Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Epilepsy Res. 2024 Sep;205:107421. doi: 10.1016/j.eplepsyres.2024.107421. Epub
 2024 Jul 26.

Effects of acute administration of 4-allyl-2,6-dimethoxyphenol in mouse models 
of seizures.

Ribeiro LR(1), Dos Santos AMF(2), da Cruz Guedes E(3), Bezerra TLDS(4), de Souza 
TL(4), Filho JMB(5), de Almeida RN(6), Salvadori MGDSS(7).

Author information:
(1)Laboratory of Psychopharmacology, Federal University of Paraíba, João Pessoa, 
Brazil; Graduate Program in Cognitive Neuroscience and Behavior, Federal 
University of Paraíba, João Pessoa, Brazil; Department of Psychology, Federal 
University of Paraíba, João Pessoa, Brazil; Institute of Research in 
Pharmaceuticals and Medicines, Federal University of Paraíba, João Pessoa, 
Brazil. Electronic address: leandrorodrigoribeiro@yahoo.com.br.
(2)Laboratory of Psychopharmacology, Federal University of Paraíba, João Pessoa, 
Brazil; Graduate Program in Cognitive Neuroscience and Behavior, Federal 
University of Paraíba, João Pessoa, Brazil; Institute of Research in 
Pharmaceuticals and Medicines, Federal University of Paraíba, João Pessoa, 
Brazil.
(3)Laboratory of Psychopharmacology, Federal University of Paraíba, João Pessoa, 
Brazil; Institute of Research in Pharmaceuticals and Medicines, Federal 
University of Paraíba, João Pessoa, Brazil; Graduate Program in Natural and 
Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, 
Brazil.
(4)Laboratory of Psychopharmacology, Federal University of Paraíba, João Pessoa, 
Brazil; Institute of Research in Pharmaceuticals and Medicines, Federal 
University of Paraíba, João Pessoa, Brazil.
(5)Institute of Research in Pharmaceuticals and Medicines, Federal University of 
Paraíba, João Pessoa, Brazil; Graduate Program in Natural and Synthetic 
Bioactive Products, Federal University of Paraíba, João Pessoa, Brazil; 
Department of Pharmaceutical Sciences, Federal University of Paraíba, João 
Pessoa, Brazil.
(6)Laboratory of Psychopharmacology, Federal University of Paraíba, João Pessoa, 
Brazil; Graduate Program in Cognitive Neuroscience and Behavior, Federal 
University of Paraíba, João Pessoa, Brazil; Institute of Research in 
Pharmaceuticals and Medicines, Federal University of Paraíba, João Pessoa, 
Brazil; Graduate Program in Natural and Synthetic Bioactive Products, Federal 
University of Paraíba, João Pessoa, Brazil; Department of Physiology and 
Pathology, Federal University of Paraíba, João Pessoa, Brazil.
(7)Laboratory of Psychopharmacology, Federal University of Paraíba, João Pessoa, 
Brazil; Graduate Program in Cognitive Neuroscience and Behavior, Federal 
University of Paraíba, João Pessoa, Brazil; Department of Psychology, Federal 
University of Paraíba, João Pessoa, Brazil; Institute of Research in 
Pharmaceuticals and Medicines, Federal University of Paraíba, João Pessoa, 
Brazil; Graduate Program in Natural and Synthetic Bioactive Products, Federal 
University of Paraíba, João Pessoa, Brazil.

Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked 
seizures, presents a substantial challenge in approximately one-third of cases 
exhibiting resistance to conventional pharmacological treatments. This study 
investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound 
derived from various natural sources, in different models of induced seizures 
and its impact on animal electroencephalographic (EEG) recordings. Adult male 
Swiss albino mice were pre-treated (i.p.) with a dose curve of 
4-allyl-2,6-dimethoxyphenol (50, 100, or 200 mg/kg), its vehicle (Tween), or 
standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice 
were subjected to different seizure-inducing models - pentylenetetrazole (PTZ), 
3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock 
seizure (MES). EEG analysis was performed on other animals surgically implanted 
with electrodes to evaluate brain activity. Significant results revealed that 
animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to 
the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the 
first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total 
duration of tonic-clonic seizures in the PTZ and PILO models; decreased 
intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished 
mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase 
in the percentage of total power attributed to beta waves following 
4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected 
from behavioral and electrographic seizures in the PTZ model, preventing 
increases in the average amplitude of recording signals while also inducing an 
increase in the participation of theta and gamma waves. These findings suggest 
promising outcomes for the tested phenolic compound across diverse pre-clinical 
seizure models, highlighting the need for further comprehensive studies to 
elucidate its underlying mechanisms and validate its clinical relevance in 
epilepsy management.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.eplepsyres.2024.107421
PMID: 39068729 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors 
declare no conflicts of interest, financial or personal, that could have 
influenced the findings presented in this paper.


