Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Food Funct. 2024 Sep 16;15(18):9254-9271. doi: 10.1039/d4fo01446d.

Unveiling the anti-inflammatory potential of 11β,13-dihydrolactucin for 
application in inflammatory bowel disease management.

Matos MS(1)(2), Ávila-Gálvez MÁ(1)(3), González-Sarrías A(4), Silva NV(3), 
Crespo CL(3), Jacinto A(3)(5), Serra AT(1)(2), Matias AA(1), Nunes Dos Santos 
C(1)(2)(3)(5).

Author information:
(1)Instituto de Biologia Experimental e Tecnológica (iBET), 2780-157 Oeiras, 
Portugal. claudia.nunes.santos@nms.unl.pt.
(2)Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova 
de Lisboa (ITQB-NOVA), 2780-157 Oeiras, Portugal.
(3)NOVA Medical School, Faculdade de Ciências Médicas, NMS|FCM, Universidade 
Nova de Lisboa, 1169-056 Lisboa, Portugal.
(4)Laboratory of Food & Health, Research Group on Quality, Safety and 
Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, 
Spain.
(5)NOVA Institute for Medical Systems Biology, NIMSB, Universidade Nova de 
Lisboa, 1099-085 Lisboa, Portugal.

Management of inflammatory bowel disease (IBD) poses significant challenges, and 
there is a need for innovative therapeutic approaches. This study investigates 
the anti-inflammatory properties of the dietary sesquiterpene lactone (SL) 
11β,13-dihydrolactucin, which can be found in chicory, in three distinct 
complementary models of intestinal inflammation (two cell models and a zebrafish 
model), offering comprehensive insights into its potential application for IBD 
treatment alternatives. In a triple cell co-culture composed of Caco-2, 
HT29-MTX-E12, and Raji B, 11β,13-dihydrolactucin demonstrated remarkable 
anti-inflammatory activity at several levels of the cellular inflammatory 
response. Notably, 11β,13-dihydrolactucin prevented the activation of critical 
signalling pathways associated with inflammation, namely NF-κB and MAPK p38. 
This SL also decreased the release of the neutrophil-recruiting chemokine IL-8. 
Additionally, the compound reduced the gene expression of IL-6 and TNF-α, as 
well as the gene and protein expression of the inflammatory inducible enzymes 
iNOS and COX-2. In a myofibroblast-like human cell model, 11β,13-dihydrolactucin 
decreased the release of the cytokine TNF-α and the COX-2-derived inflammation 
mediator PGE2. Finally, in a zebrafish model of gut inflammation, 
11β,13-dihydrolactucin effectively reduced neutrophil infiltration, further 
supporting its anti-inflammatory efficacy in a physiological context. 
Collectively, our findings highlight the promising anti-inflammatory potential 
of 11β,13-dihydrolactucin across various facets of intestinal inflammation, 
providing a foundation for the consideration of chicory as a promising candidate 
for incorporation in food or nutraceutical products for the potential prevention 
of IBD.

DOI: 10.1039/d4fo01446d
PMID: 39162124 [Indexed for MEDLINE]


2. Chembiochem. 2024 Mar 15;25(6):e202300722. doi: 10.1002/cbic.202300722. Epub 
2024 Feb 21.

Biocatalytic Regioselective O-acylation of Sesquiterpene Lactones from Chicory: 
A Pathway to Novel Ester Derivatives.

Mosheim JR(1), Ruggieri F(1)(2), Humeau C(3), Hance P(1)(4), Willand N(2), 
Hilbert JL(1)(4), Heuson E(5), Froidevaux R(1).

Author information:
(1)Univ. Lille, INRA, ISA, Univ. Artois, Univ. Littoral Côte d'Opale, EA 7394 - 
Institut Charles Viollette, Lille, France.
(2)Univ. Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for 
Living Systems, F-59000, Lille, France.
(3)Univ. Lorraine, CNRS, UMR 7274 - Laboratoire Réactions et Génie des Procédés, 
-, F-54000, Nancy, France.
(4)Joint Laboratory University of Lille-Florimond-Desprez CHIC41Health, F-59655, 
Villeuneve d'Ascq, France.
(5)Univ. Lille, CNRS, Centrale Lille, Univ. Artois, UMR 8181-UCCS-, Unité de 
Catalyse et Chimie du Solide, F-59000, Lille, France.

