Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Vet World. 2024 Sep;17(9):1972-1982. doi: 10.14202/vetworld.2024.1972-1982.
Epub  2024 Sep 1.

Neuroprotective effects of Paederia foetida Linn. on scopolamine-induced 
cognitive impairment in rats.

Pakaprot N(1), Khamphaya T(2), Kwankaew P(3), Ninsuwan S(3), Laisunthad S(3), 
Thonoi K(3), Kuraeiad S(3)(4).

Author information:
(1)Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol 
University, Srisavarindhira Bldg., 13 Floor, Wanglang Road, Siriraj Subdistrict, 
Bangkoknoi District, Bangkok, 10700, Thailand.
(2)Department of Occupational Health and Safety, School of Public Health, 
Walailak University, Nakhon Si Thammarat, 80160, Thailand.
(3)Department of Medical Technology, School of Allied Health Sciences, Walailak 
University, Nakhon Si Thammarat, 80160, Thailand.
(4)Research Center in Tropical Pathobiology, Walailak University, Nakhon Si 
Thammarat, 80160, Thailand.

BACKGROUND AND AIM: Alzheimer's disease (AD) poses a significant health-care 
challenge, often linked to cognitive decline caused by oxidative stress. This 
study investigated the potential neuroprotective effects of the Paederia foetida 
leaf extract (PFE) in rats that exhibited scopolamine-induced dementia mimicking 
AD.
MATERIALS AND METHODS: Forty-two male rats were treated with either donepezil 
(0.5 mg/kg) or PFE at doses of 250, 500, and 1000 mg/kg for 14 days before and 
14 days after the beginning of Alzheimer's-like symptoms after 14 consecutive 
days of scopolamine administration. Behavioral tests, including the open-field 
test for locomotor activity and the Morris water maze task for learning and 
memory assessment, were conducted. Neuronal cell counts and biochemical assays 
were performed to further analyze outcomes.
RESULTS: All groups exhibited normal locomotor activity. The scopolamine group 
displayed longer escape latency times, reduced time in the target quadrant, 
decreased number of surviving neurons, and increased malondialdehyde and 
decreased glutathione levels compared with the control group. However, 
pre-treatment with 1000 mg/kg PFE notably mitigated the neurotoxic effects of 
scopolamine.
CONCLUSION: The neuroprotective properties of PFE are highlighted, suggesting 
its potential as a promising treatment strategy for AD.

Copyright: © Pakaprot, et al.

DOI: 10.14202/vetworld.2024.1972-1982
PMCID: PMC11536741
PMID: 39507784

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


2. Heliyon. 2024 Oct 17;10(20):e39483. doi: 10.1016/j.heliyon.2024.e39483. 
eCollection 2024 Oct 30.

Antiepileptic and anti-inflammatory effects of Lippia multiflora moldenke 
(Verbenaceae) in mice model of chronic temporal lobe epilepsy induced by 
pilocarpine.

Ngaibi J(1), Bigued(2), Kandeda AK(3), Nguezeye Y(4)(5), Wangbara TA(2), Gaoudji 
L(5), Taiwe GS(6), Bum EN(2)(5).

Author information:
(1)Department of Animal Biology, Faculty of Science, University of Dschang, 
Cameroon, P.O. Box 67, Dschang, Cameroon.
(2)Department of Biological Sciences, Faculty of Science, University of Maroua, 
P.O. Box 814, Maroua, Cameroon.
(3)Department of Animal Biology and Physiology, Faculty of Science, University 
of Yaounde 1, P.O. Box, Yaounde, Cameroon.
(4)Centre for Research on Medicinal Plants and Traditional Medicine, Institute 
of Medical Research and Medicinal Plants Studies, Yaoundé, Cameroon.
(5)Department of Biological Sciences, Faculty of Science, University of 
Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon.
(6)Department of Animal Biology and Conservation, Faculty of Science, University 
of Buea, Cameroon, P.O. Box 63, Buea, Cameroon.

