Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Environ Sci Pollut Res Int. 2024 Aug;31(39):51870-51882. doi: 
10.1007/s11356-024-34688-7. Epub 2024 Aug 12.

Excess copper promotes an increase in the concentration of metabolites in Tridax 
procumbens L.

Chitolina SF(1), Dartora N(2), de Pelegrin CMG(1)(3), Dos Santos MV(1)(3), 
Cassol F(1)(3), Friedrich T(1), da Veiga JD(1), Borkowski JE(1), Vieira IAM(1).

Author information:
(1)Universidade Federal da Fronteira Sul (UFFS), Sala 109, Laboratório 2, Campus 
Cerro Largo, Cerro Largo, RS, CEP 97900-000, Brazil.
(2)Universidade Federal da Fronteira Sul (UFFS), Sala 109, Laboratório 2, Campus 
Cerro Largo, Cerro Largo, RS, CEP 97900-000, Brazil. 
nessana.dartora@uffs.edu.br.
(3)Programa de Pós-Graduação Em Ambientes E Tecnologias Sustentáveis (UFFS), 
Unidade Seminário, Sala 1-2-16, Campus Cerro Largo, Cerro Largo, RS, CEP 
97900-000, Brazil.

The study investigated the effects of cultivating Tridax procumbens in 
hydroponic conditions with different concentrations of copper ions, aiming to 
understand the physiological changes and the impact on the biosynthesis of 
secondary metabolites. The treatments consisted of a completely randomized 
design, with five increasing concentrations of copper (T0 = 0.235, T1 = 12.5, 
T2 = 25, T3 = 50, T4 = 100 µmol L-1 of Cu), under controlled conditions for 
36 days. Analysis of bioactive compounds in leaves was performed by HPLC-DAD and 
ESI-MS. Several phenolic compounds, alkaloids, phytosterols and triterpenoids 
were identified, demonstrating the plant's metabolic plasticity. The highest 
dose of copper (100 µmol L-1) significantly promoted voacangine, the most 
predominant compound in the analyses. Notably, 66.7% of the metabolites that 
showed an increase in concentration, were phenolic compounds. Furthermore, 
treatments with 12.5 and 25 µmol L-1 of copper were identified as promoting the 
biosynthesis of phytosterols and triterpenoids. These biochemical adaptations 
can play a fundamental role in the survival and development of plants in 
environments contaminated by metals, and from this it is possible to determine 
cultivation techniques that maximize the biosynthesis of the compound of 
interest.

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
part of Springer Nature.

DOI: 10.1007/s11356-024-34688-7
PMID: 39134796 [Indexed for MEDLINE]


2. J Appl Toxicol. 2024 Aug;44(8):1246-1256. doi: 10.1002/jat.4615. Epub 2024 Apr
 26.

Voacangine protects hippocampal neuronal cells against oxygen-glucose 
deprivation/reoxygenation-caused oxidative stress and ferroptosis by activating 
the PI3K-Akt-FoxO signaling.

Li Y(1), Sun Y(1), Wang J(1), Wang X(1), Yang W(2).

Author information:
(1)Medical College, Zhengzhou University of Industrial Technology, No. 16 
Xueyuan Road, Xinzheng, Henan Province, 451100, China.
(2)College of Public Health, Zhengzhou University, No. 164 Kexue Road, 
Zhengzhou, Henan Province, 450001, China.

Voacangine, a naturally occurring alkaloid, has been testified to display 
beneficial effects on a variety of human diseases, but its role in ischemic 
stroke is unclear. The impacts of voacangine on oxygen-glucose 
deprivation/reoxygenation (OGD/R)-tempted hippocampal neuronal cells are 
investigated. The bioinformatics analysis found that voacangine is a bioactive 
ingredient that may have good effects on ischemic stroke. KEGG pathways analysis 
found that voacangine may regulate ischemic stroke through modulating the 
PI3K-Akt-FoxO signaling pathway. Voacangine could mitigate OGD/R-tempted 
cytotoxicity in HT22 cells. Voacangine mitigated OGD/R-tempted oxidative stress 
in HT22 cells by diminishing reactive oxygen species level and enhancing 
superoxide dismutase level. Voacangine mitigated OGD/R-tempted ferroptosis in 
HT22 cells. Voacangine promoted activation of the PI3K-Akt-FoxO signaling in 
OGD/R-induced HT22 cells. Inactivation of the PI3K-Akt-FoxO signaling pathway 
reversed the protective effects of voacangine against OGD/R-tempted oxidative 
stress, cytotoxicity, and ferroptosis in HT22 cells. In conclusion, voacangine 
protects hippocampal neuronal cells against OGD/R-caused oxidative stress and 
ferroptosis by activating the PI3K-Akt-FoxO signaling.

© 2024 John Wiley & Sons Ltd.

DOI: 10.1002/jat.4615
PMID: 38666302 [Indexed for MEDLINE]


3. Environ Toxicol. 2024 Jul;39(7):4004-4013. doi: 10.1002/tox.24274. Epub 2024
Apr  12.

Voacangine mitigates oxidative stress and neuroinflammation in middle cerebral 
artery occlusion-induced cerebral ischemia/reperfusion injury by averting the 
NF-κBp65/MAPK signaling pathways in rats.