We report the first biocatalytic modification of sesquiterpene lactones (STLs) 
found in the chicory plants, specifically lactucin (Lc), 11β,13-dihydrolactucin 
(DHLc), lactucopicrin (Lp), and 11β,13-dihydrolactucopicrin (DHLp). The 
selective O-acylation of their primary alcohol group was carried out by the 
lipase B from Candida antarctica (CAL-B) using various aliphatic vinyl esters as 
acyl donors. Perillyl alcohol, a simpler monoterpenoid, served as a model to set 
up the desired O-acetylation reaction by comparing the use of acetic acid and 
vinyl acetate as acyl donors. Similar conditions were then applied to DHLc, 
where five novel ester chains were selectively introduced onto the primary 
alcohol group, with conversions going from >99 % (acetate and propionate) to 
69 % (octanoate). The synthesis of the corresponding O-acetyl esters of Lc, Lp, 
and DHLp was also successfully achieved with near-quantitative conversion. 
Molecular docking simulations were then performed to elucidate the preferred 
enzyme-substrate binding modes in the acylation reactions with STLs, as well as 
to understand their interactions with crucial amino acid residues at the active 
site. Our methodology enables the selective O-acylation of the primary alcohol 
group in four different STLs, offering possibilities for synthesizing novel 
derivatives with significant potential applications in pharmaceuticals or as 
biocontrol agents.

© 2024 Wiley-VCH GmbH.

DOI: 10.1002/cbic.202300722
PMID: 38235523 [Indexed for MEDLINE]


3. Biomed Pharmacother. 2023 Nov;167:115413. doi: 10.1016/j.biopha.2023.115413. 
Epub 2023 Sep 8.

Costunolide and parthenolide: Novel blood-brain barrier permeable sesquiterpene 
lactones to improve barrier tightness.

Ávila-Gálvez MÁ(1), Marques D(2), Figueira I(2), Cankar K(3), Bosch D(3), Brito 
MA(4), Dos Santos CN(5).

Author information:
(1)Instituto de Biologia Experimental e Tecnológica (iBET), Av. República, Qta. 
Marquês, 2780-157 Oeiras, Portugal; iNOVA4Health, NOVA Medical School|Faculdade 
de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Lisboa, Portugal.
(2)iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, 
Universidade Nova de Lisboa, Lisboa, Portugal.
(3)Wageningen University and Research, Wageningen Plant Research, BU Bioscience, 
Droevendaalsesteeg 1, 6708PB Wageningen, the Netherlands.
(4)Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; 
Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, 
Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
(5)Instituto de Biologia Experimental e Tecnológica (iBET), Av. República, Qta. 
Marquês, 2780-157 Oeiras, Portugal; iNOVA4Health, NOVA Medical School|Faculdade 
de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Lisboa, Portugal. 
Electronic address: claudia.nunes.santos@nms.unl.pt.

Sesquiterpene lactones - such as those found in chicory - are considered 
promising bioactive compounds. These small molecules have shown several health 
benefits for various diseases, including brain disorders. However, it is unknown 
whether these compounds can cross the blood-brain barrier (BBB), and which could 
be the effects on brain microvascular endothelial cells. We show that six 
sesquiterpene lactones evaluated in an in vitro model of the BBB have different 
capacities to be transported through the barrier. Costunolide presented more 
than 20 % of transport while lactucin, 11β-13-dihydrolactucin, 
11β-13-dihydrolactucopicrin, and parthenolide presented between 10 % and 20 %, 
whilst almost no transport was detected for lactucopicrin. Furthermore, 
costunolide and parthenolide reduced P-gp ABC transporter expression alongside 
an increase in caveolin-1, the main protein of caveolae. Remarkably, these two 
compounds improved barrier tightness by increasing the expression of both tight 
and adherens junctions. These findings open a new avenue to explore costunolide 
and parthenolide as promising compounds for brain therapies.

Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights 
reserved.

DOI: 10.1016/j.biopha.2023.115413
PMID: 37683593 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


4. Pharmaceuticals (Basel). 2023 May 22;16(5):771. doi: 10.3390/ph16050771.

A Three-Step Process to Isolate Large Quantities of Bioactive Sesquiterpene 
Lactones from Cichorium intybus L. Roots and Semisynthesis of Chicory STLs 
Standards.

Ruggieri F(1), Hance P(2)(3), Gioia B(1), Biela A(1), Roussel P(4), Hilbert 
JL(2), Willand N(1).

