Terpenoids from Salvia officinalis and sesquiterpene lactones from Cichorium intybus: anti-trypanosomal efficacy and alleviation of tissue injury in Trypanosoma evansi-infected rats

One of the quality parameters of chicory (Cichorium intybus L.) is its slightly bitter taste which is caused by sesquiterpene lactones. As the quality of chicons is highly dependent on the quality of the roots, the effects of the cultivation conditions of the roots on the levels of sesquiterpene lactones in chicons were investigated. Roots from a collection of 11 commercially available and 2 experimental chicory cultivars were grown at five different locations with two nitrogen manuring levels to evaluate the differences in sesquiterpene lactone levels as measured with enzyme-linked immunosorbent assays (ELISAs). There were significant differences (P<0.001) between cultivars in both lactucopicrin and lactucin-like (lactucin, 8-deoxylactucin and their 11β,13-dihydro derivatives) sesquiterpene lactone levels. In addition, a significant (P=0.006 and P=0.019, respectively) effect of additional nitrogen manuring was observed on the levels of lactucopicrin and lactucin-like sesquiterpene lactones. The interaction of cultivar with nitrogen manuring had a significant (P=0.013) effect on the level of lactucin-like sesquiterpene lactones. Furthermore, the lactucopicrin level was significantly influenced by the interactions of the cultivar with the nitrogen manuring level (P<0.001), with the location (P=0.001) and with both the nitrogen manuring level and location (P<0.001). The results indicate that it may be possible to influence the level of the bitter sesquiterpene lactones and, consequently, to influence the taste of chicons by cultivar choice and/or cultivation location and conditions.

In vitro analysis of the anthelmintic activity of forage chicory (Cichorium intybus L.) sesquiterpene lactones against a predominantly Haemonchus contortus egg population

Background: Cichorium intybus is a perennial herb in the Asteraceae family that has significant ethano-medical properties and is utilized in Ayurveda and Unani therapy. The enzyme costunolide synthase contributes in the biosynthesis pathway of sesquiterpene lactones, which is thought to give the plant antimalarial action. Methods: This work uses several in-silico techniques along with docking experiments to show the structural and physiochemical characteristics of the enzyme costunolide synthase. Costunolide synthase protein interacts with lactucin and lactucopicrin with lower energy interactions of -4.99 kcal/mol for total 3 hydrogen bonds and -6.55 kcal/mol for total 2 hydrogen bonds, respectively. One domain named CYP 450 has been found which catalyzes a variety of oxidative reactions of a large number of structurally different compounds that are both endogenous and exogenous from all major domains of life. The mitochondrial cellular localization of protein was revealed with a maximum score of 1.833. Results: The phylogenetic study revealed that the enzyme costunolide synthase from Cichorium intybus has a greater resemblance to Cichorium endivia and Lactuca sativa of costunolide synthase. Molecular docking findings of sesquiterpene lactones (lactucin and lactucopicrin) with Plasmepsin II protein of P. falciparum parasites after clinical trials with sesquiterpene lactones may give the more evidences and explanations for the active involvement of lactucin and lactucopicrin as an antimalarial compound. Conclusion: This research will be used in future wet lab studies to figure out how the costunolide synthase enzyme regulates sesquiterpene lactones and to investigate additional regulatory enzyme involved in the synthesis of sesquiterpene lactones.

Cichorium intybus L. or chicory plants are a natural source of health-promoting compounds in the form of supplements such as inulin, as well as other bioactive compounds such as sesquiterpene lactones (SLs). After inulin extraction, chicory roots are considered waste, with most SLs not being harnessed. We developed and optimized a new strategy for SL extraction that can contribute to the conversion of chicory root waste into valuable products to be used in human health-promoting applications. In our work, rich fractions of SLs were recovered from chicory roots using supercritical CO2. A response surface methodology was used to optimize the process parameters (pressure, temperature, flow rate, and co-solvent percentage) for the extraction performance. The best operating conditions were achieved at 350 bar, 40 °C, and 10% EtOH as a co-solvent in a 15 g/min flow rate for 120 min. The extraction with supercritical CO2 revealed to be more selective for the SLs than the conventional solid–liquid extraction with ethyl acetate. In our work, 1.68% mass and a 0.09% sesquiterpenes yield extraction were obtained, including the recovery of two sesquiterpene lactones (8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin), which, to the best of our knowledge, are not commercially available. A mixture of the abovementioned compounds were tested at different concentrations for their toxic profile and anti-inflammatory potential towards a human calcineurin/NFAT orthologue pathway in a yeast model, the calcineurin/Crz1 pathway. The SFE extract obtained, rich in SLs, yielded results of inhibition of 61.74 ± 6.87% with 50 µg/mL, and the purified fraction containing 8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin inhibited the activation of the reporter gene up to 53.38 ± 3.9% at 10 µg/mL. The potential activity of the purified fraction was also validated by the ability to inhibit Crz1 nuclear translocation and accumulation. These results reveal a possible exploitable green technology to recover potential anti-inflammatory compounds from chicory roots waste after inulin extraction.

