Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Pharmaceuticals (Basel). 2024 Oct 5;17(10):1331. doi: 10.3390/ph17101331.

Analgesic and Anti-Arthritic Potential of Methanolic Extract and Palmatine 
Obtained from Annona squamosa Leaves.

Ito CNA(1), Santos Procopio ED(1), Balsalobre NM(1), Machado LL(2), Silva-Filho 
SE(2), Pedroso TF(3), Lourenço CC(3), Oliveira RJ(4), Arena AC(5), Salvador 
MJ(3), Kassuya CAL(1).

Author information:
(1)Health Sciences College, Federal University of Grande Dourados (UFGD), 
Dourados 79804-970, MS, Brazil.
(2)Pharmaceutical Sciences, Food and Nutrition College, Federal University of 
Mato Grosso do Sul (UFMS), Campo Grande 79070-900, MS, Brazil.
(3)Institute of Biology, Department of Plant Biology, University of Campinas 
(UNICAMP), Campinas 13083-862, SP, Brazil.
(4)Stem Cell, Cell Therapy and Toxicological Genetics Research Centre 
(CeTroGen), Medical School, Federal University of Mato Grosso do Sul (UFMS), 
Campo Grande 79070-900, MS, Brazil.
(5)Institute of Biosciences of Botucatu, Department of Structural and Functional 
Biology, São Paulo State University (UNESP), Botucatu 18618-970, SP, Brazil.

Background/Objectives: Annona squamosa is used in folk medicine to treat pain 
and arthritis. Palmatine is an alkaloid isolated from several plants, including 
A. squamosa leaves. The aim of the present study was to investigate the 
analgesic, anti-arthritic, and anti-inflammatory potential of the methanolic 
extract of A. squamosa (EMAS) and palmatine. Methods: The chemical profile of 
EMAS was evaluated by ultra high-performance liquid chromatography with 
electrospray ionization coupled to mass spectrometry (UHPLC-ESI/MS). EMAS and 
palmatine were evaluated in carrageenan-induced pleurisy, zymosan-induced joint 
inflammation, formalin-induced nociception, and tumor necrosis factor 
(TNF)-induced mechanical hyperalgesia in experimental models in mice. A 
cytotoxicity test of EMAS and palmatine was performed using a 
methylthiazolidiphenyl-tetrazolium (MTT) bromide assay. Results: The analysis of 
the chemical profile of the extract showed the presence of palmatine, 
liriodenine, and anonaine. Oral administration of EMAS and palmatine 
significantly reduced leukocyte migration and oxide nitric production in the 
carrageenan-induced pleurisy model. EMAS and palmatine reduced mechanical 
hyperalgesia, leukocyte migration, and edema formation in the joint inflammation 
induced by zymosan. In the formalin test, palmatine was effective against the 
second-phase nociceptive response, mechanical hyperalgesia, and cold allodynia. 
In addition, palmatine reduced mechanical hyperalgesia induced by TNF. EMAS and 
palmatine did not demonstrate cytotoxicity. Conclusions: The present study 
showed that A. squamosa and palmatine are analgesic and anti-inflammatory 
agents, and that the anti-hyperalgesic properties of palmatine may involve the 
TNF pathway. Palmatine may be one of the compounds responsible for the 
anti-hyperalgesic and/or anti-arthritic properties of this medicinal plant.

DOI: 10.3390/ph17101331
PMCID: PMC11510468
PMID: 39458972

Conflict of interest statement: The authors declare no conflicts of interest.


2. Int J Biol Macromol. 2024 Sep 20;280(Pt 2):135870. doi: 
10.1016/j.ijbiomac.2024.135870. Online ahead of print.

Confocal image of three oxoaporphine alkaloids in cancer cell lines and their 
interaction with DNA by multispectroscopic and molecular docking techniques.

Kong LT(1), Zhao CY(1), Xin HY(2), Gu WY(1), Su YX(1), Jia XH(3), Tang WZ(4).

Author information:
(1)School of Pharmacy & Institute of Materia Medica, Shandong First Medical 
University & Shandong Academy of Medical Sciences, NHC Key Laboratory of 
Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & 
Uncommon Diseases of Shandong Province, Jinan 250117, China.
(2)School of Clinical and Basic Medical Sciences, Shandong First Medical 
University and Shandong Academy of Medical Sciences, Jinan 250117, China.
(3)School of Pharmacy & Institute of Materia Medica, Shandong First Medical 
University & Shandong Academy of Medical Sciences, NHC Key Laboratory of 
Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & 
Uncommon Diseases of Shandong Province, Jinan 250117, China. Electronic address: 
imjxh@163.com.
(4)School of Pharmacy & Institute of Materia Medica, Shandong First Medical 
University & Shandong Academy of Medical Sciences, NHC Key Laboratory of 
Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & 
Uncommon Diseases of Shandong Province, Jinan 250117, China. Electronic address: 
tangwenzhao@sdfmu.edu.cn.

Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural 
oxoaporphine alkaloids (OAs), which revealed significant biological activity 
such as anticancer, anti-inflammatory and antimicrobial activities and were 
considered as potential lead compounds for the development of new clinical 
chemicals. In the present study, confocal laser scanning fluorescence microscopy 
observation demonstrated these three natural OAs could traverse inside of the 
nucleus and get an opportunity to interact with DNA. Their interaction 
properties with DNA were then investigated simultaneously by two spectral 
fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as 
UV-vis absorption and cyclic voltammetry measurements, and further verified by 
the molecular docking analysis. Results indicated Di and Li were distinctly 
classified as the intercalative molecules to DNA, however, Ly was confirmed with 
a mixed-mode binding of partial intercalation and groove affinity. Their binding 
ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with 
their structural changes. Thermodynamic studies revealed the binding process of 
Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the 
major binding force for Li-ctDNA complex, however, the interaction between Ly 
and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular 
docking provided detailed computational interaction of Di, Li and Ly with DNA, 
which proved the intercalation binding of Li-DNA complex and Di-DNA complex 
stabilizing mainly by the π-π binding force, however, apart from a small 
quantity of π-π interaction, another binding force in the Ly-DNA complex mainly 
was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.ijbiomac.2024.135870
PMID: 39307493

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. Fitoterapia. 2024 Apr;174:105868. doi: 10.1016/j.fitote.2024.105868. Epub 2024
 Feb 18.

Four unreported aporphine alkaloids with antifungal activities from Artabotrys 
hexapetalus.

Zhao P(1), Yu Z(2), Huang JP(3), Wang L(2), Huang SX(4), Yang J(5).

Author information:
(1)College of Ethnic Medicine, Chengdu University of Traditional Chinese 
Medicine, Chengdu, China; State Key Laboratory of Phytochemistry and Plant 
Resources in West China, Kunming Institute of Botany, Chinese Academy of 
Sciences, Kunming, China; Yinchuan Hospital of Traditional Chinese Medicine, 
Yinchuan, China.
(2)College of Ethnic Medicine, Chengdu University of Traditional Chinese 
Medicine, Chengdu, China.
(3)State Key Laboratory of Phytochemistry and Plant Resources in West China, 
Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
(4)College of Ethnic Medicine, Chengdu University of Traditional Chinese 
Medicine, Chengdu, China; State Key Laboratory of Phytochemistry and Plant 
Resources in West China, Kunming Institute of Botany, Chinese Academy of 
Sciences, Kunming, China. Electronic address: sxhuang@mail.kib.ac.cn.
(5)State Key Laboratory of Phytochemistry and Plant Resources in West China, 
Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. 
Electronic address: yangjingc@mail.kib.ac.cn.

In this study, the extract from Artabotrys hexapetalus showed strong antifungal 
activity against phytopathogenic fungi in vitro. Four unreported aporphine 
alkaloids, hexapetalusine A-D (1-4), were isolated from stems and roots of 
Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids 
(5-10). Their chemical structures were elucidated by extensive spectroscopic 
analysis. The absolute configurations of 1-3 were determined using 
single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1-3) 
were special amidic isomers. Additionally, all isolated compounds were evaluated 
for their antifungal activity against four phytopathogenic fungi in vitro. 
Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia 
lunata. Liriodenine (5) displayed significant antifungal activity against 
Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is 
obviously better than positive control nystatin, suggesting that it had great 
potential to be developed into an effective and eco-friendly fungicide.

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

DOI: 10.1016/j.fitote.2024.105868
PMID: 38378133 [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.


4. Phytochem Anal. 2023 Dec;34(8):970-983. doi: 10.1002/pca.3265. Epub 2023 Jul
24.

Application of effect-directed analysis using TLC-bioautography for rapid 
isolation and identification of antidiabetic compounds from the leaves of Annona 
cherimola Mill.

Galarce-Bustos O(1), Obregón C(1), Vallejos-Almirall A(2), Folch C(3), Acevedo 
F(4)(5).

Author information:
(1)Laboratorio de Farmacognosia, Facultad de Farmacia, Universidad de 
Concepción, Concepción, Chile.
(2)Grupo Interdisciplinario de Biotecnología Marina (GIBMAR), Centro de 
Biotecnología, Universidad de Concepción, Concepción, Chile.
(3)Departamento de Agroindustrias, Facultad de Ingeniería Agrícola, Universidad 
de Concepción, Chillán, Chile.
(4)Department of Basic Sciences, Faculty of Medicine, Universidad de La 
Frontera, Temuco, Chile.
(5)Center of Excellence translational Medicine, Scientific and Technological 
Bioresource Nucleus, BIOREN, Universidad de La Frontera, Temuco, Chile.