Author information:
(1)Univ. Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for 
Living Systems, F-59000 Lille, France.
(2)UMRT 1158 BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, Univ. Picardie 
Jules-Verne, YNCREA, Univ. Artois, Univ. Littoral Côte d'Opale, ICV-Institut 
Charles Viollette, F-59000 Lille, France.
(3)Joint Laboratory University of Lille-Florimond-Desprez CHIC41Health, F-59655 
Villeuneve d'Ascq, France.
(4)Univ. Lille, CNRS, Centrale Lille, Univ. Artois, UMR 8181, Unité de Catalyse 
et Chimie du Solide (UCCS), F-59000 Lille, France.

Sesquiterpene lactones (STLs) are a large group of terpenoids most commonly 
found in plants of the Asteraceae family, e.g., in chicory plants, displaying a 
wide range of interesting biological activities. However, further studies on the 
biological potential of chicory-derived STLs and analogues are challenging as 
only four of these molecules are commercially available (as analytical 
standards), and to date, there are no published or patented simple 
extraction-purification processes capable of large-scale STLs isolation. In this 
work, we describe a novel three-step large-scale extraction and purification 
method for the simultaneous purification of 11,13-dihydrolactucin (DHLc) and 
lactucin (Lc) starting from a chicory genotype rich in these STLs and the 
corresponding glucosyl and oxalyl conjugated forms. After a small-scale 
screening on 100 mg of freeze-dried chicory root powder, the best results were 
achieved with a 17 h water maceration at 30 °C. With these conditions, we 
managed to increase the content of DHLc and Lc, at the same time favoring the 
hydrolysis of their conjugated forms. On a larger scale, the extraction of 750 g 
of freeze-dried chicory root powder, followed by a liquid-liquid extraction step 
and a reversed-phase chromatography, allowed the recovery of 642.3 ± 76.3 mg of 
DHLc and 175.3 ± 32.9 mg of Lc. The two pure STLs were subsequently used in the 
context of semisynthesis to generate analogues for biological evaluation as 
antibacterial agents. In addition, other described chicory STLs that are not 
commercially available were also synthesized or extracted to serve as analytical 
standards for the study. In particular, lactucin-oxalate and 
11,13-dihydrolactucin-oxalate were synthesized in two steps starting from Lc and 
DHLc, respectively. On the other hand, 11β,13-dihydrolactucin-glucoside was 
obtained after a MeOH/H2O (70/30) extraction, followed by a liquid-liquid 
extraction step and a reversed-phase chromatography. Together, this work will 
help facilitate the evaluation of the biological potential of chicory-derived 
STLs and their semisynthetic analogues.

DOI: 10.3390/ph16050771
PMCID: PMC10222082
PMID: 37242554

Conflict of interest statement: The authors declare no conflict of interest.


5. Front Nutr. 2022 Dec 19;9:1082698. doi: 10.3389/fnut.2022.1082698. eCollection
 2022.

Overlapping activation pattern of bitter taste receptors affect sensory 
adaptation and food perception.

Lang R(1), Lang T(1), Dunkel A(1), Ziegler F(1), Behrens M(1).

Author information:
(1)Leibniz Institute for Food Systems Biology at the Technical University of 
Munich, Freising, Germany.

The composition of menus and the sequence of foodstuffs consumed during a meal 
underlies elaborate rules. However, the molecular foundations for the observed 
taste- and pleasure-raising effects of complex menus are obscure. The molecular 
identification and characterization of taste receptors can help to gain insight 
into the complex interrelationships of food items and beverages during meals. In 
our study, we quantified important bitter compounds in chicory and chicory-based 
surrogate coffee and used them to identify responsive bitter taste receptors. 
The two receptors, TAS2R43 and TAS2R46, are exquisitely sensitive to lactucin, 
lactucopicrin, and 11β,13-dihydrolactucin. Sensory testing demonstrated a 
profound influence of the sequence of consumption of chicory, surrogate coffee, 
and roasted coffee on the perceived bitterness by human volunteers. These 
findings pave the way for a molecular understanding of some of the mixture 
effects underlying empirical meal compositions.

Copyright © 2022 Lang, Lang, Dunkel, Ziegler and Behrens.

DOI: 10.3389/fnut.2022.1082698
PMCID: PMC9806268
PMID: 36601079

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest.