Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Food Sci Nutr. 2024 Apr 18;12(8):5357-5372. doi: 10.1002/fsn3.4176.
eCollection  2024 Aug.

Lactucopicrin promotes fatty acid β-oxidation and attenuates lipid accumulation 
through adenosine monophosphate-activated protein kinase activation in free 
fatty acid-induced human hepatoblastoma cancer cells.

Tan H(1)(2), Mi N(3), Tong F(1), Zhang R(1), Abudurexiti A(1), Lei Y(1), Zhong 
Y(1), Yan J(1), Yang J(1), Ma X(1).

Author information:
(1)College of Pharmacy Xinjiang Medical University Urumqi Xinjiang China.
(2)Affiliated Hospital of Chongqing Three Gorges Medical College Chongqing 
China.
(3)The First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang 
China.

With its annually increasing prevalence, non-alcoholic fatty liver disease 
(NAFLD) has become a serious threat to people's life and health. After a 
preliminary research, we found that Lactucopicrin has pharmacological effects, 
such as lowering blood lipids and protecting the liver. Further research showed 
its significant activation for fatty acid β-oxidase hydroxyacyl-coenzyme A (CoA) 
dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), so we 
hypothesized that Lactucopicrin could ameliorate lipid accumulation in 
hepatocytes by promoting fatty acid β-oxidation. In this study, free fatty acid 
(FFA)-induced human hepatoblastoma cancer cells (HepG2) were used to establish 
an in vitro NAFLD model to investigate the molecular basis of Lactucopicrin in 
regulating lipid metabolism. Staining with Oil red O and measurements of 
triglyceride (TG) content, fatty acid β-oxidase (FaβO) activity, reactive oxygen 
species (ROS) content, mitochondrial membrane potential, and adenosine 
triphosphate (ATP) content were used to assess the extent to which Lactucopicrin 
ameliorates lipid accumulation and promotes fatty acid β-oxidation. Quantitative 
real-time polymerase chain reaction (qRT-PCR) and Western blot methods were used 
to explore the regulatory effects of Lactucopicrin on factors related to fatty 
acid β-oxidation. Results showed that Lactucopicrin downregulated phosphorylated 
mammalian target of rapamycin (P-mTOR) by activating the adenosine 
monophosphate-activated protein kinase (AMPK) pathway and upregulated the 
messenger RNA (mRNA) and protein expression levels of coactivators (peroxisome 
proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)), 
transcription factors (peroxisome proliferator-activated receptor α (PPARα) and 
peroxisome proliferator-activated receptor γ (PPARγ)), and oxidative factors 
(carnitine palmitoyltransferase 1A (CPT1A) and HADHA). This phenomenon resulted 
in a significant increase in FaβO activity, ATP content, and JC-1 and a 
significant decrease in ROS level, TG content, and intracellular lipid droplets. 
With the addition of Dorsomorphin, all the effects of Lactucopicrin intervention 
were suppressed. In summary, Lactucopicrin promotes fatty acid β-oxidation by 
activating the AMPK pathway, thereby ameliorating FFA-induced intracellular 
lipid accumulation in HepG2 cells.

© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.

DOI: 10.1002/fsn3.4176
PMCID: PMC11317671
PMID: 39139977

Conflict of interest statement: All authors certify that they have participated 
sufficiently in the work to take public responsibility for the appropriateness 
of the experimental design and method, and the collection, analysis, and 
interpretation of the data. The authors have reviewed the final version of the 
manuscript and approved it for publication. To the best of our knowledge and 
belief, this manuscript has not been published in whole or in part nor is it 
being considered for publication elsewhere.


2. Chem Biodivers. 2024 Aug 13:e202400993. doi: 10.1002/cbdv.202400993. Online 
ahead of print.

Study on Active Components and Mechanism of Lettuce Latex Against Spodoptera 
Litura.

Gu C(1), Zeng B(1), Wang M(1), Zhang Y(1), Yan C(1), Lin Y(1), Khan A(2), Zeng 
R(3), Song Y(3).

Author information:
(1)Key Laboratory of Ministry of Education for Genetics, Breeding and Multiple 
Utilization of Crops, College of Life Sciences, Fujian Agriculture and Forestry 
University, Fuzhou, 350002, China.
(2)Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 
Abbottabad, 22060, Pakistan.
(3)Laboratory of Ministry of Agriculture and Rural Affairs of Biological 
Breeding for Fujian and Taiwan Crops, College of Agriculture, Fujian Agriculture 
and Forestry University, Fuzhou, 350002, China.