INTRODUCTION: Type 2 diabetes mellitus is a globally prevalent chronic disease 
characterised by hyperglycaemia and oxidative stress. The search for new natural 
bioactive compounds that contribute to controlling this condition and the 
application of analytical methodologies that facilitate rapid detection and 
identification are important challenges for science. Annona cherimola Mill. is 
an important source of aporphine alkaloids with many bioactivities.
OBJECTIVE: The aim of this study is to isolate and identify antidiabetic 
compounds from alkaloid extracts with α-glucosidase and α-amylase inhibitory 
activity from A. cherimola Mill. leaves using an effect-directed analysis by 
thin-layer chromatography (TLC)-bioautography.
METHODOLOGY: Guided fractionation for α-glucosidase and α-amylase inhibitors in 
leaf extracts was done using TLC-bioassays. The micro-preparative TLC was used 
to isolate the active compounds, and the identification was performed by mass 
spectrometry associated with web-based molecular networks. Additionally, in 
vitro estimation of the inhibitory activity and antioxidant capacity was 
performed in the isolated compounds.
RESULTS: Five alkaloids (liriodenine, dicentrinone, N-methylnuciferine, 
anonaine, and moupinamide) and two non-alkaloid compounds 
(3-methoxybenzenepropanoic acid and methylferulate) with inhibitory activity 
were isolated and identified using a combination of simple methodologies. 
Anonaine, moupinamide, and methylferulate showed promising results with an 
outstanding inhibitory activity against both enzymes and antioxidant capacity 
that could contribute to controlling redox imbalance.
CONCLUSIONS: These high-throughput methodologies enabled a rapid isolation and 
identification of seven compounds with potential antidiabetic activity. To our 
knowledge, the estimated inhibitory activity of dicentrinone, 
N-methylnuciferine, and anonaine against α-glucosidase and α-amylase is reported 
here for the first time.

© 2023 John Wiley & Sons, Ltd.

DOI: 10.1002/pca.3265
PMID: 37488746 [Indexed for MEDLINE]


5. Molecules. 2022 Oct 28;27(21):7317. doi: 10.3390/molecules27217317.

Ultra-Large-Scale Screening of Natural Compounds and Free Energy Calculations 
Revealed Potential Inhibitors for the Receptor-Binding Domain (RBD) of 
SARS-CoV-2.

Guo L(1), Zafar F(2), Moeen N(3), Alshabrmi FM(4), Lin J(5), Ali SS(6), Munir 
M(7), Khan A(8)(9), Wei D(7)(8)(9)(10)(11).

Author information:
(1)Zhongjing Chinese Medicine College, Nanyang Institute of Technology, 80 
Changjiang Road, Nanyang 473004, China.
(2)Nishtar Medical University, Multan 59341, Pakistan.
(3)Nawaz Sharif Medical College, Gujrat 50700, Pakistan.
(4)Department of Medical Laboratories, College of Applied Medical Sciences, 
Qassim University, Buraydah 51452, Saudi Arabia.
(5)School of Biology and Biological Engineering, South China University of 
Technology, Guangzhou 510006, China.
(6)Center for Biotechnology and Microbiology, University of Swat, Swat 19120, 
Pakistan.
(7)Division of Biomedical and Life Sciences, Lancaster University, Bailrigg, 
Lancaster LA1 4YW, UK.
(8)Department of Bioinformatics and Biological Statistics, School of Life 
Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, 
China.
(9)Zhongjing Research and Industrialization Institute of Chinese Medicine, 
Zhongguancun Scientific Park, Meixi, Nanyang 473006, China.
(10)Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, 
Nashan District, Shenzhen 518055, China.
(11)State Key Laboratory of Microbial Metabolism, Joint Laboratory of 
International Laboratory of Metabolic and Developmental Sciences, 
Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial 
Resistances, Ministry of Education and School of Life Sciences and 
Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China.

The emergence of immune-evading variants of SARS-CoV-2 further aggravated the 
ongoing pandemic. Despite the deployments of various vaccines, the acquired 
mutations are capable of escaping both natural and vaccine-induced immune 
responses. Therefore, further investigation is needed to design a decisive 
pharmacological treatment that could efficiently block the entry of this virus 
into cells. Hence, the current study used structure-based methods to target the 
RBD of the recombinant variant (Deltacron) of SARS-CoV-2, which was used as a 
model variant. From the virtual drug screenings of various databases, a total of 
four hits were identified as potential lead molecules. Key residues were blocked 
by these molecules with favorable structural dynamic features. The binding free 
energies further validated the potentials of these molecules. The TBE for MNP 
was calculated to be -32.86 ± 0.10 kcal/mol, for SANC00222 the TBE was -23.41 ± 
0.15 kcal/mol, for Liriodenine the TBE was -34.29 ± 0.07 kcal/mol, while for 
Carviolin the TBE was calculated to be -27.67 ± 0.12 kcal/mol. Moreover, each 
complex demonstrated distinct internal motion and a free energy profile, 
indicating a different strategy for the interaction with and inhibition of the 
RBD. In conclusion, the current study demands further in vivo and in vitro 
validation for the possible usage of these compounds as potential drugs against 
SARS-CoV-2 and its variants.

DOI: 10.3390/molecules27217317
PMCID: PMC9656483
PMID: 36364143 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.