Antimalarial activity of Lactucin and Lactucopicrin: Sesquiterpene lactones isolated from Cichorium intybus L.

Department of Pharmacy, Massachusetts General Hospital, Boston, MA 02114, USA.
Journal of Ethnopharmacology (Impact Factor: 3). 01/2005; 95(2-3):455-7. DOI: 10.1016/j.jep.2004.06.031
Source: PubMed


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.

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    • "Sesquiterpene lactones are PSM thought to be involved in the protection of plants against herbivore attacks and for signalling between plants (Gershenzon and Dudareva, 2007). In biological systems, SL have demonstrated antioxidant, antibiotic, anticancerigenous and antiprotozoan properties (Bischoff et al., 2004; Cavin et al., 2005; Schmidt, 2006; Barrera et al., 2013). "
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    ABSTRACT: The study investigated direct anthelmintic effects of sesquiterpene lactones (SL)-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars ‘Spadona’ and ‘Puna II’ were extracted using methanol/water. Total SL were further fractionated by solid-phase extraction and resulting extracts were characterised by high-performance liquid chromatography (HPLC). O. ostertagi eggs from faeces of mono-infected calves were hatched and L1 were used in a larval feeding inhibition assay (LFIA), while cultured L3 were used in a larval exsheathment inhibition assay (LEIA). Adult worms were immediately recovered after slaughter and used for motility inhibition assays (AMIA). Electron microscopy (EM) was performed on adult O. ostertagi exposed to 1000 μg extract mL-1 of both chicory cultivars. In all assays, decreasing concentrations of SL-containing extracts in PBS (1% DMSO) were tested in replicates with 1% DMSO in PBS as negative controls. HPLC demonstrated similar concentrations of most SL in both extracts. However, Spadona-extract contained significantly higher concentrations of 11, 13-dihydro-8-deoxylactucin (P=0.01), while Puna II-extract had increased levels of 11, 13-dihydrolactucin (P<0.0001). In the LFIA, both extracts reduced larval feeding at increasing concentrations, but Spadona-extract showed higher potency confirmed by significantly lower EC50 (P<0.0001). In the LEIA, neither of the two extracts interfered with the exsheathment of L3 (P>0.05). In the AMIA, both SL-containing extracts induced a dose-dependent effect but Spadona-extract showed greater activity and exerted faster worm paralysis than Puna II-extract with significantly lower EC50 (P<0.0001). No cuticular damage was observed by EM in worms exposed to any of the extracts. We have demonstrated that SL-containing extracts from forage chicory can inhibit feeding of free-living larvae and exert direct effects against parasitic stages of O. ostertagi. Our results may contribute to the identification of natural anti-parasitic compounds and to interpret the in vivo anthelmintic effects of forage chicory.
    International Journal for Parasitology: Drugs and Drug Resistance 10/2015; DOI:10.1016/j.ijpddr.2015.10.002 · 3.29 Impact Factor
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    • "Chicory leaves, and especially roots, are rich in lactucin-like guaianolides: lactucin, its p-hydroxyphenylacetic acid ester lactupicrin (or lactucopicrin), 8- deoxylactucin, as well as their 11(S),13-dihydroderivatives and glycosides, while the levels of eudesmanolides and germacranolides are lower (Kisiel and Zielinska, 2001; Malarz et al., 2002; Van Beek et al., 1990). Guaianolides are shown to have antifeedant (Rees and Harborne, 1985), antifungal (Barrero et al., 2000), antiprotozoal and cytotoxic activity, as well as potent antimalarial effect (Bischoff et al., 2004). "