Anthelmintic and metabolomic analyses of chicory (Cichorium intybus) identify an industrial by-product with potent in vitro antinematodal activity

Palatability and anthelmintic activity of chicory (Cichorium intybus L.) forage are influenced by the sesquiterpene lactones lactucin (LAC), 8‐deoxylactucin (DOL) and lactucopicrin. Therefore, the objective of this study was to determine how sesquiterpene lactone concentration and composition vary during the growing season. Three forage chicory cultivars (Puna, Forage Feast and Lacerta) grown in West Virginia and Pennsylvania (USA) were managed during two consecutive years to maintain plants in the vegetative stage, and sesquiterpene lactones in leaves were quantified after each growth interval. Cultivars differed in the total concentration of sesquiterpene lactones and in the proportions of LAC and DOL. Total sesquiterpene lactone concentration generally decreased or remained constant during the season, but the specific response depended on the cultivar. Differences in seasonal patterns between years corresponded with unusual climatic conditions. The three cultivars had similar concentrations of DOL in the spring. Forage Feast provided a dramatically lower concentration of DOL during the summer. Uniformly high concentrations of DOL across the growing season in Puna and Lacerta make these cultivars attractive for use in bioactive pastures for control of Haemonchus contortus. Changes in both sesquiterpene lactone concentration and composition during the season result in large variations in forage bitterness.

Prostate cancer is a condition characterized by the uncontrolled proliferation of abnormal cells inside the prostate gland, part of the male reproductive system. Prostate cancer is the most common cancer among men and the second largest cause of cancer-related mortality in the United States. A novel approach to treating advanced Prostate cancer has emerged, attributable to the enhanced effectiveness of new pharmacological agents sourced from natural origins and this has led to increased rates of global existence and progression-free survival. Sesquiterpene lactones and their derivatives are now used worldwide to create and manufacture innovative cancer therapeutics. A thorough search was performed according to PRISMA guidelines in SciMed, PubMed, and Google Scholar, focusing on publications published from 1999 to 2024. The safety, efficacy, and bioactivity of sesquiterpene lactones must be evaluated via clinical trials, in vitro studies, and in vivo research and data was rigorously gathered and validated to verify its accuracy and usefulness. Prostate cancer may be treated far more effectively using naturally occurring sesquiterpene lactone molecules. The most prominent sesquiterpene lactones identified were artemisinin, alantolactone, costunolide, helenalin, cynaropicrin, parthenolide, and inuviscolide, which are originated from botanical sources like Ferula penninervis, Tanacetum argenteum, Artemisia kopetdaghensis, Cichorium intybus, Carpesium divaricatum, and Leptocarpha rivularis. Numerous studies indicated that sesquiterpene lactones may treat cancer by modifying many cellular signaling pathways, including PI3K/AKT, MAPK, JNK, NF-κB, TNF-α, and STAT3. Sesquiterpene lactones were shown to be significant in suppressing the proliferation of prostate cancer cell lines (DU-145, PC-3, LNCaP, MR49F, and BPH-1) in both laboratory and clinical settings.

The forage potential of chicory (Cichorium intybus L.) has not been realized in southern West Virginia (WV) because ruminants are reluctant to consume the herbage. Chicory contains bitter sesquiterpene lactones that can adversely impact palatability. This study was undertaken to determine whether sesquiterpene lactone concentrations in chicory grown in southern WV differ from those in chicory grown in central Pennsylvania (PA) where chicory is grazed readily. Herbage was collected in 1997 and 1998 from cultivars Grasslands Puna (Puna), INIA le Lacerta (Lacerta), and Forage Feast established at research sites near State College, PA, and Beckley, WV. The total concentration of sesquiterpene lactones in WV-grown cultivars was 0.58% (dry matter basis) in Puna, 0.59% in Lacerta, and 0.79% in Forage Feast in 1997 and ranged from 1.03 (Lacerta) to 1.52% (Forage Feast) in 1998. In PA-grown cultivars, sesquiterpene lactones represented 0.16 (Puna), 0.18 (Lacerta), and 0.27% (Forage Feast) of the forage dry matter in 1997 and ranged from 0.32 (Lacerta) to 0.55% (Forage Feast) in 1998. Concentrations of lactucin, lactucopicrin, and total sesquiterpene lactones in Forage Feast exceeded those in the other cultivars grown at the same site. The lowest concentrations of lactucopicrin and total sesquiterpene lactones observed among WV-grown cultivars were higher (2-fold or more) than the highest concentrations present in cultivars grown the same year in PA. Mineral analyses of soils from the two cultivation sites indicate that P availability may influence sesquiterpene lactone composition of chicory herbage. Results provide a foundation for future studies of environmental effects on sesquiterpene lactone composition and palatability of chicory herbage.