Xu B(1), Wu H(2), Guo W(1), Hussain SA(3), Wang T(4).

Author information:
(1)Department of General Medicine, Shaanxi Provincial People's Hospital, Xi'an, 
China.
(2)Shaanxi Provincial Center for Diseases Control and Prevention, Xi'an, China.
(3)Department of Zoology, College of Science, King Saud University, Riyadh, 
Saudi Arabia.
(4)Department of Geratology, Shaanxi Provincial People's Hospital, Xi'an, China.

Ischemic stroke is a leading cause of human mortality. Cerebral 
ischemia-reperfusion injury (CI/RI) is a primary cause of stroke. 
Ischemia-reperfusion (I/R) resulting in oxidative stress and inflammatory events 
may lead to severe neuronal impairments. Thus, anti-oxidative and 
anti-inflammatory mediators that can alleviate post-I/R neuronal injuries are 
required for the treatment of CI/RI. An alkaloid, voacangine (VCG) is a 
recognized antioxidant, anti-inflammatory, and anticancer agent. Hence, the 
current study intended to explore the neuroprotective potential and the 
principal mechanisms of VCG in CI/RI. The experimental rats were divided into 
four sets: control, I/R-induced, I/R + VCG (2.5 mg/kg), I/R + VCG (5 mg/kg). 
CI/RI was induced by implanting a thread into the middle cerebral artery 
occlusion (MCAO) model. Brain damages were assessed on the basis of brain edema, 
brain infarct volume, neurological deficit score, histopathology, oxidative 
stress, and neuroinflammation. Results revealed that VCG inhibited the 
triggering of NLRP3 inflammasome, pro-inflammatory cytokines, lipid 
peroxidation, but enhanced the antioxidant status in MCAO rats. Furthermore, VCG 
treatment averted brain damage by I/R, neuroinflammation, and oxidative stress 
by suppressing NF-κBp65/MAPK pathways. The results of the study provide 
pertinent insights pertaining to the role of VCG as a potential neuroprotective 
agent against ischemic stroke.

© 2024 Wiley Periodicals LLC.

DOI: 10.1002/tox.24274
PMID: 38606816 [Indexed for MEDLINE]


4. Evid Based Complement Alternat Med. 2024 Jan 3;2024:5513141. doi: 
10.1155/2024/5513141. eCollection 2024.

Phytochemistry Profile, Antimicrobial and Antitumor Potential of the Methanolic 
Extract of Tabernaemontana catharinensis A DC and Eragrostis plana NEES.

da Rosa E(1), Stopiglia CDO(2), Machado MM(2), Filho ACD(1), Soci UPR(3), Mendez 
ASL(4), Fernandes T(3), de Oliveira EM(3), Moreira CM(1).

Author information:
(1)Programa de Pós-Graduação em Bioquímica, Universidade Federal do 
Pampa-UNIPAMPA, Uruguaiana, RS, Brazil.
(2)Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do 
Pampa-UNIPAMPA, Uruguaiana, RS, Brazil.
(3)Laboratório de Bioquímica e Biologia Molecular do Exercício, Escola de 
Educação Física e Esporte, Universidade de São Paulo-USP, São Paulo, SP, Brazil.
(4)Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do 
Rio Grande do Sul-UFRGS, Porto Alegre, RS, Brazil.

Natural compounds that have the potential to act as antimicrobials and 
antitumors are a constant search in the field of pharmacotherapy. Eragrostis 
plana NEES (Poaceae) is a grass with high allelopathic potential. Allelopathy is 
associated with compounds generated in the primary and secondary metabolism of 
the plant, which act to protect it from phytopathogens. Tabernaemontana 
catharinensis A DC (Apocynaceae), a tree in which its leaves and bark are used 
for the preparation of extracts and infusions that have anti-inflammatory and 
antinociceptive effects, is attributed to its phytochemical constitution. The 
objective of this study was to elucidate the phytochemical constitution, the 
antibacterial potential, the toxicity against immune system cells, hemolytic 
potential, and antitumor effect of methanolic extracts of E. plana and T. 
catharinensis. The phytochemical investigation was carried out using the 
UHPLC-QTOF MS equipment. The antibacterial activity was tested using the broth 
microdilution plate assay, against Gram-negative and Gram-positive strains, and 
cytotoxicity assays were performed on human peripheral blood mononuclear cells 
(PBMC) and in vitro hemolysis. Antitumor activity was performed against the 
colon cancer cell line (CT26). Results were expressed as mean and standard 
deviation and analyzed by ANOVA. p < 0.05 was considered significant. More than 
19 possible phytochemical constituents were identified for each plant, with 
emphasis on phenolic compounds (acids: vanillic, caffeic, and quinic) and 
alkaloids (alstovenine, rhyncophylline, amezepine, voacangine, and 
coronaridine). Both extracts showed antibacterial activity at concentrations 
below 500 µg/mL and were able to decrease the viability of CT26 at 
concentrations below 2000 µg/mL, without showing cytotoxic effect on PBMCs and 
in vitro hemolysis at the highest concentration tested. This is the first report 
of the activity of E. plana and T. catharinensis extracts against colon cancer 
cell line (CT26). Studies should be carried out to verify possible molecular 
targets involved in the antitumor effect in vivo.

