Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. CNS Neurosci Ther. 2024 Nov;30(11):e70099. doi: 10.1111/cns.70099.

CB1 Receptor Activation Provides Neuroprotection in an Animal Model of 
Glutamate-Induced Excitotoxicity Through a Reduction of NOX-2 Activity and 
Oxidative Stress.

Martínez-Torres AM(1), Morán J(1).

Author information:
(1)División de Neurociencias, Instituto de Fisiología Celular, Universidad 
Nacional Autónoma de México, Ciudad de México, Mexico.

BACKGROUND: Excitotoxicity is a process in which NADPH oxidase-2 (NOX-2) plays a 
pivotal role in the generation of reactive oxygen species (ROS). Oxidative 
stress influences the expression of Aquaporin 4 (AQP4), a water channel 
implicated in blood-brain barrier (BBB) permeability and edema formation. The 
endocannabinoid system is widely distributed in the brain, particularly through 
the cannabinoid receptor type 1 (CB1) and type 2 (CB2), which have been shown to 
have a neuroprotective function in brain injury. Given the significant 
involvement of NOX-2 in ROS production during excitotoxicity, our research aims 
to assess the participation of NOX-2 in the neuroprotective effect of the 
cannabinoid receptor agonist WIN55,212-2 against glutamate-induced 
excitotoxicity damage in the striatum using in vivo model.
METHODS: Wild-type mice (C57BL/6) and NOX-2 KO (gp91Cybbtm1Din/J) were 
stereotactically injected in the striatum with monosodium glutamate or vehicle. 
Subsequently, a group of mice was administered an intraperitoneal dose of 
WIN55,212-2, AM251, or AM251/WIN55,212-2 following the intracerebral injection. 
Motor activity was assessed, and the lesion was examined through histological 
sections stained with cresyl violet. Additionally, brain water content and Evans 
blue assay were conducted. The activity of NOX was quantified, and the protein 
expression of CB1, gp91phox, AQP4, Iba-1, TNF-α, and NF-κB was analyzed using 
Western blot. Furthermore, ROS formation was measured through the DHE assay.
RESULTS: The activation of the endocannabinoid receptors demonstrated a 
neuroprotective response during excitotoxicity, meditated by NOX-2. The 
reduction in ROS production led to a decrease in neuroinflammation, and AQP4 
expression, resulting in reduced edema formation, and BBB permeability.
CONCLUSIONS: During excitotoxic damage, WIN55,212-2 inhibits NOX-2-induced ROS 
production, reducing brain injury.

© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & 
Sons Ltd.

DOI: 10.1111/cns.70099
PMCID: PMC11534500
PMID: 39496572 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that the research was 
conducted without any commercial or financial relationships that could be 
construed as a potential conflict of interest.


2. Environ Pollut. 2024 Oct 26:125199. doi: 10.1016/j.envpol.2024.125199. Online 
ahead of print.

Fuel fumes and foliage: the fate of speciated gasoline VOCs during 
phytoremediation and their impact on the bacterial phenotype.

Matheson S(1), Fleck R(2), Lockwood T(3), Gill RL(4), Lyu L(5), Irga PJ(5), 
Torpy FR(2).

Author information:
(1)Plants and Environmental Quality Research Group (PEQR), School of Life 
Sciences, Faculty of Science, University of Technology Sydney, Australia. 
Electronic address: Stephen.Matheson@uts.edu.au.
(2)Plants and Environmental Quality Research Group (PEQR), School of Life 
Sciences, Faculty of Science, University of Technology Sydney, Australia.
(3)Hyphenated Mass Spectrometry Laboratory (HyMaS), School of Mathematical and 
Physical Sciences, Faculty of Science, University of Technology Sydney, 
Australia.
(4)Plants and Environmental Quality Research Group (PEQR), School of Life 
Sciences, Faculty of Science, University of Technology Sydney, Australia; 
Productive Coasts, Climate Change Cluster, Faculty of Science, University of 
Technology Sydney, Australia.
(5)Plants and Environmental Quality Research Group (PEQR), School of Civil and 
Environmental Engineering, Faculty of Engineering and Information Technology, 
University of Technology Sydney, Australia.