A method for the simultaneous determination of free chlorogenic acids (CGA) and sesquiterpene lactones (STL) in chicory root and its dried (flour) and roasted (grain) forms is described. The method uses one extraction and one analysis for all chicory root products. Various solvents with low to high polarity, such as methanol, chloroform, or n-hexane, were tested alone, in combination in different proportions or with acidified or neutral aqueous solvent. The water/chloroform/methanol (30/30/40, v/v/v) mixture generated the best extraction yield, 21% higher than alcohol mixtures. The profiling of CGA and STL content was performed through a conventional HPLC-DAD method using a PFP core shell column in a fast single run. Good retention time and area repeatability (RDD mean % 0.46 and 5.6, resp.) and linearity (R 2 ≥ 0.96) were obtained. The STL and chlorogenic acids levels determined were 254.7 and 100.2 μg/g of dry matter in the root, 792.5 and 1,547 μg/g in flour, and 160.4 and 822.5 μg/g in the roasted grains, respectively. With an average recovery of 106% and precision of 90%, this method is rapid, reproducible, and straightforward way to quantify the chlorogenic acids and STL in chicory raw material and end products.

ABSTRACTChicory roots produce inulin, a dietary fiber, as well as large quantities of bitter sesquiterpene lactones (STLs), which have valuable biological activities. In an effort to understand the compartmentalization of metabolism within chicory roots and the molecular basis of the development of laticifers that produce the chicory latex, we performed metabolomics and transcriptomics profiling of different tissues of chicory roots. Gas chromatography coupled to mass spectrometry (GC–MS) and liquid chromatography coupled to mass spectrometry (LC–MS) identified a total of 21,437 features, of which 135 were differentially abundant between cell types. Further analysis indicated that the major STLs accumulated primarily in the latex. Gene expression of known STL pathway genes indicates a compartmentalization of the biosynthesis across multiple tissues, with implications regarding the trafficking of pathway intermediates. Phytohormone measurements and gene expression analysis point to a major role for jasmonate signaling in the development and differentiation of laticifers. Furthermore, inulin accumulates mostly outside the laticifers, but expression of inulin metabolic genes also points to a complex distribution and trafficking of inulin or inulin precursors across different root compartments. Altogether, the data presented here constitute a unique resource to investigate several biological processes in chicory roots, including laticifer development, STL biosynthesis and transport, and inulin biosynthesis regulation.

Agronomic factors and quality of vegetable crops

Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2.

Chicory (Cichorium intybus L.) is a commonly used vegetable in Europe and is also regarded as a plant for both medicinal and edible uses in China. Chicory exhibits a substantial abundance of sesquiterpene lactone compounds within its composition. The prevalence of metabolic syndrome (MetS) is increasing and has become a global public health issue threatening the well-being of the general population. Recent studies have identified plant secondary metabolites as potential substances for treating MetS. Sesquiterpene lactones, a type of secondary metabolite with diverse biological activities, have been reported to exhibit anti-inflammatory effects, reduce lipid accumulation, and normalize blood glucose levels. However, the therapeutic effects of chicory sesquiterpene lactones on MetS remain to be explored, and little is known about sesquiterpene lactones' effects on intestinal flora and bile acids (BAs). Therefore, the effects of total sesquiterpene lactones (TSLs) from chicory on metabolic disorders, intestinal flora, and BAs were investigated in this study. In this study, C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, followed by administration of TSLs, total chicory extract (TCE), and pioglitazone (Pio) for another 8 weeks. TSL, TCE, and Pio interventions reduced body weight gain, hepatic lipid accumulation, and lipogenesis in HFD-fed mice and attenuated plasma biochemical parameters. Among them, TSLs exhibited more significant effects, prompting further analysis of their impact on intestinal flora and bile acid metabolism. TSL intervention influenced the composition and structure of intestinal flora and BAs. TSL intervention impacted the composition and structure of the intestinal flora, characterized by a decrease in the abundances of Allobaculum, unidentified_Coriobacteriaceae, and Odoribacter, while the abundances of Prevotella, unidentified_Erysipelotrichaceae and Akkermansia were increased. Additionally, the levels of BAs TCDCA, GDCA, UDCA, 12-ketoLCA, 7-ketoLCA, and 6,7-diketoLCA were reduced. The research results indicated that TSLs from chicory may serve as potential agents for regulating metabolic abnormalities associated with MetS, as their effects can influence intestinal flora and BAs. The conclusions of this study are expected to open new research trajectories in the field of food science and nutrition, providing a solid scientific basis and innovative intervention approaches for the development of strategies targeting MetS prevention and management.