2. Int J Biol Macromol. 2023 Jul 1;242(Pt 3):124947. doi: 
10.1016/j.ijbiomac.2023.124947. Epub 2023 May 19.

Allyl halide induced electrochemical degradation of lignin into double-bonded 
phenolic monomers.

Wu Z(1), Zhang X(1), Fan H(2), Han X(1), Wen Y(1), Li G(3), Li H(1).

Author information:
(1)Hebei Provincial Key Lab of Green Chemical Technology & High Efficient Energy 
Saving, School of Chemical Engineering and Technology, Hebei University of 
Technology, Tianjin 300130, China.
(2)Hebei Provincial Key Lab of Green Chemical Technology & High Efficient Energy 
Saving, School of Chemical Engineering and Technology, Hebei University of 
Technology, Tianjin 300130, China. Electronic address: fanhongxian@hebut.edu.cn.
(3)Hebei Provincial Key Lab of Green Chemical Technology & High Efficient Energy 
Saving, School of Chemical Engineering and Technology, Hebei University of 
Technology, Tianjin 300130, China. Electronic address: ligang@hebut.edu.cn.

Lignin is one of the major macromolecule in nature that contains an aromatic 
ring structure, and also a potential source of high-value products such as 
biofuels and chemicals. However, Lignin is a kind of complex heterogeneous 
polymer which can produce many degradation products during processing or 
treatment. These degradation products are difficult to separate, making it 
challenging to use lignin directly for high-value applications. This study 
proposes an electrocatalytic method to degrade lignin by using allyl halides to 
induce double-bonded phenolic monomers, while avoiding separation. In an 
alkaline solution, the three basic structural units (G, S, and H) of lignin were 
transformed into phenolic monomers by introducing allyl halide, which could 
effectively expand lignin application space. This reaction was achieved using a 
Pb/PbO2 electrode as the anode and copper as the cathode. It was further 
confirmed that double-bonded phenolic monomers were obtained by degradation. 
3-allylbromide has more active allyl radicals and significantly higher product 
yields than 3-allylchloride. The yields of 4-allyl-2-methoxyphenol, 
4-allyl-2,6-dimethoxyphenol and 2-allylphenol could reach 17.21 g/kg-lignin, 
7.75 g/kg-lignin, and 0.67 g/kg-lignin respectively. These mixed double-bond 
monomers can be used as monomer materials for in-situ polymerization without 
further separation, which lays the foundation for high value-added applications 
of lignin.

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

DOI: 10.1016/j.ijbiomac.2023.124947
PMID: 37211078 [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.


3. Inflammation. 2022 Aug;45(4):1534-1547. doi: 10.1007/s10753-022-01639-8. Epub 
2022 Mar 10.

Methoxyeugenol Protects Against Lung Inflammation and Suppresses Neutrophil 
Extracellular Trap Formation in an LPS-Induced Acute Lung Injury Model.

Antunes GL(1), Matzenbacher LS(2), Costa BP(2), de Sousa Basso B(2), Levorse 
VGS(2), Antunes KH(3), Costa-Ferro ZSM(4), de Oliveira JR(2).

