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Ethno-pharmacological relevance Lactucopicrin is one of constitutes in Cichorium intybus L, which is commonly known as chicory in worldwide. It has been used for traditional usage such as antianalgesics, antidepressants and antihyperglycemics Aim of study We investigated the neurotrophin-mediated neuroprotective effect of lactucopicrin in in vitro and examined for the underlying mechanism. Materials and method To verify the neuroprotective effect of lactucopicrin, we investigated the inhibitory AChE activity, neurite outgrowth-related downstream signaling in murine neuroblastoma N2a and neurotrophins secretion in rat C6 glioma cells. Results Lactucopicrin inhibited the AChE activity and increased intracellular Ca 2+ levels with a substantial rise in muscarinic acetylcholine receptor M1 (CHRM1) expression in N2a cells. Moreover, lactucopicrin actively promoted neurite outgrowth via Ca 2+ -mediated activation of Ca 2+ /calmodulin-dependent protein kinase-II (CaMKII). It further activates transcription factor 1 (ATF1) along with modulating the levels of tropomyosin receptor kinase A, extracellular signal-regulated kinase 1 and 2, AKT, and synaptophysin 1 in N2a cells. Additionally, the levels of neurotrophins including NGF, BDNF, and NT3 were increased by treatment of lactucopicrin in C6 cells. The effects of lactucopicrin on NGF secretion and neuritogenesis were maintained even in the presence of phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002, indicating that lactucopicrin exerts its effect on neuritogenesis in a PI3K-independent manner. Conclusion Our results suggest that the natural compound lactucopicrin may be a promising neurotrophin-mediated neuroprotective candidate for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Cholinergic activity plays a vital role in cognitive function, and is reduced in individuals with neurodegenerative diseases. Scopolamine, a muscarinic cholinergic antagonist, has been employed in many studies to understand, identify, and characterize therapeutic targets for Alzheimer’s disease (AD). Scopolamine-induced dementia is associated with impairments in memory and cognitive function, as seen in patients with AD. The current study aimed to investigate the molecular mechanisms underlying scopolamine-induced cholinergic neuronal dysfunction and the neuroprotective effect of lactucopicrin, an inhibitor of acetylcholine esterase (AChE). We investigated apoptotic cell death, caspase activation, generation of reactive oxygen species (ROS), mitochondrial dysfunction, and the expression levels of anti- and pro-apoptotic proteins in scopolamine-treated C6 cells. We also analyzed the expression levels of antioxidant enzymes and nuclear factor (erythroid-derived 2)-like 2 (NRF2) in C6 cells and neurite outgrowth in N2a neuroblastoma cells. Our results revealed that 1 h scopolamine pre-treatment induced cytotoxicity by increasing apoptotic cell death via oxidative stress-mediated caspase 3 activation and mitochondrial dysfunction. Scopolamine also downregulated the expression the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase, and the transcription factor NRF2. Lactucopicrin treatment protected C6 cells from scopolamine-induced toxicity by reversing the effects of scopolamine on those markers of toxicity. In addition, scopolamine attenuated the secretion of neurotrophic nerve growth factor (NGF) in C6 cells and neurite outgrowth in N2a cells. As expected, lactucopicrin treatment enhanced NGF secretion and neurite outgrowth. Our study is the first to show that lactucopicrin, a potential neuroprotective agent, ameliorates scopolamine-induced cholinergic dysfunction via NRF2 activation and subsequent expression of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Abstract: The effect of nutrient solution electrical conductivity (EC) and sulfur (S), magnesium (Mg), and phosphorus (P) levels on the content of the primary sesquiterpene lactones (SLs), lactucin, 8-deoxylactucin, and lactucopicrin, in hydroponically grown lettuce was assessed. Lettuce grown at 4 EC levels (0.5, 1.0, 2.0, and 3.0dSm−1) displayed significant differences in leaf area index, number of leaves, plant height, fresh weight per plant, and chlorophyll content that were highest at EC 2.0dSm−1. Lactucin (5.5μgg−1 dry weight), 8-deoxylactucin (7.5), lactucopicrin (35.8), and total SLs (48.7) concentraions were highest at EC 0.5dSm−1. Four S (8, 16, 48, and 80mgL−1) and Mg (6, 12, 36, and 60mgL−1) levels and 3 P (8, 16, and 48mgL−1) levels were assessed for their effect on individual and total SLs. S and P had the greatest effect on SL levels. Plants in the lowest S level had significantly higher lactucin, lactucopicrin and total SLs. Each of the SLs was higher in the highest P level while Mg influenced only the lactucopicrin level in a quadratic manner. The results indicate that solution culture conditions can strongly influence the SL concentration and therefore bitterness and acceptability of lettuce. [Copyright &y& Elsevier]