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    ABSTRACT: Chicory (Cichorium intybus L) is rich in bitter sesquiterpene lactones, mainly guaianolides: lactucin, 8-deoxylactucin, lactupicrin and their 11(S),13-dihydroderivatives-compounds recognized for their antimicrobial and anti-cancer effects. In vitro plant tissue culture, and particularly Agro bacterium rhizogeries-generated hairy root (HR) cultures, have many advantages as systems for production of valuable secondary metabolites. Although chicory HRs grow better than control culture, having nearly 60 times greater fresh weight gain, they do not contain a higher content of guaianolides than wild type (wt) roots. Thus we have established in vitro system comprised of wt root and HR cultures, and wt and transformed regenerated plants of the same age, in rosette and flowering stage, in order to study the effects of transformation, organogenesis and flowering on guaianolides production. Both regeneration and flowering in vitro were spontaneous, so the results were not influenced by exogenous growth regulators. Some of the transformed clones grew better, but all flowered earlier in comparison to wt plants. Floral transition increased guaianolides content in both roots and leaves of transformed, but not of wt plants. Expression of RolC oncogene correlated with floral transition and with guaianolides accumulation. We propose A. rhizogenes transformed plants at the flowering stage as an alternative source of free guaianolides, where, in contrast to HRs, entire plants can be used for the extraction.
    Industrial Crops and Products 09/2014; 60:52–59. DOI:10.1016/j.indcrop.2014.05.054 · 2.84 Impact Factor
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    • "al., 2007a, 2007b), and flavonoids (Yang et al., 2009), extensive studies in recent years have displayed that Cichorium has various kinds of bioactivities including photo protective (Enk et al., 2004, Heimlera Daniela et. al., 2009), hepatoprotective (Upur et al., 2009, Hanaa and Mokhtar, 2010), antimalarial (Bischoff et al., 2004) anti-inflammatory (Cavin et al., 2005), antitumor (Hazra et al., 2002, Al-Akhras MA et al., 2012) antiviral (Matvieieva et al., 2012), antioxidative (Lavelli, 2008), anti-diabetic (Xin et al., 2012, Yao et al., 2013, Muthusamy et al., 2008) and cholesterol-lowering (Zhao et al., 2012, Kim et al., 2008) effects. "
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    ABSTRACT: Ethnopharmacological relevance: Cichorum glandulosum Boiss. et Huet is a traditional Uygur herbal medicine that has been used as a cholagogic and diuretic agent to improve liver function. However, the mechanism is not known for the liver-protective function. We investigated the antioxidant effects of plant extraction (CGE60) in vitro and in vivo, and find the mechanism of liver protection in Bacille Calmette-Guerin vaccine (BCG)+Lipopolysaccharides (LPS) induced liver injury in mice. Materials and methods: CGE60 was made, and the antioxidant activity was investigated by comparing the ability of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2-azinobis(3-ehtylbenzothiazolin-6-sulfnicAcid) diammonium salt (ABTS) free radicals in vitro. Then, CGE60 was administrated in mice of liver damage model which was induced in mice using the BCG+LPS protocol. The CGE 60 extract was tested at three dosages: 50 mg/kg, 100 mg/kg, and 200 mg/kg. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX,), nitric oxide (NO), nitric oxide synthetase (NOS), hydroxyproline and alkaline phosphatase (ALP) contents were evaluated in liver to determine the CGE60 activity in the hepatic injury model. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) proteins were determined in the liver tissues using ELSIA. The signaling activities were evaluated in Western blot. Results: CGE60 exhibited strong antioxidant ability in vitro. With oral administration, CGE60 significantly increased the activity of CAT, SOD, GSH-PX, and decreased the level of NO, NO synthase, hydroxyproline, ALP and lipid peroxidation liver of in the BDG+ LPS model. CGE60 attenuated hepatic inflammation via down- regulation of TNF-α, IL-6 and TGF-β. CGE60 blocked protein expression of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa-B (NF-κB), phosphorylation of extracellular signal-regulated kinase (p-ERK1/2), and cyclooxygenase-2 (COX-2),but activated the expression of p-P38 MAPK. Conclusion: This study suggests that CGE60 possesses antioxidant activity and this activity associates with hepatoprotective effect in the mice of BCG +LPS model, and the mechanisms underlying these effects may involve antioxidant actions and anti-inflammation activities.
    Journal of Ethnopharmacology 06/2014; 155(2). DOI:10.1016/j.jep.2014.06.014 · 3.00 Impact Factor
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