Author information:
(1)Laboratory of Cellular Biophysics and Inflammation, Pontifical Catholic 
University of Rio Grande Do Sul (PUCRS), 6690 Ipiranga Ave, Porto Alegre, RS, 
90610-000, Brazil. gessica.antunes@edu.pucrs.br.
(2)Laboratory of Cellular Biophysics and Inflammation, Pontifical Catholic 
University of Rio Grande Do Sul (PUCRS), 6690 Ipiranga Ave, Porto Alegre, RS, 
90610-000, Brazil.
(3)Laboratory of Clinical and Experimental Immunology, Pontifical Catholic 
University of Rio Grande Do Sul (PUCRS), Porto Alegre, Brazil.
(4)Brain Institute of Rio Grande Do Sul (BraIns), Pontifical Catholic University 
of Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil.

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with 
high rates of morbidity and mortality worldwide. 4-Allyl-2,6-dimethoxyphenol 
(methoxyeugenol), a phenylpropanoid from a synthetic source, exhibits strong 
anti-inflammatory activity, but its effects on the inflammation of ALI have not 
yet been reported. In our study, the anti-inflammatory effects of methoxyeugenol 
were investigated on RAW 264.7 cells and a mice model of ALI. Our results showed 
that methoxyeugenol (7.5 and 30 µM) attenuated the proliferation and gene 
expression of interleukin (IL)-6 in LPS-stimulated RAW 264.7 cells. In a mice 
model of ALI induced with LPS, methoxyeugenol exhibited a significant protective 
effect, based on influx reduction of macrophages and neutrophils into the lungs; 
reduction in release of the cytokines IL-6, TNF-α, and IL-10; and in reactive 
oxygen species (ROS) formation. We show that the anti-inflammatory effects of 
methoxyeugenol are associated with the suppression of the NFκB signaling 
pathway. Moreover, we demonstrated for the first time that a phenolic compound, 
from a synthetic source, protects against lung tissue inflammation and promotes 
a reduction of NET formation. These findings provided evidence for the use of 
methoxyeugenol as a new strategy to control inflammation in ALI disease.

© 2022. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s10753-022-01639-8
PMID: 35267122 [Indexed for MEDLINE]


4. Phytomedicine. 2021 Feb;82:153445. doi: 10.1016/j.phymed.2020.153445. Epub
2020  Dec 25.

n-BuOH extract of Bletilla striata exerts chemopreventive effects on lung 
against SiO(2) nanoparticles through activation of Nrf2 pathway.

Chen G(1), Chang W(2), Li X(3), Han L(4), Zhou D(2), Feng Y(2), Li B(2), Zhu 
F(5), Li N(6).

Author information:
(1)School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical 
University, Shenyang 110016, China; State Key Laboratory of Phytochemistry and 
Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of 
Sciences, Kunming China.
(2)School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical 
University, Shenyang 110016, China.
(3)Department of PIVAS, Yanbian University Hospital, Yanji, China.
(4)Department of Phathology, Yanbian University Hospital, Yanji, China.
(5)State Key Laboratory of Phytochemistry and Plant Resources in West China, 
Kunming Institute of Botany, Chinese Academy of Sciences, Kunming China.
(6)School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical 
University, Shenyang 110016, China. Electronic address: liningsypharm@163.com.