Polyclonal antisera against lactucin and lactucopicrin, two bitter-tasting principles of chicory (Cichorium intybus L.), were obtained after immunization of rabbits with KLH−lactucin and KLH−lactucopicrin conjugates, respectively. In competitive ELISA, the sera from KLH−lactucopicrin-immunized rabbits showed a very low cross-reactivity with other sesquiterpene lactones containing a guaiane skeleton, 0.5% with lactucin, 1% with a mixture of lactucin and 11β,13-dihydrolactucin, and 5% with 8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin. The sera from rabbits immunized with KLH−lactucin showed 50% cross-reaction with 8-deoxylactucin and its 11β,13-dihydro derivative and only 0.4% cross-reaction with lactucopicrin. In competitive ELISAs, chicory extracts spiked with free sesquiterpene lactones showed an expected increase in inhibition level. These ELISAs seem useful in the assessment of chicory bitterness. Keywords: Sesquiterpene lactones; chicory (Cichorium intybus); lactucin; lactucopicrin; bitter taste...

The dissertation aim was to present natural products derived from four common edible medicinal plants that could be applied for solving leishmaniasis, obesity and type 2 diabetes. This research showed leishmanicidal natural compounds isolated from Cichorium intybus L. (Asteraceae), Cornus florida L. (Cornaceae), Eryngium foetidum L. (Apiaceae), which have been used traditionally as antiparasitic remedies. The roots of C. intybus (chicory) yielded four sesquiterpene lactones: (1) 11(S),13-dihydrolactucopicrin, (2) lactucopicrin, (3) 11(S),13-dihydrolactucin and (4) lactucin. Only compound 2 presented leishmanicidal activity (IC 50 24.8 μM). The bark of C. florida (flowering dogwood) afforded eight compounds: (1) betulinic acid, (2) ursolic acid, (3) β-sitosterol, (4) ergosta-4,6,8,22-tetraene-3-one, (5) 3β-O-acetyl betulinic acid, (6) 3- epideoxyflindissol, (7) 3β-O-cis-coumaroyl betulinic acid, (8) 3β-O-trans-coumaroyl betulinic acid. The most active leishmanicidal compounds were (4) 11.5 µM, (6) 1.8 µM, (7) 8.3 µM and (8) 2.2 µM. The aerial parts of E. foetidum (culantro) generated two natural products: (1) lasidiol p-methoxybenzoate and (2) a terpene aldehyde ester derivative. Only compound 1 inhibited L. tarentolae and L. donovani with IC 14.33 and 7.84 μM, respectively. Obesity and type 2 diabetes are reaching alarming levels worldwide. This work presented the anti-inflammatory, anti-obesity and anti-diabetic effect in vitro and in vivo of Moringa oleifera Lam. (Moringaceae), which contains four bioactive isothiocyanates (MICs). Fresh leaves of M. oleifera were extracted with water to obtain a moringa concentrate (MC) containing 1.66% of total MICs. Also, MIC-1 and 4 were isolated from leaves. MC, MIC-1, and MIC-4 significantly decreased gene expression and production of inflammatory markers (NO, TNFα, IL-1β and IL-8) in LPS-stimulated RAW macrophages and Caco2 cells. The MC-treated animals, fed high-fat diet did not gain weight and did not develop fat liver disease compared to control animals. Also, when compared to control animals, the blood metabolic and inflammatory biomarkers from MC-treated mice were in the normal range. In addition MC-treated animals had normal levels of insulin signaling and inflammatory markers in liver, skeletal muscle, white adipose tissue and ileum. MC and MIC inhibited liver gluconeogenesis in vivo as well as in vitro. Finally, an indirect calorimetry acute study indicated that MC-treated mice had a higher fat oxidation rate compared to control mice.