The capacity of indoor plants including green walls to capture, deposit and 
remediate individual volatile organic compounds (VOCs) has been well documented. 
However, in realistic settings, plant systems are exposed to a complex mixture 
of VOCs from highly varied various emission sources. Gasoline vapour is one of 
the major sources of these emissions, containing high concentrations of the 
carcinogens benzene, toluene, ethylbenzene and xylene (BTEX). Using both solid 
phase micro extraction (SPME) and quick, easy, cheap, effective, rugged and safe 
(QuEChERS) sampling techniques, we assessed the dynamics of individual speciated 
gasoline VOC phytoremediation from the air and uptake within green wall plant 
species and growth substrates within a small passive green wall system, along 
with quantifying the phenotypic changes within the plant-associated bacterial 
communities resulting from gasoline exposure. Over 8 hours the green wall system 
achieved 100% removal of atmospheric benzene, 1,2,3-trimethyl, eicosane and 
hexadecane, benzene 1,3-diethyl-; 1,3,5 cycloheptatriene,7- ethyl and carbonic 
acid eicosyl vinyl ester. All plant species tested demonstrated the accumulation 
45 petrochemical VOCs (pVOCs) with Spathiphyllum wallisii successfully 
accumulating the majority of pVOC functional groups after 24 h of gasoline 
exposure. Within the plants phyllospheric bacterial communities, changes in both 
cellular complexity and granularity appeared to increase as a result of gasoline 
exposure, while cell size diminished. This work provides novel findings on the 
VOC removal processes of botanical systems for realistic and highly toxic VOC 
profiles.

Copyright © 2024. Published by Elsevier Ltd.

DOI: 10.1016/j.envpol.2024.125199
PMID: 39490663

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.


3. BMC Chem. 2024 Nov 1;18(1):213. doi: 10.1186/s13065-024-01325-w.

Bioassay-guided isolation and in Silico characterization of cytotoxic compounds 
from Hemimycale sp. Sponge targeting A549 lung cancer cells.

Said AAE(1), Abdel-Rahman IM(2), Mostafa YA(3), Attia EZ(1), Samy MN(1), 
Abdelmohsen UR(4)(5), Matsunami K(6), Fouad MA(1), Gouda YG(7).

Author information:
(1)Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, 
61519, Egypt.
(2)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya 
University, New-Minia, 61111, Egypt.
(3)Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut 
University, Assiut, 71526, Egypt.
(4)Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, 
61519, Egypt. usama.ramadan@mu.edu.eg.
(5)Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, 
Universities Zone, New Minia City, 61111, Egypt. usama.ramadan@mu.edu.eg.
(6)Graduate School of Biomedical and Health Sciences, Hiroshima University, 
1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
(7)Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, 
71526, Egypt.

Bioassay-guided fractionation approach led to identification of two novel 
compounds; (4-(hydroxymethyl)-3-methoxy-1H-pyrazol (1) and mycalene (2), 
alongside with four known metabolites; octadecane (3), hexatriacontane (4), 
1-heneicosanol (5) and heptatriacontanoic acid (6) from the Red Sea marine 
sponge Hemimycale sp. The ethyl acetate fraction showed a noticeable cytotoxic 
activity against the lung cancer cell line (A549) with IC50 value of 75.54 µg/ 
mL. Structural elucidation was achieved using a combination of 1D and 2D nuclear 
magnetic resonance (NMR) spectroscopy and high-resolution electrospray 
ionization-mass spectrometry (HR-ESI-MS). To elucidate the potential mechanism 
of action behind the cytotoxic effects against lung cancer, a multi-faceted 
approach combining in silico network pharmacology, experimental validation, and 
molecular docking studies were employed. Both compounds, designated as 1 and 2, 
demonstrated significant binding affinities to predicted target proteins, with 
docking scores of -4.789 and - 4.421 kcal/mol, respectively. These results lay 
the groundwork for further investigation into the therapeutic potential of these 
novel compounds from Hemimycale sp. as promising candidates for lung cancer 
treatment.

© 2024. The Author(s).

DOI: 10.1186/s13065-024-01325-w
PMCID: PMC11531136
PMID: 39487510

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


4. J Med Chem. 2024 Nov 2. doi: 10.1021/acs.jmedchem.4c01113. Online ahead of 
print.

Azobenzene-Tagged Photopeptides Exhibiting Excellent Selectivity and 
Light-Induced Cytotoxicity in MCF-7 Cells over HeLa and A549.

Pradhan S(1), Sarker S(1), Thilagar P(1).

Author information:
(1)Department of Inorganic and Physical Chemistry, Indian Institute of Science, 
Bangalore 560012, INDIA.

