Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Nat Prod Res. 2024 Nov 6:1-9. doi: 10.1080/14786419.2024.2425806. Online ahead
 of print.

Tanacetum parthenium and parthenolide increase defensive agents and promote 
antisecretory activity supporting their gastroprotective actions in rodents.

Ferraz CV(1), Steffler AM(1), Dalla Vecchia CA(1), Miorando D(1), Maccagnan 
JC(1), Bohnen LC(1), Simomura VL(1), Von Dentz AL(2), Oss C(2), Pedruzzi T(2), 
Buzatto MV(2), Roman MI(2), Gutiérrez MV(3), Silva LMD(4), Junior WAR(1)(2).

Author information:
(1)Postgraduate Program in Health Sciences, Community University of Chapecó 
Region, Chapecó, Santa Catarina, Brazil.
(2)Laboratory of Pharmacognosy, Community University of the Chapecó Region, 
Chapecó, Santa Catarina, Brazil.
(3)Department of Chemical, Biological and Agricultural Sciences, Universidad de 
Sonora, Navojoa Sonora, Mexico.
(4)Laboratory of TGI Pharmacology and Interactions, Federal University of Santa 
Catarina, Florianópolis, Santa Catarina, Brazil.

Tanacetum parthenium is popularly used to treat gastric disorders. However, the 
gastroprotective activity has not yet been tested. This study evaluated the 
anti-ulcer gastric effects of hydroalcoholic extract from T. parthenium (HETp) 
and parthenolide (PTL), its bioactive compound. Our findings revealed a 
significant reduction in HETp (10, 30, or 100 mg/Kg) and PTL (5 and 50 mg/Kg) in 
ethanol and piroxicam-induced ulcers, and this evidence was corroborated 
histologically. In addition, we explored the acid antisecretory activity by the 
pylorus ligation. Moreover, in mice pre-treated with the inhibitors 
indomethacin, L-NAME, and yohimbine, the antiulcerogenic effects of HETp and PTL 
were abolished, suggesting the involvement of nitric oxide, adrenergic receptors 
and prostaglandins in gastroprotective effects. Additionally, HETp and PTL 
prevented the depletion of SOD and CAT and decreased the activity of MPO and the 
levels of GSH and LPO. The results suggest that gastroprotection of HETp and PTL 
involves different pharmacological pathways.

DOI: 10.1080/14786419.2024.2425806
PMID: 39506519


2. Brain Res. 2024 Oct 29;1847:149304. doi: 10.1016/j.brainres.2024.149304.
Online  ahead of print.

Synergistic interaction between clonidine and ACPA on the modulation of 
anxiety-like behaviors in non-acute restraint stress and acute restraint stress 
conditions.

Chitsaz A(1), Ebrahimi-Ghiri M(2), Zarrindast MR(3), Khakpai F(4).

Author information:
(1)Department of Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, 
Islamic Azad University, Tehran, Iran.
(2)Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, 
Iran.
(3)Department of Pharmacology, School of Medicine, Tehran University of Medical 
Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran 
University of Medical Sciences, Tehran, Iran; Institute for Cognitive Science 
Studies (ICSS), Tehran, Iran.
(4)Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, 
Islamic Azad University, Tehran, Iran; Department of Physiology, Faculty of 
Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 
Electronic address: khakpai@iautmu.ac.ir.

The present research examined the possible role of α-2 adrenergic receptor drugs 
(clonidine, selective α-2 adrenergic receptor agonist, and yohimbine, 
competitive α-2 adrenoreceptor antagonist,) on the effect of 
arachidonylcyclopropylamide (ACPA), a cannabinoid CB1 receptor agonist, in 
non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. The 
animals were unilaterally implanted with a cannula in the left lateral 
ventricle. ARS was carried out by movement restraint at a period of 4 h. An 
elevated plus-maze (EPM) apparatus was used to evaluate anxiety-like behaviors. 
The results indicated that induction of ARS for 4 h induced anxiogenic-like 
behavior due to the reduction of %OAT (the percentage of time spent in the open 
arms) in male mice. Additionally, ARS caused neuronal degeneration in the 
prefrontal cortex. On the other hand, alone intracerebroventricularly (i.c.v.) 
infusions of ACPA (0.5 µg/mouse) and clonidine (0.5 µg/mouse) increased %OAT, 
indicating an anxiolytic-like response in the NARS and ARS mice. In contrast, 
alone i.c.v. infusions of yohimbine (0.5 µg/mouse) decreased %OAT and %OAE (the 
percentage of entries to the open arms), proposing an anxiogenic-like effect in 
the NARS and ARS mice. When the subthreshold dose of ACPA and different doses of 
clonidine were co-injected, ACPA potentiated the anxiolytic-like behavior 
produced by clonidine in the ARS mice. On the other hand, when the ineffective 
dosage of ACPA and different dosages of yohimbine were co-infused, ACPA reversed 
the anxiogenic-like effect induced by yohimbine in the NARS and ARS mice. 
Moreover, the results revealed a synergistic effect between ACPA and clonidine 
upon induction of anxiolytic-like behaviors. It can be concluded that the 
interaction between clonidine and ACPA modulates the anxiety-like behaviors 
induced by stress in male mice.

