Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Neurochem. 2024 Nov;168(11):3663-3684. doi: 10.1111/jnc.16191. Epub 2024 Jul
 29.

Supraspinal glycinergic neurotransmission in pain: A scoping review of current 
literature.

Fenech C(1)(2), Winters BL(1)(3), Otsu Y(1)(2), Aubrey KR(1)(2).

Author information:
(1)Pain Management Research Institute, Kolling Institute, Royal North Shore 
Hospital, St Leonards, New South Wales, Australia.
(2)Faculty of Medicine and Health, University of Sydney, Sydney, New South 
Wales, Australia.
(3)Discipline of Pharmacology, School of Pharmacy, Faculty of Medicine and 
Health, University of Sydney, Sydney, New South Wales, Australia.

The neurotransmitter glycine is an agonist at the strychnine-sensitive glycine 
receptors. In addition, it has recently been discovered to act at two new 
receptors, the excitatory glycine receptor and metabotropic glycine receptor. 
Glycine's neurotransmitter roles have been most extensively investigated in the 
spinal cord, where it is known to play essential roles in pain, itch, and motor 
function. In contrast, less is known about supraspinal glycinergic functions, 
and their contributions to pain circuits are largely unrecognized. As 
glycinergic neurons are absent from cortical regions, a clearer understanding of 
how supraspinal glycine modulates pain could reveal new pharmacological targets. 
This review aims to synthesize the published research on glycine's role in the 
adult brain, highlighting regions where glycine signaling may modulate pain 
responses. This was achieved through a scoping review methodology identifying 
several key regions of supraspinal pain circuitry where glycine signaling is 
involved. Therefore, this review unveils critical research gaps for supraspinal 
glycine's potential roles in pain and pain-associated responses, encouraging 
researchers to consider glycinergic neurotransmission more widely when 
investigating neural mechanisms of pain.

© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons 
Ltd on behalf of International Society for Neurochemistry.

DOI: 10.1111/jnc.16191
PMID: 39075923 [Indexed for MEDLINE]


2. Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul 23. doi: 
10.1007/s00210-024-03299-x. Online ahead of print.

Antiepileptic profile of Parawixin-11, purified from Parawixia bistriata spider 
venom (Araneae, Araneidae), in Wistar rats.

Pereira AC(1)(2), Cunha AOS(1)(2), Mortari MR(1)(3), Fachim HA(1)(2), Campos 
GAA(3), Lopes NP(4), Dos Santos WF(5)(6).

Author information:
(1)Neurobiology and Venoms Laboratory, Department of Biology, College of 
Philosophy, Sciences and Literature (FFCLRP), University of São Paulo (USP), Av. 
Bandeirantes, 3900, Ribeirão Preto, São Paulo, CEP: 14040-090, Brazil.
(2)Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, São Paulo, 
Brazil.
(3)Laboratory of Neuropharmacology, Department of Physiological Sciences, 
University of Brasilia (UnB), Brasilia, DF, Brazil.
(4)Organic Chemistry Laboratory, Department of Physics and Chemistry, Ribeirão 
Preto School of Pharmacy (FCFRP), University of São Paulo (USP), Ribeirão Preto, 
São Paulo, Brazil.
(5)Neurobiology and Venoms Laboratory, Department of Biology, College of 
Philosophy, Sciences and Literature (FFCLRP), University of São Paulo (USP), Av. 
Bandeirantes, 3900, Ribeirão Preto, São Paulo, CEP: 14040-090, Brazil. 
wagnerf@usp.br.
(6)Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, São Paulo, 
Brazil. wagnerf@usp.br.

The pharmacological treatment of epilepsy is often complex due to the lack of 
efficacy in many patients and profound side effects from current drugs, 
including sedation, motor impairment, and teratogenesis. In the quest for new 
antiepileptic drugs, animal venoms offer a valuable source of neuroactive 
molecules targeting ion channels and neurotransmitter receptors. This study 
investigates the antiepileptic potential of compounds isolated from the venom of 
the Parawixia bistriata spider. One compound, designated Parawixin-11, 
demonstrated significant anticonvulsant effects when injected into the cerebral 
ventricle in a dose-response manner. It effectively countered seizures induced 
by bicuculline (ED50 0.16 µg/animal), pentylenetetrazole (ED50 0.08 µg/animal), 
strychnine (ED50 0.05 µg/animal), pilocarpine (ED50 0.10 µg/animal), and NMDA 
(ED50 0.008 µg/animal). We also assessed whether intracerebroventricular 
administration of Parawixin-11 caused motor or cognitive impairments in rats 
using the open field, rotarod, and Morris water maze tests. No differences in 
exploration or movement were observed with doses of 0.3, 0.2, or 0.1 µg of 
Parawixin-11. Although there was an increased latency to find the platform 
during the acquisition phase of the Morris water maze test, no differences in 
spatial memory retention were noted. Given Parawixin-11's potency against 
NMDA-induced seizures, we hypothesize that it may modulate the glutamatergic 
system, aligning with the mechanisms of several spider-derived polyamines.

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

DOI: 10.1007/s00210-024-03299-x
PMID: 39042155


3. J Biomater Appl. 2024 Oct;39(4):317-331. doi: 10.1177/08853282241258161. Epub 
2024 Jul 20.

Preparation, characterization, and liver targeting evaluation of a novel 
sustained-release brucine self-assembled micelle mediated by glycyrrhetinic 
acid.

Guan Q(1), Yang H(1), Xia Z(1), Li X(1), Zhang Y(1), Lin Z(1), Sun S(1), Yang 
Z(1), Zhou X(1), Lv S(1), Wang Y(1).

Author information:
(1)Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang 
University of Chinese Medicine, Ministry of Education, 24 Heping Road, Xiangfang 
District, Harbin, Heilongjiang Province, China.