The precise regulation of proteasome activity has become a focal point in 
current research, particularly its implications in cancer treatment. Bortezomib 
is used for treating multiple myeloma and is found to be ineffective against 
solid tumors. A spatiotemporal control over the proteasome is one of the 
solutions to resolve these issues using external stimuli, such as light. Thus, 
we designed and synthesized azobenzene-containing tripeptide vinyl sulfones 1, 
2, 3, and 4, as the azobenzene moiety can impart E↔Z isomerism upon exposure to 
UV light. Further, the hydrophobicity of these peptides was fine-tuned by 
systematically varying the size of hydrophobic amino acids at the P1, P2, and P3 
positions. The light-induced Z isomers of these photopeptides showed excellent 
cellular potency in HeLa, MCF-7, and A549 cell lines. Photopeptide 4 with valine 
at the proximal position, phenylalanine at P2, and leucine at the P1 positions 
exhibited 19.3- and 6.6-fold cellular potency in MCF-7 and A549 cells, 
respectively.

DOI: 10.1021/acs.jmedchem.4c01113
PMID: 39487790


5. J Mol Recognit. 2024 Oct 31:e3110. doi: 10.1002/jmr.3110. Online ahead of
print.

Probing the Molecular Basis of Aminoacyl-Adenylate Affinity With Mycobacterium 
tuberculosis Leucyl-tRNA Synthetase Employing Molecular Dynamics, Umbrella 
Sampling Simulations and Site-Directed Mutagenesis.

Volynets GP(1)(2), Gudzera OI(3), Usenko MO(4), Gorbatiuk OB(4), Bdzhola VG(1), 
Kotey IM(1), Balanda AO(1), Prykhod'ko AO(1)(2), Lukashov SS(1), Chuk OA(5), 
Skydanovych OI(3), Yaremchuk GD(3), Yarmoluk SM(1), Tukalo MA(3).

Author information:
(1)Department of Medicinal Chemistry, Institute of Molecular Biology and 
Genetics, the NAS of Ukraine, Kyiv, Ukraine.
(2)Scientific Services Company Otava Ltd., Kyiv, Ukraine.
(3)Department of Protein Synthesis Enzymology, Institute of Molecular Biology 
and Genetics, the NAS of Ukraine, Kyiv, Ukraine.
(4)Department of Cell Regulatory Mechanisms, Institute of Molecular Biology and 
Genetics, the NAS of Ukraine, Kyiv, Ukraine.
(5)Kyiv Academic University, Kyiv, Ukraine.

Leucyl-tRNA synthetase (LeuRS) is clinically validated molecular target for 
antibiotic development. Recently, we have reported several classes of 
small-molecular inhibitors targeting aminoacyl-adenylate binding site of 
Mycobacterium tuberculosis LeuRS with antibacterial activity. In this work, we 
performed in silico site-directed mutagenesis of M. tuberculosis LeuRS synthetic 
site in order to identify the most critical amino acid residues for the 
interaction with substrate and prove binding modes of inhibitors. We carried out 
20-ns molecular dynamics (MD) simulations and used umbrella sampling (US) method 
for the calculation of the binding free energy (ΔGb) of leucyl-adenylate with 
wild-type and mutated forms of LeuRS. According to molecular modeling results, 
it was found that His89, Tyr93, and Glu660 are essential amino acid residues 
both for aminoacyl-adenylate affinity and hydrogen bond formation. We have 
selected His89 for experimental site-directed mutagenesis since according to our 
previous molecular docking results this amino acid residue was predicted to be 
important for inhibitor interaction in adenine-binding region. We obtained 
recombinant mutant M. tuberculosis LeuRS H89A. Using aminoacylation assay we 
have found that the mutation of His89 to Ala in the active site of M. 
tuberculosis LeuRS results in significant decrease of inhibitory activity for 
compounds belonging to three different chemical 
classes-3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazoles, 
N-benzylidene-N'-thiazol-2-yl-hydrazines, and 
1-oxo-1H-isothiochromene-3-carboxylic acid (4-phenyl-thiazol-2-yl)-amide 
derivatives. Therefore, the interaction with His89 should be taken into account 
during further M. tuberculosis LeuRS inhibitors development and optimization.

© 2024 John Wiley & Sons Ltd.

DOI: 10.1002/jmr.3110
PMID: 39478352