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

DOI: 10.1016/j.brainres.2024.149304
PMID: 39481745

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. Arch Med Sadowej Kryminol. 2024;74(2):134-146. doi: 
10.4467/16891716AMSIK.24.012.20341.

Fatal poisoning by dietary supplements accompanied by massive rhabdomyolysis and 
multiple organ failure.

[Article in English, Polish; Abstract available in Polish from the publisher]

Fogiel O(1), Rak M(2), Rak M(2), Picheta S(3), Wachholz P(1), Skowronek R(4), 
Sein Anand J(5)(6), Pawlas N(7)(8).

Author information:
(1)Chair and Department of Pharmacology, The Faculty of Medical Sciences in 
Zabrze, Medical University of Silesia, Poland.
(2)Department and Clinic of Emergency Medicine and Disaster Medicine, Academy of 
Silesia, Poland.
(3)The Provincial Specialist Hospital No 5 in Sosnowiec, Poland.
(4)Department of Forensic Medicine and Toxicology, Faculty of Medical Sciences 
in Katowice, Medical University of Silesia, Poland.
(5)Pomeranian Center of Toxicology , Poland.
(6)Division of Clinical Toxicology, Faculty of Health Sciences with the 
Institute of Maritime and Tropical Medicine, Medical University of Gdańsk , 
Poland.
(7)The Provincial Specialist Hospital No 5 in Sosnowiec , Poland.
(8)Chair and Department of Pharmacology, The Faculty of Medical Sciences in 
Zabrze, Medical University of Silesia , Poland.

Obesity epidemic and prevailing standards of desired body shape encourage 
society to use weight loss aids. Thermogenics, which are dietary supplements 
aimed at increasing energy expenditure, are particularly gaining popularity. 
These preparations can be easily purchased without prescription and have a 
complex composition, which means they can interact with numerous substances. The 
article describes the case of a 31-year-old female patient who, in a suicide 
attempt, ingested significant amounts of the dietary supplements 'Blue Magic' 
and 'Purim'. Both supplements contain, among other ingredients: caffeine, 
yohimbine, reserpine, and synephrine. The patient developed multiple organ 
failure, which led to her death on the second day of hospitalization. Poisoning 
by dietary supplements, due to their diverse composition and the lack of 
correlation between the content and the composition declared by the 
manufacturer, can pose a significant threat to the health and life of consumers.

Publisher: Epidemia otyłości oraz obowiązujące wzorce pożądanej sylwetki 
zachęcają wiele osób do sięgania po środki wspomagające odchudzanie. Popularność 
zdobywają przede wszystkim termogeniki, czyli suplementy diety, które mają na 
celu zwiększenie wydatku energetycznego. Preparaty te można łatwo kupić bez 
recepty, mają złożony skład, co powoduje, że mogą wchodzić w liczne interakcje. 
W artykule opisano przypadek 31-letniej pacjentki, która w celu samobójczym 
zażyła znaczną liczbę tabletek suplementu diety „Blue Magic” oraz „Purim”. Oba 
środki zawierają w swoim składzie m.in.: kofeinę, johimbinę, rezerpinę i 
synefrynę. U pacjentki rozwinęła się niewydolność wielonarządowa, która 
doprowadziła do jej zgonu w drugiej dobie hospitalizacji. Zatrucia suplementami 
diety, z powodu ich różnorodnego składu oraz braku korelacji pomiędzy 
zawartością, a deklarowanym przez producenta składem, mogą stanowić duże 
zagrożenie dla zdrowia i życia konsumentów.

Copyright © 2024 by PTMSiK.

DOI: 10.4467/16891716AMSIK.24.012.20341
PMID: 39470758 [Indexed for MEDLINE]


4. Pharmaceuticals (Basel). 2024 Oct 2;17(10):1318. doi: 10.3390/ph17101318.

Exploring the Mechanism of Sempervirine Inhibiting Glioblastoma Invasion Based 
on Network Pharmacology and Bioinformatics.

Zhang B(1), Wang W(2), Song Y(1), Chen H(1), Lin X(1), Chen J(1), Chen Y(1), 
Huang J(3), Li D(1), Wu S(1).

Author information:
(1)College of Pharmacy, Fujian University of Traditional Chinese Medicine, 
Fuzhou 350122, China.
(2)Innovation and Transformation Center, Fujian University of Traditional 
Chinese Medicine, Fuzhou 350122, China.
(3)Fuzhou First General Hospital, Fuzhou 350009, China.