Plant latex is a sticky emulsion exuded from laticifers once the plant is 
damaged. Latex is an essential component of plant defense against herbivores. 
Lettuce (Lactuca sativa L.) in the Compositae family has relatively fewer insect 
herbivores compared with other leaf vegetables. The larvae of a generalist 
lepidopteran pest Spodoptera litura (Fabricius) avoided feeding on living 
lettuce plants. However, the larvae rapidly damaged the excised leaves that were 
unable to produce latex. Six compounds were isolated from lettuce latex. They 
were identified as 2,5-dihydroxybenzaldehyde (1), 
3β-hydroxy-4,15-dehydrograndolide (2), annuolide D (3), lactucin (4), 
lactucopicrin (5), and hanphyllin (6). Bioassays showed that the inhibition rate 
of compound 1 (2,5-dihydroxybenzaldehyde) and 6 (hanphyllin, a sesquiterpene 
lactone) on the weight gain of S. litura were 52.4 % and 10 %, respectively, at 
the concentration of 100 μg/g. RNA-seq analyses showed that larval exposure to 
compound 1 down-regulated the genes associated with heterobiotic metabolism 
including drug metabolism-cytochrome P450, metabolism of xenobiotics by 
cytochrome P450, retinol metabolism, glutathione metabolism, and drug 
metabolism-other enzymes (mainly uridine diphosphate glucuronyltransferase, 
UGTs). RT-qPCR further confirmed that 33 genes in the family of carboxylesterase 
(CarE), P450s and UGTs were down-regulated by compound 1. The activities of 
CarE, P450s and UGTs in the larvae fed on diets containing compound 1 were 
significantly lower than those fed on control diets, with the inhibition for the 
three detoxification enzymes being 55.4 %, 53.9 %, and 52.9 %. These findings 
suggest that secondary metabolites including 2,5-dihydroxybenzaldehyde in the 
latex play a key role in protecting lettuce from insect herbivory.

© 2024 Wiley-VHCA AG, Zurich, Switzerland.

DOI: 10.1002/cbdv.202400993
PMID: 39136195


3. J Sci Food Agric. 2024 Nov;104(14):9046-9055. doi: 10.1002/jsfa.13731. Epub
2024  Jul 9.

Short-term high-light intensity and low temperature improve the quality and 
flavor of lettuce grown in plant factory.

Zhang L(#)(1), Zhang Q(#)(2), Escalona Contreras VH(3), Huang T(1), Jiang H(1), 
Song B(1), Duan Z(1), Li Y(1), Yang X(1), Song H(2), Yang Q(1).

Author information:
(1)Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, 
Chengdu National Agricultural Science and Technology Center, Chengdu, China.
(2)College of Horticulture and Landscape Architecture, Southwest University, 
Chongqing, China.
(3)Centro de Estudios Postcosecha, Facultad de Ciencias Agronómicas, Universidad 
de Chile, Santiago, Chile.
(#)Contributed equally

BACKGROUND: Lettuce holds a prominent position in the year-round supply of 
vegetables, offering a rich array of health-beneficial substances, such as 
dietary fiber, phenolic compounds, lactucopicrin and lactucin. As such, its 
flavor has garnered increasing attention. Balancing the enhancement of 
beneficial compounds with the reduction of undesirable taste is a key focus of 
scientific research. To investigate short-term management to improve the 
nutritional quality and flavor of lettuce, combinations of different light 
intensities (200, 500 and 800 μm ol m-2 s-1) and temperatures (10 and 22 °C) 
were applied separately to 'Lollo Rosso' and 'Little Butter Lettuce' for 7 days 
before harvest.
RESULTS: The results obtained showed that increasing light intensity at low 
temperatures decreased nitrate content and increased soluble sugar, soluble 
protein, anthocyanin and phenolic compound content. In the case of lettuce 
flavor, the bitterness-related metabolites such as lactucin and lactucopicrin 
were reduced with high light intensity at a low temperature of 10 °C. With this 
combination, the fructose and glucose contents increased, significantly 
improving lettuce flavor.
CONCLUSION: Higher light intensity combined with low temperature for 7 days 
before harvest effectively improved the nutritional quality and flavor of 
lettuce, suggesting its great potential for use in horticultural practices. © 
2024 Society of Chemical Industry.

© 2024 Society of Chemical Industry.

DOI: 10.1002/jsfa.13731
PMID: 38979943 [Indexed for MEDLINE]


4. ACS Omega. 2024 Apr 18;9(17):19401-19417. doi: 10.1021/acsomega.4c00699. 
eCollection 2024 Apr 30.

Screening of α-Glucosidase Inhibitors in Cichorium glandulosum Boiss. et Huet 
Extracts and Study of Interaction Mechanisms.

Abudurexiti A(1), Abdurahman A(1), Zhang R(1), Zhong Y(1), Lei Y(1), Qi S(1), 
Hou W(1), Ma X(1).

Author information:
(1)School of Pharmacy, Xin Jiang Medical University, Urumqi 830054, China.

