Sesquiterpene Lactones Costunolide Research Articles

Laurus azorica: Valorization through Its Phytochemical Study and Biological Activities

Laurus azorica (Seub.) Franco is an endemic species from the Azores, traditionally used in all the islands as a seasoning in cooking. The studies carried out with this species refer mainly to its essential oils. The study that was developed here allowed, for the first time, to determine the chemical composition and biological activities of the ethanol extract, fractions, and pure compounds from L. azorica. The hexane fraction was analyzed by GC–MS and revealed the presence of 48 compounds, comprising mainly fatty acids, fatty alcohols and terpenes, the family of fatty alcohols identified here for the first time in the genus Laurus. Three sesquiterpene lactones—costunolide, 11,13-dehydrosantonin and reynosin—were isolated for the first time in L. azorica from the same fraction, and structurally characterized using spectroscopic techniques. The compounds identified belong to families known to have relevant medicinal and nutritional properties. Regarding antioxidant activities, the results obtained showed a moderate radical scavenging effect of extracts and fractions, while in the β-carotene bleaching assay, costunolide was shown to be the most active (IC50 = 4.08 ± 0.76 μg/mL), about 3.6 times more active than the standard, gallic acid, which presented IC50 = 14.56 ± 0.13 μg/mL. Although the inhibition of extracellular matrix-degrading enzymes was not detected, the ethanol extract showed good inhibitory activity of tyrosinase, with an IC50 of 12.04 ± 0.23 μg/mL, only 6.6-fold lower than the control kojic acid. The results presented deepen the knowledge about a little studied species, opening new perspectives for the development of value-added applications in the food and cosmeceutical fields.

Phytotoxicity Study on Bidens sulphurea Sch. Bip. as a Preliminary Approach for Weed Control.

Farmers of the Franca region in Brazil observed that Bidens sulphurea was able to eliminate the Panicum maximum weed, which infected coffee plantations, without affecting the crop. In an effort to determine if the inhibitory effects observed were due to the presence of phytotoxic compounds from leaves and roots, a biodirected isolation and spectroscopic characterization has been carried out. The leaf dichloromethane and root acetone extracts were the most active, and the former appeared to be more phytotoxic to the target species, including four weeds. A total of 26 compounds were isolated from leaves and roots, and four of them are described here for the first time. The major compounds in the leaf extract are the sesquiterpene lactones costunolide, reynosin, and santamarine, and these showed marked inhibition. Amaranthus viridis and Panicum maximum were the most sensitive species of the weeds tested. These three phytotoxic lactones were also evaluated on A. viridis and P. maximum under hydroponic conditions. A. viridis was the most affected species with the three lactones, and santamarine was the most phytotoxic compound on both. This is the first time that the phytotoxicity of sesquiterpene lactones has been evaluated on hydroponic culture. The work described here is a preliminary approach for the use of B. sulphurea for weed control in agriculture, both as a cover crop and by use of its components as natural herbicide leads.

Anti-allergic effects of sesquiterpene lactones from the root of Aucklandia lappa Decne

Aucklandia lappa Decne, a well-known traditional herbal medicine, is used for the treatment of asthma, rheumatism, coughs, tuberculosis and numerous other diseases. The present study evaluated the inhibitory effects of the three sesquiterpene lactones costunolide, dehydrocostus lactone, and alantolactone, isolated from a 70% methanolic extract of Aucklandia lappa, on the expression of chemokine mRNA in HaCaT human keratinocyte cells. The cytotoxicities of the compounds on HaCaT cells were evaluated using a Cell Counting Kit8 assay. Furthermore, the inhibitory effects of the three compounds on chemokine expression in tumor necrosis factor (TNF)‑α‑ and interferon (IFN)‑γ‑stimulated HaCaT cells were analyzed by reverse transcription-polymerase chain reaction analysis. Treatment with the compounds caused a significant reduction in the mRNA expression of a range of chemokines, including TARC/CCL17, MDC/CCL22, RANTES/CCL5 and interleukin‑8 in TNF-α and IFN-γ-stimulated HaCaT cells. The present study indicated that costunolide, dehydrocostus lactone and alantolactone may have the potential to be used for treating inflammatory skin disorders by suppressing chemokine expression.

Pharmacokinetics study on costunolide and dehydrocostuslactone after administration of traditional Chinese medicine Weichang'an pills

A HPLC-MS/MS multiple-reaction monitoring (MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide (Co) and dehydrocostuslactone (De) in blood samples in the positive ion mode, with diazepam as the internal standard substance, in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang'an pills, and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples, Co and De showed a good linearity within concentration ranges 0.700 0-769.7, 2.510-956.0 μg x L(-1), respectively. The results of precision, stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration, the concentrations of Co and De in plasma increased with the increase in dose, with T(max) between 10.65-12.98 h, indicating a long time to reach peak plasma concentrations; C(max) of costunolide and dehydrocostuslactone ranged between 3.750-5.450,15.34-44.52 μg x L(-1), respectively. The in vivo adsorption of Co and De conformed to the one-compartment model, with a longer time to attain the peak plasma concentrations. These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.

Sesquiterpene Lactones Downregulate G2/M Cell Cycle Regulator Proteins and Affect the Invasive Potential of Human Soft Tissue Sarcoma Cells

Soft tissue sarcomas (STS) represent a rare group of malignant tumors that frequently exhibit chemotherapeutic resistance and increased metastatic potential. Many studies have demonstrated the great potential of plant-derived agents in the treatment of various malignant entities. The present study investigates the effects of the sesquiterpene lactones costunolide and dehydrocostus lactone on cell cycle, MMP expression, and invasive potential of three human STS cell lines of various origins. Both compounds reduced cell proliferation in a time- and dose-dependent manner. Dehydrocostus lactone significantly inhibited cell proliferation, arrested the cells at the G2/M interface and caused a decrease in the expression of the cyclin-dependent kinase CDK2 and the cyclin-dependent kinase inhibitor p27Kip1. In addition, accumulation of cells at the G2/M phase transition interface resulted in a significant decrease in cdc2 (CDK1) together with cyclin B1. Costunolide had no effect on the cell cycle. Based on the fact that STS tend to form daughter cell nests and metastasize, the expression levels of matrix metalloproteinases (MMPs), which play a crucial role in extracellular matrix degradation and metastasis, were investigated by Luminex® technology and real-time RT-PCR. In the presence of costunolide, MMP-2 and -9 levels were significantly increased in SW-982 and TE-671 cells. Dehydrocostus lactone treatment significantly reduced MMP-2 and -9 expression in TE-671 cells, but increased MMP-9 level in SW-982 cells. In addition, the invasion potential was significantly reduced after treatment with both sesquiterpene lactones as investigated by the HTS FluoroBlock™ insert system.

Sesquiterpene lactones with potential use as natural herbicide models (I): trans,trans-germacranolides.

A structure-activity study to evaluate the effect of the trans, trans-germacranolide sesquiterpene lactones costunolide, parthenolide, and their 1,10-epoxy and 11,13-dihydro derivatives (in a range of 100-0.001 microM) on the growth and germination of several mono and dicotyledon target species is accomplished. Results are compared with those obtained in the same bioassay with an internal standard, the commercial herbicide Logran, to validate the results with a known active formulation and to compare the results with a commercial product to test their potential use as natural herbicide models. These compounds appear to have a more selective effects on the radicle growth of monocotyledons. Certain factors such as the presence of nucleophile-acceptor groups and their accessibility enhance the inhibitory activity. The levels of radicle inhibition obtained with some compounds on wheat are totally comparable to those of Logran and allow to propose them as lead compounds.

Sesquiterpenes from southern Magnolia virginiana

A chemical study of the leaves of the southern evergreen Magnolia virginiana provided, besides the known sesquiterpene lactones costunolide, parthenolide and trifloculoside, two new sesquiterpenes, costunolact-12β-ol and its acetal dimer. The molecular structure of the acetal dimer of costunolact-12β-ol was determined by single crystal X-ray diffraction. An annual study of the relative ratios of the major sesquiterpenes in leaves of M. virginiana showed < 10% of costunolide over the 12 month period. In contrast, parthenolide and costunolact-12β-ol varied markedly over the same time period with a maximum of > 90% of parthenolide in July/August and a minimum of < 20% in January. However, no lignans typical of the northern variety of M. virginiana could be detected in the annual study of the southern variety of this taxon.

Isolation and Characterization of the Sesquiterpene Lactones Costunolide, Parthenolide, Costunolide Diepoxide, Santamarine, and Reynosin from Magnolia grandiflora L.

The germacranolide sesquiterpene lactones costunolide, parthenolide, and costunolide diepoxide were isolated from the leaves of Magnolia grandiflora L. Costunolide diepoxide might be, at least in part, an artifact derived from air oxidation of parthenolide. The root bark yielded only costunolide together with the two eudesmanolides, santamarine and reynosin. In an attempt to synthesize costunolide diepoxide, the action of m-chloroperbenzoic acid on parthenolide and on costunolide was studied. The products were costunohde diepoxide from parthenolide and the two cyclized derivatives, santamarine and reynosin, from costunolide. The elusive costunolide 1,10-epoxide was obtained by epoxidizing costunolide using a biphasic system containing sodium bicarbonate. Under these conditions, epoxidation of costunolide took place without cyclization.

Simultaneous application of the nuclear Overhauser effect and an N.M.R. shift reagent. Conformation of costunolide and dihydrocostunolide in solution

Conformations of the ten-membered ring sesquiterpene lactones costunolide (1) and dihydrocostunolide (2) in [2H]chloroform have been determined by intramolecular inter-nuclear Overhauser effect measurements in the presence of an n.m.r. lanthanide shift reagent, [2H27]Eu(fod)3; care must be taken in applying these techniques simultaneously.