with more common and less expensive wormwoods like A. absinthium L.. Over the past years, attempts to revive the original recipe(s) of vermouth have fostered the establishment of cultivations of A. vallesiaca in pre-montane settings. In order to assist these projects, the phytochemical profile of cultivated plants and of several native populations of A. vallesiaca from the Swiss Valais were comparatively evaluated, focusing on sesquiterpene lactones and on lipophilic flavonoids, the hallmark constituents of Artemisia species. Remarkably, no significant difference was detected between the samples, despite the different origins. The lipophilic flavonoids of A. vallesiaca were similar to those of related species used in the production of vermouth, but the presence of C-9 oxygenated 11β-methyl germacranolides and eudesmanolides (herbolides) made its sesquiterpene lactone profile peculiar. In addition to known compounds, two novel germacranolides were also characterized (herbolides J and K), and the major sesquiterpene lactone from the plant, the bitter germacranolide herbolide D (4), was detected and quantified by 1H NMR in a bitter liqueur aromatized with A. vallesiaca. Taken together, these observations qualify herbolides as marker to identify A. vallesiaca in aromatized alcohol matrixes.

Development and validation of headspace Solid-Phase microextraction coupled with gas chromatography (HS-SPME-GC) method for the analysis of zingiber zerumbet L

Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography (GC-FID) was explored to determine the fingerprinting characteristic of Zingiber zerumbet L. volatiles to differentiate between different ginger species. The effect of different fibers [polydimethylsiloxane (PDMS, 7 μm), polyacrylate (PA, 85 μm)], different temperature and time on the HS-SPME-GC was investigated by using response surface methodology coupled with full factorial experimental design. The area percentage of the major sesquiterpenes (Zerumbone and α-humulene) were 56.3 ± 4.7% and 47.5 ± 27.2% with PA fiber, respectively at optimum condition of 70 °C and 30 min. Validation of the developed HS-SPME-GC method with limits of detection and quantification for zerumbone was 0.09 and 0.28 μg/g, respectively, demonstrating the suitable sensitivity of HS-SPME-GC method for the quantification of sesquiterpenes. Therefore, the simplicity of HS-SPME-GC makes it a convenient tool for qualitative and quantitative comparison of different ginger species targeting at the marker sesquiterpene molecule, zerumbone.

Antitumor activity of alantolactone in lung cancer cell lines NCI-H1299 and Anip973.

Alantolactone is a sesquiterpene lactone extracted from Inula helenium L. plants possessing many biological activities, including anti-inflammatory, antiproliferation, and antimicrobial. The inhibitory effects and the underlying mechanisms of alantolactone on lung cancer cells NCI-H1299 and Anip973 were investigated in this study. The results showed that alantolactone could decrease cell viability and induce cell apoptosis of NCI-H1299 and Anip973. After the cells were treated with alantolactone, the expression of Bcl-2 decreased, while the expression of Bax increased, the expression of MMP-9, MMP-7, and MMP-2 gradually decreased after alantolactone treatment. Furthermore, results showed that alantolactone could activate p38 MAPK pathway and suppress NF-κB pathway, which are involving in lung cancer development. These results indicated that alantolactone was a potential agent for lung cancer treatment. PRACTICAL APPLICATIONS: Lung cancer is one of the most common contributors of cancer death in the world. Chemoprevention and chemotherapy with natural substances are prospective methods for lung cancer treatment. In recent years, the anti-cancer activity of various sesquiterpene lactones has attracted a great deal of interest. Alantolactone is the major active sesquiterpene lactones isolated from Inula helenium L, which is used as a medicine in ancient Romans due to wide range of pharmacological activities. The results obtained from this study revealed the inhibitory effects of alantolactone on lung cancer cells and might provide some experimental basis for prevention and treatment of lung cancer with alantolactone.

β-2-Himachalen-6-ol inhibits 4T1 cells-induced metastatic triple negative breast carcinoma in murine model

β-2-himachalen-6-ol (HC), a major sesquiterpene isolated from the Lebanese wild carrot umbels, was shown to possess remarkable in vitro and in vivo anticancer activities. The present study investigates the anti-metastatic activity of HC post 4T1 breast cancer cells inoculation in a murine model. The effect of HC on 4T1 cell viability was assessed using WST-1 kit, while cell cycle analysis was performed using flow cytometry. Tumor development and metastasis were evaluated by injecting 4T1 cells in the mice mammary gland region followed by either HC or cisplatin treatment. The 6-thioguanine assay was used for the quantification of metastatic cells in the blood. HC treatment caused a dose-dependent decrease in cell viability with IC50 and IC90 values of 7 and 28 μg/mL respectively. Concomitant treatment with cisplatin significantly reduced cell viability when compared to cells treated with cisplatin or HC alone. Flow cytometry revealed a significant increase (p˂0.05) in cell count in the Sub-G1 phase at HC 10 μg/mL, and total DNA fragmentation (p˂0.001) at HC 25 μg/mL. Annexin/PI staining showed early and late apoptotic mode of cell death upon treatment with HC. Histopathological evaluation revealed less incidence of primary and metastatic tumor/inflammation in the HC and cisplatin treated groups. Tumor size and colony-forming units were significantly decreased in the HC treated group. HC treatment induced cell cycle arrest, promoted apoptosis and reduced the incidence of primary and metastatic lesions caused by 4T1 cells. The present findings suggest that HC has an anti-metastatic potential against aggressive types of cancer.

