Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Food Chem. 2024 Oct 9;464(Pt 1):141560. doi: 10.1016/j.foodchem.2024.141560. 
Online ahead of print.

Exploring synergistic inhibitory mechanisms of flavonoid mixtures on 
α-glucosidase by experimental analysis and molecular dynamics simulation.

Pan J(1), Nawaz M(1), Liu J(1), Liu H(1), Lv Z(1), Yang W(1), Jiao Z(2), Zhang 
Q(3).

Author information:
(1)National Key Laboratory for Germplasm Innovation & Utilization of 
Horticultural Crops, Zhengzhou Fruit Research Institute, Chinese Academy of 
Agricultural Sciences, Zhengzhou 450009, Henan, China.
(2)National Key Laboratory for Germplasm Innovation & Utilization of 
Horticultural Crops, Zhengzhou Fruit Research Institute, Chinese Academy of 
Agricultural Sciences, Zhengzhou 450009, Henan, China. Electronic address: 
jiaozhonggao@caas.cn.
(3)National Key Laboratory for Germplasm Innovation & Utilization of 
Horticultural Crops, Zhengzhou Fruit Research Institute, Chinese Academy of 
Agricultural Sciences, Zhengzhou 450009, Henan, China. Electronic address: 
zhangqiang02@caas.cn.

The study was the first to evaluate the synergistic interaction of luteolin + 
quercetin, luteolin + 3-O-methylquercetin, and quercetin + 3-O-methylquercetin 
mixtures on α-glucosidase and the binding mechanisms were explored using both 
experimental and theoretical approaches. The results showed that three flavonoid 
mixtures exhibited a mixed type of inhibition and demonstrated the most potent 
synergistic effects on α-glucosidase inhibition at 6:4 ratio, with interaction 
index (γ) of 0.85, 0.78 and 0.73, respectively. The three mixtures had a great 
influence on α-glucosidase secondary structures. Molecular simulation further 
demonstrated that three flavonoid mixtures formed hydrophobic interactions and 
hydrogen bonds with amino acid residues at different sites of α-glucosidase. 
Collectively, luteolin + quercetin, luteolin + 3-O-methylquercetin and quercetin 
+ 3-O-methylquercetin were found to inhibit α-glucosidase in a synergistic 
manner and can be potentially used for the development of hypoglycemic food 
products.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.foodchem.2024.141560
PMID: 39396467

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.


2. 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.


3. J Agric Food Chem. 2024 Mar 13;72(10):5477-5490. doi:
10.1021/acs.jafc.3c07139.  Epub 2024 Feb 28.

Integrated Metabolomics and Transcriptomics Analyses Highlight the Flavonoid 
Compounds Response to Alkaline Salt Stress in Glycyrrhiza uralensis Leaves.

Lv X(1)(2), Zhu L(3), Ma D(3), Zhang F(3), Cai Z(4), Bai H(2), Hui J(2), Li 
S(2), Xu X(1), Li M(5).

Author information:
(1)College of Forestry and Prataculture, Ningxia University, Yinchuan 750021, 
China.
(2)Agricultural Biotechnology Research Center, Ningxia Academy of Agriculture 
and Forestry Sciences, Yinchuan 750002, China.
(3)College of Ecology and Environment, Ningxia University, Yinchuan 750021, 
China.
(4)Department of Life and Food Science, Ningxia University, Yinchuan 750021, 
China.
(5)Institute of Forestry and Grassland Ecology, Ningxia Academy of Agriculture 
and Forestry Sciences, Yinchuan 750002, China.

Glycyrrhiza uralensis is a saline-alkali-tolerant plant whose aerial parts are 
rich in flavonoids; however, the role of these flavonoids in saline-alkali 
tolerance remains unclear. Herein, we performed physiological, metabolomics, and 
transcriptomics analyses in G. uralensis leaves under alkaline salt stress for 
different durations. Alkaline salt stress stimulated excessive accumulation of 
reactive oxygen species and consequently destroyed the cell membrane, causing 
cell death, and G. uralensis initiated osmotic regulation and the antioxidant 
system to respond to stress. In total, 803 metabolites, including 244 
flavonoids, were detected via metabolomics analysis. Differentially altered 
metabolites and differentially expressed genes were coenriched in 
flavonoid-related pathways. Genes such as novel.4890, Glyur001511s00039602, and 
Glyur000775s00025737 were highly expressed, and flavonoid metabolites such as 
2'-hydroxygenistein, apigenin, and 3-O-methylquercetin were upregulated. Thus, 
flavonoids as nonenzymatic antioxidants play an important role in stress 
tolerance. These findings provide novel insights into the response of G. 
uralensis to alkaline salt stress.

DOI: 10.1021/acs.jafc.3c07139
PMID: 38416716 [Indexed for MEDLINE]


4. Nat Prod Res. 2024 Jan 8:1-6. doi: 10.1080/14786419.2023.2300402. Online ahead
 of print.

Flavones isolated from Pseudognaphalium liebmannii with tracheal smooth muscle 
relaxant properties.

Navarrete A(1)(2), Balderas-López JL(1), Rosas-Canales JG(1), Tapia-Álvarez 
GR(1), Alfaro-Romero A(3), Aviles-Rosas VH(1), Rodríguez-Ramos F(4), Avula B(2), 
Khan IA(2)(5).