Copyright © 2024 Emanoeli da Rosa et al.

DOI: 10.1155/2024/5513141
PMCID: PMC10781527
PMID: 38213844

Conflict of interest statement: The authors declare that there are no conflicts 
of interest.


5. Fitoterapia. 2023 Sep;169:105602. doi: 10.1016/j.fitote.2023.105602. Epub 2023
 Jul 7.

Central nervous system activity of a Tabernaemontana arborea alkaloid extract 
involves serotonergic and opioidergic neurotransmission in murine models.

González-Trujano ME(1), Páez-Martínez N(2), Krengel F(3), Martínez-Vargas D(4), 
León-Santiago M(5), Cruz-López B(6), Puentes-Guerrero JM(1), Díaz-Cantón JK(5), 
Reyes-Chilpa R(7), Guzmán-Gutiérrez SL(8).

Author information:
(1)Laboratorio de Neurofarmacología de Productos Naturales, Dirección de 
Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la 
Fuente Muñiz", Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Ciudad de 
México 14370, Mexico.
(2)Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto 
Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón, Col. Casco de 
Santo Tomas, Ciudad de México 11340, Mexico; Laboratorio Integrativo Para el 
Estudio de Sustancias Inhalables Adictivas, Dirección de Investigaciones en 
Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", 
Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Ciudad de México 14370, 
Mexico.
(3)Laboratorio de Fitoquímica, Departamento de Ecología y Recursos Naturales, 
Facultad de Ciencias, UNAM. Av. Universidad 3000, Circuito Exterior s/n, 
Alcaldía Coyoacán, CP 04510, Ciudad Universitaria, CDMX, Mexico.
(4)Laboratorio de Neurofisiología del Control y la Regulación, Dirección de 
Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la 
Fuente Muñiz", Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Ciudad de 
México 14370, Mexico.
(5)Instituto de Química, Universidad Nacional Autónoma de México, Ciudad 
Universitaria, Av. Universidad 3000, Circuito Exterior S/N, Delegación Coyoacán, 
C.P. 04510, Ciudad Universitaria, Ciudad de México, Mexico.
(6)Laboratorio Integrativo Para el Estudio de Sustancias Inhalables Adictivas, 
Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría 
"Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, Col. San Lorenzo 
Huipulco, Ciudad de México 14370, Mexico.
(7)Instituto de Química, Universidad Nacional Autónoma de México, Ciudad 
Universitaria, Av. Universidad 3000, Circuito Exterior S/N, Delegación Coyoacán, 
C.P. 04510, Ciudad Universitaria, Ciudad de México, Mexico. Electronic address: 
chilpa@unam.mx.
(8)CONAHCyT-Instituto de Investigaciones Biomédicas, Universidad Nacional 
Autónoma de México, Av. Universidad 3000, Circuito Escolar S/N, Delegación 
Coyoacán, C.P. 04510, Ciudad Universitaria, Ciudad de México, Mexico. Electronic 
address: saguzmangu@conahcyt.mx.

Tabernaemontana arborea (Apocynaceae) is a Mexican tree species known to contain 
ibogan type alkaloids. This study aimed at determining central nervous 
system-related activities of an alkaloid extract obtained from the root bark of 
T. arborea. A gas chromatography-mass spectrometry (GC-MS) analysis was 
performed to describe the alkaloid profile of the extract. A wide dosing range 
(0.1 to 56.2 mg/kg) of this extract was evaluated in different murine models. 
Electrical brain activity was examined by electroencephalography (EEG). The 
extract's effects on motor coordination, ambulatory activity, and memory were 
analyzed based on the rotarod, open field (OFT), and object recognition tests 
(ORT), respectively. Antidepressant and antinociceptive activities were 
determined using the forced swimming test (FST) and the formalin assay, 
respectively. In order to elucidate the underlying mechanisms of action, the 
5-HT1A receptor antagonist WAY100635 (1 mg/kg) or the opioid receptor antagonist 
naloxone (1 mg/kg) was included in the latter experiments. GC-MS analysis (μg/mg 
extract) confirmed the presence of the monoterpenoid indole alkaloids (MIAs) 
voacangine (207.00), ibogaine (106.33), vobasine (72.81), coronaridine (30.72), 
and ibogamine (24.2) as principal constituents of the extract, which exhibited 
dose- and receptor-dependent antidepressant (0.1 to 1 mg/kg; 5-HT1A) and 
antinociceptive (30 and 56.2 mg/kg; opioid) effects, without altering motor 
coordination, ambulatory activity, and memory. EEG indicated CNS depressant 
activity at high doses (30 and 56.2 mg/kg). The root bark of T. arborea contains 
a mixture of alkaloids that may hold therapeutic value in pain relief and the 
treatment of psychiatric diseases without causing neurotoxic activity at 
effective doses.

Copyright © 2023 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.fitote.2023.105602
PMID: 37423501 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors 
declare no conflict of interest.