Cloning and characterization of terpene synthase genes from Taiwan cherry

Prunus campanulata Maxim. also known as Taiwan cherry is a broadleaf tree native to Taiwan and is highly valued as an ornamental tree. Terpenoids are one of the most important sources of plant secondary metabolites with many functions such as attracting pollinators, defending against herbivores, and acting as anti-bacterial agents. Here, the terpene synthases (TPSs) that produce small and volatile monoterpenes or sesquiterpenes were focused. Using next-generation sequencing (NGS) technology, we obtained nine full-length cDNAs from P. campanulata which were predicted to encode TPSs. The predicted proteins possessed typical characteristics of TPSs, such as the highly conserved RRX8W and DDXXD motifs. To identify the functions of these TPSs, the recombinant proteins were reacted with the substrate to produce corresponding monoterpenes and sesquiterpenes. Analysis results revealed that the eight TPSs produced their corresponding major monoterpenes and sesquiterpenes, except for one TPS gene that lacks a part of the N-terminus sequence. MeJA treatment (10 mM) resulted in differential expression of these nine TPSs, suggesting that they may have different regulation mechanisms with different functions in plants.

Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis.

Glandular trichomes are specialized anatomical structures that accumulate secretions with important biological roles in plant-environment interactions. These secretions also have commercial uses in the flavor, fragrance, and pharmaceutical industries. The capitate-stalked glandular trichomes of Cannabis sativa (cannabis), situated on the surfaces of the bracts of the female flowers, are the primary site for the biosynthesis and storage of resins rich in cannabinoids and terpenoids. In this study, we profiled nine commercial cannabis strains with purportedly different attributes, such as taste, color, smell, and genetic origin. Glandular trichomes were isolated from each of these strains, and cell type-specific transcriptome data sets were acquired. Cannabinoids and terpenoids were quantified in flower buds. Statistical analyses indicated that these data sets enable the high-resolution differentiation of strains by providing complementary information. Integrative analyses revealed a coexpression network of genes involved in the biosynthesis of both cannabinoids and terpenoids from imported precursors. Terpene synthase genes involved in the biosynthesis of the major monoterpenes and sesquiterpenes routinely assayed by cannabis testing laboratories were identified and functionally evaluated. In addition to cloning variants of previously characterized genes, specifically CsTPS14CT [(-)-limonene synthase] and CsTPS15CT (β-myrcene synthase), we functionally evaluated genes that encode enzymes with activities not previously described in cannabis, namely CsTPS18VF and CsTPS19BL (nerolidol/linalool synthases), CsTPS16CC (germacrene B synthase), and CsTPS20CT (hedycaryol synthase). This study lays the groundwork for developing a better understanding of the complex chemistry and biochemistry underlying resin accumulation across commercial cannabis strains.

Effect of elevated atmospheric carbon dioxide on the allelopathic potential of common ragweed

BackgroundAllelopathy has been suggested as one potential mechanism facilitating the successful colonisation and expansion of invasive plants. The impacts of the ongoing elevation in atmospheric carbon dioxide (CO2) on the production of allelochemicals by invasive species are of great importance because they play a potential role in promoting biological invasion at the global scale. Common ragweed (Ambrosia artemisiifolia var. elatior), one of the most notorious invasive exotic plant species, was used to assess changes in foliar mono- and sesquiterpene production in response to CO2 elevation (389.12 ± 2.55 vs. 802.08 ± 2.69 ppm).ResultsThe plant growth of common ragweed significantly increased in elevated CO2. The major monoterpenes in the essential oil extracted from common ragweed leaves were β-myrcene, dl-limonene and 1,3,6-octatriene, and the major sesquiterpenes were β-caryophyllene and germacrene-D. The concentrations of 1,3,6-octatriene (258%) and β-caryophyllene (421%) significantly increased with CO2 elevation.ConclusionsThese findings improve our understanding of how allelochemicals in common ragweed respond to CO2 elevation.