Cichorium glandulosum Boiss. et Huet (CGB) extract has an α-glucosidase 
inhibitory effect (IC50 = 59.34 ± 0.07 μg/mL, positive control drug acarbose 
IC50 = 126.1 ± 0.02 μg/mL), but the precise enzyme inhibitors implicated in this 
process are not known. The screening of α-glucosidase inhibitors in CGB extracts 
was conducted by bioaffinity ultrafiltration, and six potential inhibitors 
(quercetin, lactucin, 3-O-methylquercetin, hyperoside, lactucopicrin, and 
isochlorogenic acid B) were screened as the precise inhibitors. The binding rate 
calculations and evaluation of enzyme inhibitory effects showed that lactucin 
and lactucopicrin exhibited the greatest inhibitory activities. Next, the 
inhibiting effects of the active components of CGB, lactucin and lactucopicrin, 
on α-glucosidase and their mechanisms were investigated through α-glucosidase 
activity assay, enzyme kinetics, multispectral analysis, and molecular docking 
simulation. The findings demonstrated that lactucin (IC50 = 52.76 ± 0.21 μM) and 
lactucopicrin (IC50 = 17.71 ± 0.64 μM) exhibited more inhibitory effects on 
α-glucosidase in comparison to acarbose (positive drug, IC50 = 195.2 ± 0.30 μM). 
Enzyme kinetic research revealed that lactucin inhibits α-glucosidase through a 
noncompetitive inhibition mechanism, while lactucopicrin inhibits it through a 
competitive inhibition mechanism. The fluorescence results suggested that 
lactucin and lactucopicrin effectively reduce the fluorescence of α-glucosidase 
by creating lactucin-α-glucosidase and lactucopicrin-α-glucosidase complexes 
through static quenching. Furthermore, the circular dichroism (CD) and Fourier 
transform infrared spectroscopy (FT-IR) analyses revealed that the interaction 
between lactucin or lactucopicrin and α-glucosidase resulted in a modification 
of the α-glucosidase's conformation. The findings from molecular docking and 
molecular dynamics simulations offer further confirmation that lactucopicrin has 
a robust binding affinity for certain residues located within the active cavity 
of α-glucosidase. Furthermore, it has a greater affinity for α-glucosidase 
compared to lactucin. The results validate the suppressive impact of lactucin 
and lactucopicrin on α-glucosidase and elucidate their underlying processes. 
Additionally, they serve as a foundation for the structural alteration of 
sesquiterpene derived from CGB, with the intention of using it for the 
management of diabetic mellitus.

© 2024 The Authors. Published by American Chemical Society.

DOI: 10.1021/acsomega.4c00699
PMCID: PMC11064185
PMID: 38708260

Conflict of interest statement: The authors declare no competing financial 
interest.


5. Comput Biol Chem. 2024 Jun;110:108088. doi:
10.1016/j.compbiolchem.2024.108088.  Epub 2024 Apr 26.

Screening of the effective sites of Cichorium glandulosum against hyperuricemia 
combined with hyperlipidemia and its network pharmacology analysis.

Yang Z(1), Lyu B(2), Ma B(1), Gao Y(3), Qin D(4).

Author information:
(1)Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry 
of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 
832002, China.
(2)The First Affiliated Hospital of School of Medicine, Shihezi 
University, Shihezi, Xinjiang 832000, China.
(3)College of Applied Engineering, Henan University of Science and 
Technology, Sanmenxia, Henan 472000, China.
(4)Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry 
of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 
832002, China. Electronic address: qdm_pha@shzu.edu.cn.

Cichorium glandulosum, a common traditional Chinese medicine used by Uyghur and 
Mongolian ethnic groups, is recognized for its potential to ameliorate metabolic 
disorders. However, the specific efficacy and mechanisms of Cichorium 
glandulosum in treating the comorbidity of hyperuricaemia and hyperlipidaemia 
remain unexplored. This study aims to explore the pharmacological effects and 
mechanisms of Cichorium glandulosum on this comorbidity through a combination of 
animal experiments, network pharmacology, and molecular docking techniques. A 
rat model of hyperuricaemia combined with hyperlipidaemia was established 
through a high-fat and high-purine diet, and the effective parts of the aqueous 
extract of Cichorium glandulosum to reduce uric acid and lipid levels were 
screened and the components of the parts were analysed by LC-MS/MS. The active 
components, core targets, and key pathways were analysed using network 
pharmacology and validated by molecular docking. Animal experimental results 
indicated that the n-butanol extract of Cichorium glandulosum showed a 
significant therapeutic effect on this comorbidity. Analysis of the n-butanol 
extract yielded 35 active ingredients and 138 intersecting targets related to 
diseases. Key targets identified through compound-target-pathway (C-T-P) and 
Protein-Protein Interaction (PPI) analyses included RELA, CASP3, PTGS2, TNF, and 
ESR1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) 
pathway enrichment analyses revealed 2515 functional items and 164 pathways, 
respectively. Molecular docking demonstrated that isochlorogenic acid A, 
baicalin, chicoric acid, and lactucopicrin showed the highest binding affinity 
to RELA and PTGS2. The n-butanol fraction from the aqueous extract of Cichorium 
glandulosum was found to reduce uric acid and lipid levels effectively. In 
summary, Cichorium glandulosum has a therapeutic effect on hyperuricaemia 
combined with hyperlipidaemia through its multi-component, multi-target, and 
multi-pathway characteristics.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.compbiolchem.2024.108088
PMID: 38685167 [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