BACKGROUND: SiO2 nanoparticles (nm SiO2) are ubiquitous in daily life and are 
acknowledged to be detrimental to human health. Bletilla striata is a 
traditional medicine used for generations in China and its polysaccharide has 
the anti-pulmonary fibrosis effect.
PURPOSE: To investigate the lung protective effect of the small molecules 
(n-BuOH extract) of B. striata and clarify the underlying mechanism.
STUDY DESIGN AND METHODS: C57BL/6 mice were subjected to intratracheal 
instillation with nm SiO2 nanoparticle suspension (7 mg/kg) to construct the in 
vivo model of nm SiO2-induced lung injury. The chemical profile of the n-BuOH 
extract of B. striata was investigated by HPLC analysis using authentic samples 
isolated from B. striata. Gymnoside II with the most potent chemoprotective 
capacity in the n-BuOH extract was used to clarify the potential bio-active 
molecular basis of the n-BuOH extract using in vitro experiments. The 
cytotoxicity, apoptosis, oxidative stress, and the Nrf2 signaling pathway were 
examined in SiO2-induced A549 cells. ML385 was adopted to down-regulate the Nrf2 
expression.
RESULTS: The n-BuOH extract of B. striata (40 mg/kg) could alleviate the 
SiO2-induced lung injury by increasing Nrf2 expression and thereby suppressing 
Bax/Bcl-2 pathway in the nm SiO2-induced mice model. The chemical profile study 
showed that militarine, gymnoside II, and 4-allyl-2, 6-dimethoxyphenol glucoside 
were the main constituents of n-BuOH extract. Studies on gymnoside II revealed 
that it could partially restore the SiO2-induced decline in cell viability while 
did not affect the growth of normal A549 cells within the concentration range of 
1-50 μM, suggesting a protective effect against nm SiO2 in lung A549 cells. The 
hoechst 33258 staining, flow cytometry, and western blot experiments 
demonstrated that gymnoside II (25 μM) could partially reverse the SiO2-induced 
cell apoptosis and ROS production by enhancing Nrf2, HO-1, and γ-GCSc 
expressions and Nrf2 silencing by ML385 abrogated the effects of gymnoside II 
(25 μM) on apoptosis and ROS production in A549 cells.
CONCLUSION: The present study suggests that in addition to the polysaccharide, 
small molecules (n-BuOH extract) of B. striata can also elicit a protective 
effect on lung injuries through the Nrf2-dependent mechanism and gymnoside II is 
one of the main bio-active constituents contributing to the n-BuOH 
extract-elicited lung protective effect against nm SiO2.

Copyright © 2020 Elsevier GmbH. All rights reserved.

DOI: 10.1016/j.phymed.2020.153445
PMID: 33418138 [Indexed for MEDLINE]


5. J Agric Food Chem. 2021 Jan 13;69(1):126-134. doi: 10.1021/acs.jafc.0c05945. 
Epub 2021 Jan 4.

OBP2 in the Midlegs of the Male Bactrocera dorsalis Is Involved in the 
Perception of the Female-Biased Sex Pheromone 4-Allyl-2,6-dimethoxyphenol.

Hu L(1), Chen B(1), Liu K(1), Yu G(1), Chen Y(1), Dai J(2), Zhao X(3), Zhong 
G(4), Zhang Y(5), Shen J(1).

Author information:
(1)Institute of Plant Health, ZhongKai University of Agriculture and 
Engineering, 510225 Guangzhou, Guangdong, China.
(2)Guangdong Key Laboratory of Animal Conservation and Resource Utilization, 
Guangdong Public Laboratory of Wild Animal Conservation and Utilization, 
Guangzhou, Guangdong China.
(3)College of Light industry and Food Science, ZhongKai University of 
Agriculture and Engineering, Guangzhou, Guangdong China.
(4)Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of 
Education, South China Agricultural University, Guangzhou, China.
(5)Department of Plant Protection, Institute of Vegetables and Flowers, Chinese 
Academy of Agricultural Sciences, 100081 Beijing, China.

Short-range semiochemicals convey individual-specific information, which is 
important for final successful courtship and copulation. In this study, an 
electroantennography (EAG) instrument was used to determine the legs of male 
Bactrocera dorsalis that might participate in the perception of 
4-allyl-2,6-dimethoxyphenol (4-DMP), a female-biased cuticular hydrocarbon (CHC) 
component. By performing comparative RNA-seq analysis, nine differentially 
expressed OBPs between 4-DMP-stimulated (M4-DMP) and unstimulated (M) male flies 
were screened out. Among the four downregulated OBPs, BdorOBP2 exhibited the 
strongest binding to 4-DMP than BdorOBP4, BdorOBP19a, and BdorOBP56h. Functional 
analyses confirmed that the reduction in transcript abundance of BdorOBP2 led to 
a significant decrease in behavioral responses of male flies to 4-DMP. In silico 
simulation revealed dramatic changes in the key residues and conformation 
between the two complexes, implying that BdorOBP2 might activate different 
receptors after binding to 4-DMP or methyl eugenol (ME). The results of this 
study suggest that BdorOBP2 mediates behavioral responses to 4-DMP and could be 
a promising molecular target for strategies of pest control.

DOI: 10.1021/acs.jafc.0c05945
PMID: 33393782 [Indexed for MEDLINE]