Alantolactone induces apoptosis through ROS-mediated AKT pathway and inhibition of PINK1-mediated mitophagy in human HepG2 cells

Alantolactone (Ala), a major sesquiterpene lactone extracted from Inula helenium, exerts potent anti-tumour activities in various cancers. However, the underlying mechanism of such activities is still ambiguous. This study focused on evaluating the anti-tumour effects and molecular mechanisms of Ala on HepG2 cells. Our results demonstrated that Ala might inhibit cellular proliferation, induce G2/M phase arrest and apoptosis in HepG2 cells. Specifically, this study confirmed that Ala induced G2/M phase arrest by upregulating p21, downregulating cyclin A1 and cyclin B1, and promoting cellular apoptosis by increasing the expression of cleaved caspase-3 and PARP. Furthermore, Ala caused an increase in reactive oxygen species (ROS) level and inhibition of ROS production significantly prevented Ala-induced apoptosis. Interestingly, the accumulation of ROS, in turn, suppressed the downstream AKT signalling. Finally, mitophagy of Ala-treated HepG2 cells was observed by Mito/Lyso staining. Mitophagy was significantly inhibited by downregulation of the expression of PINK1 and Parkin proteins. The inhibition of mitophagy by a mitophagy inhibitor was found to markedly enhance Ala-mediated apoptosis and growth inhibition in HepG2 cells. Consequently, Ala induced cellular apoptosis via ROS-mediated suppression of AKT signalling and inhibition of PINK1-mediated mitophagy. Thus, Ala has potential to be used for the treatment of liver cancer.

Antiproliferative Effect of Sterols from Resin of Commiphora habessinica

Commiphora habessinica resin is used traditionally to treat various diseases in Ethiopia. In this study the cytotoxic effects of chloroform fraction and cholesterol and lathosterol isolated from the chloroform fraction of the resin of C. habessinica were evaluated. In the cytotoxicity assay on A549, A2780, MIA-Paca-2, and SNU-638 cell lines, the chloroform fraction showed cytotoxicity ranging from 0.77-3.35 ?g/ml. The chloroform fraction significantly inhibited cell proliferation of A549, A2780, MIA-PaCa-2 and SNU-638, with dose-dependent relation in vitro. The chloroform fraction was more sensitive and has a strongest net growth as percent control effects on A549 cell lines. A mixture of cholesterol : lathosterol (47.9% : 52.1%) exhibited a moderate cytotoxicity which is greater than the individual compound towards A549 and A2780 with IC50 of 13.77 and 20.36 ?g/ml, respectively that might be due to synergetic effect. The GC-MS analysis of chloroform fraction of the resin showed presence of pentacyclic triterpenes as major component (62.98%), sesquiterpene (4.27%), phytosterols (1.53%) and others in trace amount. The isolated compounds from the chloroform fraction were analysed by spectroscopic techniques such as NMR and MS.

L‐type Ca2+ channel (Cav1.2) blocking by Z. zerumbet (L., SM) and its major compound sesquiterpene: In vitro, in vivo and in silico approaches

Hypertension is the primary chronic illness around the world. Some drugs available for treating hypertension are ineffective and can present numerous side effects. In this context, medicinal herbs have a long history in the management of hypertension, leading to a reduction in the blood pressure with least side effects. Zingiber zerumbet is a common plant in Northern Brazil, and is usually used for medicinal purposes. The present study aimed to evaluate the biological activity of the essential oil of Z. zerumbet (OEZz) and its main constituent, zerumbone (Zer), on the vascular function of Wistar rats. Vascular reactivity studies together with cell culture assays, histological analysis by stereology and computation molecular docking were performed. Male Wistar rats (220–250 g) from the central animal facility of the Federal University of Amazonas (UFAM) were used in this study. All experiments were carried out in accordance with the Animal Research Ethical Committee of the UFAM (protocol:001/2015). The extraction of the essential oil from the rhizomes of Zingiber zerumbet was carried out by the hydrodistillation method. From the extraction of the oil, Zerumbone undergoes the recrystallization process, giving crystals with a melting point of 65–65.7 °C, density: 0.887 ± 0.06 g/cm 3 and 97% purity. The quantitative and qualitative method of obtaining Zer was patented by our research group (PI 0505343‐9). For the in vivo experiments, the rats received OEZz (50 or 100mg/kg/day) for 21 days. In vitro, OEZz and Zer demonstrated a concentration‐dependent vasodilator effect that were independent of the presence of the endothelium in phenylephrine (10−7M) pre‐constricted vessels, Zer was more potent but with a lower efficacy than OEZz (p <0.05). Pre‐incubation of aortas with OEZz or Zer (103μg/mL) were able to inhibit phenylephrine‐induced vasoconstriction (p <0.0001). OEZz and Zer showed to reduce the potency and efficacy of calcium influx‐mediated vasoconstriction in rings estimulated with phenylephrine (10−7M) or KCl (60mM). OEZz also demonstrated vasodilator potential in vivo, as observed by enlargement of the thoracic aorta. No hypertrophic responses were observed. The molecular docking studies showed that zerumbone may cause a stabilizing or destabilizing influence on the both closed and open states of L‐type Ca 2+ channel by interacting with hydrophobic residues of the P‐loops and inner helices. Additionally, OEZz and Zer demonstrated anti‐inflammatory activity by inhibiting NO production in macrophages, and antioxidant properties by inhibiting the production of ROS. Thus, OEZz and Zer could be potential therapeutic tools for the treatment of cardiovascular disorders, such as hypertension, which is associated with inflammation, oxidative stress and impairment of vascular function.Support or Funding InformationFAPEAM CAPES CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.