Abstract: Because of the skeletal complexity and similarity of the polarity, little research was reported on the isolation of sesquiterpene lactones by high-speed counter-current chromatography (HSCCC). Herein, three sesquiterpene lactones were successfully purified from the ethyl acetate extract of the roots of the traditional Uyghur medicinal plant Cichorium glandulosum Boiss. et Huet. by HSCCC. The separation was performed in two steps with two solvent systems: n-hexane–ethyl acetate–methanol–water (1.5:5:2.75:5, v/v/v/v) and ethyl acetate–methanol–water (20:1:20, v/v/v). From 166mg of the ethyl acetate extract, 19mg of lactucopicrin was isolated with the first solvent system and 10mg of 11β,13-dihydrolactucin and 16mg of lactucin were obtained with the second solvent system. All purified compounds were over 94% purity as determined by HPLC analysis, and these chemical structures were confirmed by 1H NMR and 13C NMR. [Copyright &y& Elsevier]

[Display omitted] Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucopicrin could inhibit vascular endothelial nuclear factor-κB (NF-κB) activation, a hallmark of vascular inflammatory diseases including sepsis. In tumor necrosis factor-α-stimulated human or mouse aortic endothelial cells, lactucopicrin dose-dependently inhibited NF-κB activation, and concomitantly repressed both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)-mediated monocyte adhesion. The lactucopicrin effect was not due to modulation of inhibitor of NF-κB kinases (IKK) α/β/γ, inhibitor of NF-κB alpha (IκBα), and NF-κB/p65 DNA binding activity. Instead, lactucopicrin inhibited importin-α3 expression by destabilization of its mRNA, an effect mediating the lactucopicrin effect on NF-κB activity. More importantly, in lipopolysaccharide (LPS)-elicited septic mice, oral gavage with lactucopicrin decreased mortality by 30.5% as compared with the control treatment. This effect was associated with inhibited importin-α3 expression, suppressed NF-κB activation and VCAM-1/ICAM-1 expression, and inhibited leukocyte influx in the vascular endothelium of both lung and aorta. Collectively, our novel data suggest that dietary supplementation with lactucopicrin inhibits endothelial NF-κB activation by down-regulation of importin-α3 and thereby improves sepsis. [ABSTRACT FROM AUTHOR]

• Crowding surrounding was suggested for preparation of MIP using template molecule with low purity. • Crowding surrounding was made up of high molecular PS. • The necessity of simultaneous use of PS was proved to prepare MIP with impure template. • The MIP made can be used in SPE to purify lactucopicrin from the crude extract. The topic in the present paper is to prepare molecularly imprinted polymer (MIP) using the template molecule with low purity. For the first time, a surrounding of macromolecular crowding was established to promote the formation of the complex of the template with functional monomer efficiently thus highly pure template molecule was unnecessary. In this study, the MIP monolith was synthesized using low purity lactucopicrin as template in place of highly pure one, and polystyrene was used as macromolecular crowding agent. 4-Vinylpyridine and ethyleneglycol dimethacrylate were used as functional monomer and crosslinker, respectively. Polymerization parameters, including the ratio of functional monomer/template, various template concentrations, and PS concentration on the affinity of the resulting MIP were systematically investigated. For the lactucopicrin MIP made with the purity of lactucopicrin of 92%, the imprinting factor can be up to 2.2. The resulting MIP was filled in solid phase extraction (SPE) cartridge to purify lactucopicrin from the crude extract of Cichorium glandulosum Boiss. et Huet. After two cycles of MIP SPE for the crude extract, the highest recovery and purity of lactucopicrin was 64.8% and 97.8%, respectively. The results indicated that the use of macromolecular crowding agent is an effective method for improving the performance of the MIP prepared with the template of low purity, particularly valuable to the cases in which the highly pure target molecule is hard to be obtained. [ABSTRACT FROM AUTHOR]

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, 11 β ,13-dihydrolactucin, crepidiaside B, 8-deoxylactucin, jacquinelin, lactucopicrin/11 β ,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/11 β ,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. • Eight guaianolides and one germacranolide were profiled in extracts from Lactuca altaica • Mainly quantitative differences were observed among the individual accessions • Typical of L. altaica plants was high content of lactuside A in the roots • The plants contained relatively high amounts of lactucopicrin/dihydrolactucopicrin • Sesquiterpene lactones were more abundant in roots than in the leaves of L. altaica [ABSTRACT FROM AUTHOR]

Abstract: Folklore reports from Afghanistan prior to the wars described the use of aqueous root extracts of Cichorium intybus (L.) as a light-sensitive plant remedy for malaria. Preparative isolation and bioassay against HB3 clone of strain Honduras-1 of Plasmodium falciparum identified the previously known light-sensitive sesquiterpene lactones Lactucin and Lactucopicrin to be antimalarial compounds. [Copyright &y& Elsevier]