Author information:
(1)Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma 
de México, Ciudad Universitaria, Coyoacán, Ciudad de México, México.
(2)National Center for Natural Products Research, School of Pharmacy, University 
of MS, University, MS, USA.
(3)Preparatoria SantaTeresa, Universidad LaSalle Campus Ciudad de México, 
Tlalpan, Ciudad de México, México.
(4)Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la 
Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México, 
Mexico.
(5)Division of Pharmacognosy, Department of BioMolecular Sciences, School of 
Pharmacy, University of Mississippi, University, MS, USA.

The inflorescences of Pseudognaphalium liebmannii are used as folk medicine to 
treat various respiratory diseases. In this work, we report the isolation of 
seven known flavones: 5-hydroxy-3,7-dimethoxyflavone 1, 
5,8-dihydroxy-3,7-dimethoxyflavone 2, 5,7-dihydroxy-3,8-dimethoxyflavone 3 
(gnaphaliin A), 3,5-dihydroxy-7,8-dimethoxyflavone 4 (gnaphaliin B), 
3,5-dihydroxy-6,7,8-trimethoxyflavone 5, 3,5,7-trimethoxyflavone 6 and 
3-O-methylquercetin 7. All these flavones except 1 and 6 showed a relaxant 
effect on guinea pig tracheal preparation with EC50 between 69.91 ± 15.32 and 
118.72 ± 7.06 µM. Aminophylline (EC50 = 122.03 ± 7.05 µM) was used as a relaxant 
reference drug. The active flavones shifted the concentration-response curves of 
forskolin and nitroprusside leftward, and significantly reduced the EC50 values 
of these drugs. Furthermore, these flavones dose-dependently inhibited 
phosphodiesterase (PDE) in an in vitro assay. This reveals that the 
inflorescences of P. liebmannii contain several flavones with relaxant effect on 
airway smooth muscle and with PDEs inhibition that contribute to supporting the 
anti-asthmatic traditional use.

DOI: 10.1080/14786419.2023.2300402
PMID: 38189356


5. ACS Omega. 2023 Oct 18;8(43):40764-40774. doi: 10.1021/acsomega.3c05841. 
eCollection 2023 Oct 31.

Structural and Anticancer Studies of Methoxyflavone Derivative from Strychnos 
pseudoquina A.St.-Hil. (Loganiaceae) from Brazilian Cerrado.

Silva MC(1), Cunha G(2), Firmino P(3), Sallum LO(1), Menezes A(2), Dutra J(4), 
de Araujo-Neto J(5), Batista AA(4), Ellena J(3), Napolitano HB(6).

Author information:
(1)Laboratório de Novos Materiais, Universidade Evangélica de Goiás, 75083-515 
Anápolis, GO, Brazil.
(2)Laboratório de Produtos Naturais, Universidade Estadual de Goiás, 75132-903 
Anápolis, GO, Brazil.
(3)Laboratório Multiusuário de Cristalografia Estrutural, Instituto de Física de 
São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil.
(4)Laboratório de Estrutura e Reatividade de Compostos Inorgânicos, Departamento 
de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, 
Brazil.
(5)Laboratório de Bioinorgânica, Catálise e Farmacologia, Instituto de Química, 
Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
(6)Grupo de Química Teórica e Estrutural de Anápolis, Universidade Estadual de 
Goiás, 75132-903 Anápolis, GO, Brazil.

The Cerrado biome is the world's largest and most diversified tropical savanna. 
Despite its diversity, there remains a paucity of scientific discussion and 
evidence about the medicinal use of Cerrado plants. One of the greatest 
challenges is the complexity of secondary metabolites, such as flavonoids, 
present in those plants and their extraction, purification, and 
characterization, which involves a wide range of approaches, tools, and 
techniques. Notwithstanding these difficulties, the search for accurately proven 
medicinal plants against cancer, a leading cause of death worldwide, has 
contributed to this growing area of research. This study set out to extract, 
purify, and characterize 3-O-methylquercetin isolated from the plant Strychnos 
pseudoquina A.St.-Hil. (Loganiaceae) and to test it for antiproliferative 
activity and selectivity against different tumor and nontumor human cell lines. 
A combined-method approach was employed using 1H and 13C nuclear magnetic 
resonance, thermogravimetric analysis, differential scanning calorimetry, 
single-crystal X-ray diffraction, Hirshfeld surface analysis, and theoretical 
calculations to extensively characterize this bioflavonoid. 3-O-methylquercetin 
melts around 275 °C and crystallizes in a nonplanar conformation with an angle 
of 18.02° between the pyran ring (C) and the phenyl ring (B), unlike quercetin 
and luteolin, which are planar. Finally, the in vitro cytotoxicity of 
3-O-methylquercetin was compared with data from quercetin, luteolin, and 
cisplatin, showing that structural differences influenced the antiproliferative 
activity and the selectivity against different tumor cell lines.

© 2023 The Authors. Published by American Chemical Society.

DOI: 10.1021/acsomega.3c05841
PMCID: PMC10621014
PMID: 37929093

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