Lippia multiflora Moldenke (Verbenaceae) is an aromatic plant used as a popular 
medicine with antidepressant, antispasmodic, antifungal, anti-inflammatory, and 
antioxidant properties. In this study, we explored the effects of L. multiflora 
in mice chronic model of temporal lobe epilepsy induced by pilocarpine and 
kindled with pentylenetetrazol. Mice were divided into 7 groups of 10 animals, 
and received a single dose of pilocarpine (360 mg/kg, i.p.), 20 min after the 
administration of N-methyl-scopolamine (1 mg/kg, i.p). Thirty days after the 
induction of status epilepticus, animals were daily treated for 60 days with 
distilled water (10 mL/kg, per os) for the negative control group, extract 
(23.07, 57.69, 115.39 and 230.78 mg/kg, per os) for the test groups, and sodium 
valproate (300 mg/kg, i.p) for the positive control group. On every 10th day, 
animals were injected with a sub-convulsive dose of pentylenetetrazol (15 mg/kg, 
i.p) 1 h after the administration of the various treatments to assess the 
susceptibility of animals to seizures. At the end of behavioural tests, animals 
were sacrificed and the level of inflammatory cytokines was assessed in the 
hippocampus. The plant extract reduced (p < 0.001) the occurrence of seizures 
and the number of spontaneous recurrent seizures induced by pilocarpine in mice. 
It ameliorated the levels of inflammatory cytokines (TNF-α, INF- γ, IL-1β, IL-6, 
and IL-10) in the hippocampus. The in vitro studies show that L. multiflora have 
a high amount of total phenolic content, flavonoids and tannins and also have 
some good antioxidant properties. These results suggest that L. multiflora 
aqueous extracts has the potential to be a promising complementary and 
alternative medicine for the treatment of epilepsy, due to its antiepileptic, 
anti-inflammatory and antioxidant effects.

DOI: 10.1016/j.heliyon.2024.e39483
PMCID: PMC11533593
PMID: 39498072

Conflict of interest statement: 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. Mol Neurobiol. 2024 Nov 4. doi: 10.1007/s12035-024-04573-y. Online ahead of 
print.

Analysis of Differential microRNA Expression in the Hippocampus of 
Scopolamine-Induced Amnesic Mouse Model.

Verma S(1), Sivanandam TM(2).

Author information:
(1)Biochemistry and Molecular Biology Laboratory, Department of Zoology, 
Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
(2)Biochemistry and Molecular Biology Laboratory, Department of Zoology, 
Institute of Science, Banaras Hindu University, Varanasi, 221005, India. 
stmani@bhu.ac.in.

Amnesia is characterized by memory deficits linked to various neurodegenerative 
pathologies and can be induced by the administration of scopolamine, a 
cholinergic antagonist. Scopolamine-induced amnesia is a well-studied 
pharmacological animal model that simulates memory impairment caused by aging, 
brain illnesses, neuropathologies, and trauma. However, the molecular mechanism 
of amnesia, more importantly in terms of microRNA (miRNA) regulation, is not 
well understood. Therefore, this study aimed to analyze miRNA profiles in the 
hippocampus of both control mice and those treated with scopolamine (amnesic 
mice). Initially, a short cDNA library was prepared for each sample and then 
sequenced on the Illumina platform. Among the total differentially expressed 
miRNAs, 113 were significantly upregulated and 96 were downregulated in the 
scopolamine group in comparison to the control group. Ten upregulated and ten 
downregulated miRNAs were validated to confirm the reliability of the sequencing 
results using qRT-PCR (quantitative real-time PCR). Furthermore, we performed a 
target prediction analysis intersecting the results from TargetScan, miRDB 
(miRNA database), and Miranda to analyze the targets of the dysregulated miRNAs. 
We also conducted a pathway analysis to investigate the molecular, cellular, and 
biological functions of these targets. miRNA‒target interactions were found to 
play roles in various signaling pathways during amnesia. These results provide 
an initial insight for the contribution of miRNAs to scopolamine-induced 
amnesia, as well as their possible application as markers of disease pathology.

© 2024. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s12035-024-04573-y
PMID: 39495226


4. Neuroscience. 2024 Nov 1:S0306-4522(24)00577-3. doi: 
10.1016/j.neuroscience.2024.10.054. Online ahead of print.

Neuroprotective properties of a thiazolidine-2,4-dione derivative as an 
inhibitory agent against memory impairment and phosphorylated tau: In vitro and 
in vivo investigations.

Taheri M(1), Moradi MH(1), Koraee Y(1), Moghadam FH(2), Ershad Nedaei S(3), 
Veisi M(3), Ghafouri H(4).

Author information:
(1)Department of Biology, Faculty of Basic Sciences, University of Guilan, 
Rasht, Iran.
(2)Department of Animal Biotechnology, Cell Science Research Center, Royan 
Institute for Biotechnology, ACECR, Isfahan, Iran.
(3)Department of Physiology, School of Medicine, Kermanshah University of 
Medical Sciences, Kermanshah, Iran.
(4)Department of Biology, Faculty of Basic Sciences, University of Guilan, 
Rasht, Iran. Electronic address: h.ghafoori@guilan.ac.ir.