Background: Invasion is an important characteristic of the malignancy of 
glioblastoma (GBM) and a significant prognostic factor. Sempervirine (SPV), a 
yohimbine-type alkaloid, has been proven to inhibit GBM cells proliferation in 
previous research and found to have a potential effect in anti-invasion, but its 
mechanism of anti-invasion is still unknown. Methods: To explore its 
pharmacodynamics in inhibiting GBM cell invasion in this study, we combined 
network pharmacology and bioinformatics to comprehensive exploratory analysis of 
SPV and verified the mechanism in vitro. Results: Firstly, targets of SPV and 
invasion-related genes were collected from public databases. Moreover, GBM 
samples were obtained to analyze differentially expressed genes (DEGs) from The 
Cancer Genome Atlas (TCGA). Then, the relevant targets of SPV inhibiting GBM 
invasion (SIGI) were obtained through the intersection of the three gene sets. 
Further, GO and KEGG analysis showed that the targets of SIGI were heavily 
enriched in the AKT signaling pathway. Subsequently, based on the method of 
machine learning, a clinical prognostic model of the relevant targets of SIGI 
was constructed using GBM samples from TCGA and the Gene Expression Omnibus 
(GEO). A four-genes model (DUSP6, BMP2, MMP2, and MMP13) was successfully 
constructed, and Vina Scores of MMP2 and MMP13 in molecular docking were higher, 
which may be the main targets of SIGI. Then, the effect of SIGI was confirmed 
via functional experiments on invasion, migration, and adhesion assay, and the 
effect involved changes in the expressions of p-AKT, MMP2 and MMP13. Finally, 
combined with AKT activator (SC79) and inhibitor (MK2206), we further confirmed 
that SPV inhibits GBM invasion through AKT phosphorylation. Conclusions: This 
study provides valuable and an expected point of view into the regulation of AKT 
phosphorylation and inhibition of GBM invasion by SPV.

DOI: 10.3390/ph17101318
PMCID: PMC11510114
PMID: 39458959

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


5. Br J Clin Pharmacol. 2024 Oct 21. doi: 10.1111/bcp.16274. Online ahead of
print.

Single-dose and steady-state pharmacokinetics of clomipramine, yohimbine and 
clomipramine/yohimbine combination: A clinical drug-drug interaction study.

Leutzendorff A(1)(2), Al Jalali V(1), Bauer M(1)(3), Minichmayr IK(1), Reiter 
B(4), Duchek MW(1), Nussbaumer-Pröll A(1), Weber M(1), Eberl S(1), Spies M(1), 
Sarhan M(1), Geilen J(1)(5), Walther A(6), Drai D(7), Zeitlinger M(1).

Author information:
(1)Department of Clinical Pharmacology, Medical University of Vienna, Austria.
(2)Department of Medicine I, Division of Infectious Diseases and Tropical 
Medicine, Medical University of Vienna, Austria.
(3)Psychosocial Services in Vienna, Vienna, Austria.
(4)Clinical Department of Medical and Chemical Laboratory Diagnostics, Medical 
University Vienna, Austria.
(5)Clinical Department of Cardiothoracic Vascular Anaesthesia & Intensive Care 
Medicine, Medical University Vienna, Austria.
(6)SEROJAC PME Handels GmbH, Vienna, Austria.
(7)Tel Aviv, Israel.

AIMS: Clomipramine (CLOMI) has shown effectiveness in treating premature 
ejaculation but is linked to erectile dysfunction and reduced libido. Yohimbine 
(YOH), by contrast, is effective in treating erectile dysfunction and may 
improve libido. Combining CLOMI and YOH could potentially leverage the benefits 
of both drugs. This study aimed to investigate the interactions between these 
drugs and to evaluate their safety profile.
METHODS: A prospective, open-labelled, single-centre, pharmacokinetic (PK) 
drug-drug interaction study was performed in 15 healthy male subjects. 
Single-dose and steady-state PK were investigated using noncompartmental 
analysis after mono- and combination therapy of the 2 orally applied drugs. 
Plasma sampling was performed at baseline, 0.5 (YOH), 1, 1.5 (YOH), 2, 3, 4, 5, 
6, 8, 12 and 24 h (CLOMI). Differences in the area under the curve after 
multiple dosing (MD) were determined using an equivalence boundary of 80-125%.
RESULTS: The geometric mean ratio of the area under the curve up to 12 h for MD 
CLOMI (combination vs. monotherapy) was 112% (90% confidence interval: 
104-120%), whereas for MD YOH this ratio was 137% (90% confidence interval: 
112-168%). The study drugs were safe and well tolerated as mono- and combination 
therapy, with no major adverse events reported.
CONCLUSION: A PK assessment of clomipramine and yohimbine indicated a clinically 
significant drug-drug interaction for MD YOH in combination with CLOMI. This 
might be explained by competitive, CLOMI-related inhibition of YOH metabolism, 
probably mediated by cytochrome P450 2D6. However, according to European 
Medicines Agency guidelines, the effect can be classified as interaction absent 
(<1,25 fold) or minor (>1.25-<2-fold). Given the complimentary mechanisms of 
action and the favourable safety profiles, the findings pave the way for future 
efficacy studies.

© 2024 British Pharmacological Society.

DOI: 10.1111/bcp.16274
PMID: 39428980