Alzheimer's disease (AD) is the most common form of neurodegeneration that 
results in memory disorders and cognitive impairment. The present study 
investigated the neuroprotective effects of the synthesized 
thiazolidine-2,4-dione derivative, 
(E)-5-(4-chlorobenzylidene)-3-(2-oxo-2-phenylethyl)thiazolidine-2,4-dione 
(TZ4C), an inhibitor of p-Tau and memory impairment, using a SH-SY5Y cell model 
of methamphetamine-induced tauopathy and a scopolamine-induced memory impairment 
model in Wistar rats. In the present study, the neuroprotective effect of TZ4C 
was studied in a SH-SY5Y cellular model of methamphetamine-induced (2 mM) 
tauopathy and a scopolamine-induced (1.5 mg/kg/day) memory impairment model in 
male Wistar rats (n = 48). The memory functions and learning abilities of the 
rats were evaluated using the Morris water maze (MWM) and passive avoidance 
tests. Additionally, AChE activity in the rat hippocampus was quantified, and 
the expression of p-Tau, HSP70, and caspase-3 in both in vitro and in vivo 
samples was evaluated through Western blot analysis. TZ4C (0.1-1000 µM) did not 
exhibit significantly toxic effects on SH-SY5Y cell viability. Western blot 
results indicated that TZ4C led to reduced expression of p-Tau, HSP70, and 
cleaved caspase-3 in SH-SY5Y cells (3 and 10 µM) and the rat hippocampus (2 and 
4 mg/kg). Additionally, the findings suggested that TZ4C enhanced memory 
function in rats with scopolamine-induced impairment and decreased 
acetylcholinesterase (AChE) specific activity. The comprehensive analysis of in 
vitro and in vivo experiments underscores the neuroprotective potential 
(improved neuropathology and reduced memory impairment) of TZ4C. These findings 
highlight the promise of TZ4C as a candidate for drug discovery programs to 
identify effective therapies for AD.

Copyright © 2024 International Brain Research Organization (IBRO). Published by 
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuroscience.2024.10.054
PMID: 39489476

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.


5. Theranostics. 2024 Oct 14;14(17):6708-6725. doi: 10.7150/thno.100986. 
eCollection 2024.

Intracalvariosseous administration of donepezil microspheres protects against 
cognitive impairment by virtue of long-lasting brain exposure in mice.

Kang JH(1), Yang JK(2), Cho KH(1), Lee OH(1), Kwon H(3), Kim SY(1), Kim S(3)(4), 
Ko YT(1).

Author information:
(1)College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon 
University, Incheon, 21936, Republic of Korea.
(2)Department of Chemical Engineering, Dong-Eui University, Busan, 47340, 
Republic of Korea.
(3)Chemical & Biological Integrative Research Center, Korea Institute of Science 
and Technology, Seoul, 02792, Republic of Korea.
(4)KU-KIST Graduate School of Converging Science and Technology, Korea 
University, Seoul, 02841, Republic of Korea.

Rationale: Recent studies have demonstrated the direct connections between the 
skull bone marrow, meninges, and brain. In an effort to explore these 
connections for the purpose of brain drug delivery, we previously proposed the 
direct application of CNS drugs into the diploic space between the outer and 
inner cortex of the skull, namely, intracalvariosseous administration (ICO). It 
was successfully demonstrated that small molecular to large colloidal drugs can 
readily reach the brain after ICO in mice and rabbits. Here, we report that a 
single ICO of donepezil microspheres protects cognitive impairment in Alzheimer 
mouse models over a month-long period. Methods: Donepezil-loaded long-acting 
microspheres (DPZ@LAM) were prepared with biodegradable 
poly(DL-lactide-co-glycolide) (PLGA). Pharmacokinetic study and behavioral test 
were performed to determine the brain exposure and therapeutic effects after ICO 
of DPZ@LAM in scopolamine-induced memory-deficient mice. Results: DPZ@LAM were 
capable of a month-long and precisely controlled drug release. After a single 
ICO of DPZ@LAM, DPZ concentration in brain sustained above the effective 
therapeutic levels for four weeks. The long-lasting brain exposure also led to 
significantly recovered cognitive function in scopolamine-induced 
memory-deficient mice, along with decreased acetylcholinesterase activity and 
increased brain-derived neurotrophic factor. Conclusions: ICO allows for 
BBB-bypassing brain drug delivery through the direct connection between the 
skull bone marrow and brain, providing an alternative approach for the treatment 
of neurodegenerative diseases with otherwise BBB impermeable CNS drugs.

© The author(s).

DOI: 10.7150/thno.100986
PMCID: PMC11519799
PMID: 39479440 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have declared 
that no competing interest exists.