Background: Cancer is a serious threat to human life, health and social 
development. In recent years, nanomicelles, as an emerging drug carrier 
material, have gradually entered people's field of vision because of their 
advantages of improving bioavailability, maintaining drug levels, reducing 
systemic side effects and increasing drug accumulation at target sites. Methods: 
In this study, B-GPSG nano-micelles were prepared by film dispersion hydration 
method using brucine as model drug and glycyrrhetinic acid-polyethylene 
glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer 
as nano-carrier. The preparation process, characterization, drug release in 
vitro, pharmacokinetics and liver targeting were investigated. Results: The 
results showed that the range of particle size, polydispersion index and Zeta 
potential were 102.7 ± 1.09 nm, 0.201 ± 0.02 and -24.5 ± 0.19 mV respectively. 
The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, 
respectively. The drug release experiments in vitro and pharmacokinetic 
experiments showed that it had obvious sustained release effect. For 
pharmacokinetics study, it shows that both the B-GPSG solution group and the 
B-PSG solution group changed the metabolic kinetic parameters of brucine, but 
the B-GPSG solution group had a better effect. Compared with the B-PSG solution 
group, the drug was more prolonged in rats. The half-life in the body and the 
retention time in the body of B-GPSG are more helpful to improve the 
bioavailability of the drug and play a long-term effect. The tail vein injection 
results of mice indicate that B-GPSG can target and accumulate brucine in the 
liver without affecting other key organs. Cell uptake experiments and tissue 
distribution experiments in vivo show that glycyrrhetinic acid modified 
nano-micelles can increase the accumulation of brucine in hepatocytes, has a 
good liver targeting effect, and can be used as a new preparation for the 
treatment of liver cancer. Conclusion: The B-SPSG prepared in this experiment 
can provide a new treatment method and research idea for the treatment of liver 
cancer.

DOI: 10.1177/08853282241258161
PMID: 39031074 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of conflicting interestsThe 
author(s) declared no potential conflicts of interest with respect to the 
research, authorship, and/or publication of this article.


4. PhytoKeys. 2024 Jun 24;243:137-148. doi: 10.3897/phytokeys.243.123921. 
eCollection 2024.

Clarifying the nomenclature of Strychnosbredemeyeri and Lasiostoma 
(Loganiaceae).

Setubal RB(1)(2), Struwe L(3), Prado J(4), Forzza RC(1)(2)(5).

Author information:
(1)Departamento de Botânica, Instituto de Biociências, Universidade de São 
Paulo, Rua do Matão, 277, 05508-090, São Paulo, SP, Brazil.
(2)Jardim Botânico do Rio de Janeiro, Rua Pacheco Leão, 915, 22460-030, Rio de 
Janeiro, RJ, Brazil.
(3)Department of Ecology, Evolution, and Natural Resources, Rutgers University, 
14 College Farm Road, New Brunswick, NJ 08901, USA.
(4)Department of Plant Biology, Rutgers University, 59 Dudley Road, New 
Brunswick, NJ 08901, USA.
(5)Instituto de Pesquisas Ambientais (IPA), Herbário SP, Av. Miguel Estéfano, 
3687, CEP 04301-012, São Paulo, SP, Brazil.

Strychnos (Loganiaceae, Gentianales) is a large and pantropical genus of woody 
plants, ethnobotanically important as a source of many toxic alkaloids, 
including strychnine. Unfortunately, the status of numerous names at various 
ranks of Strychnos remains unresolved, including that of many specific or 
infraspecific taxa in the Neotropics. In this study, we address 
Strychnosbredemeyeri (basionym Lasiostomabredemeyeri), a species described in 
1827 based on type material collected in Venezuela during the poorly documented 
Austrian Märter expedition (1783-1788). Strychnosbredemeyeri is an unarmed liana 
with solitary tendrils and axillary inflorescences that occurs in Neotropical 
rainforests and savannas in Brazil, Guyana, Trinidad and Tobago, and Venezuela. 
We clarify here the nomenclatural status of Lasiostoma Schreb., an illegitimate 
and superfluous genus currently in synonymy under Strychnos, and its former 
species Lasiostomabredemeyeri [= Strychnosbredemeyeri]. Also, we lectotypify 
S.pedunculata and S.trinitensis, both taxa currently synonyms of S.bredemeyeri.

Robberson Bernal Setubal, Lena Struwe, Jefferson Prado, Rafaela Campostrini 
Forzza.

DOI: 10.3897/phytokeys.243.123921
PMCID: PMC11217646
PMID: 38957681

Conflict of interest statement: The authors have declared that no competing 
interests exist.


5. Cell Biochem Biophys. 2024 Sep;82(3):2373-2385. doi:
10.1007/s12013-024-01348-z.  Epub 2024 Jun 14.

Brucine Suppresses Malignant Progression of Prostate Cancer by Decreasing 
Sarcosine Accumulation via Downregulation of GNMT in the Glycine/sarcosine 
Metabolic Pathway.

Miao L(#)(1), Liu Y(#)(2), Chen W(1), Gao C(1), Zhang Y(1), Wei J(1), Cao X(3).

Author information:
(1)Department of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou 
Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China.
(2)Department of Hematology, The Affiliated Hospital of Xuzhou Medical 
University, Xuzhou, 221004, PR China.
(3)Department of Urology, Xuzhou No. 1 People's Hospital, the Affiliated Xuzhou 
Municipal Hospital of Xuzhou Medical University, Xuzhou, 221004, PR China. 
caoxiliang1971@sina.com.
(#)Contributed equally

Prostate cancer (PCa) remains a leading cause of cancer-related incidence and 
mortality in men. Disruptions in amino acid (AA) metabolism contribute to the 
disease progression, with brucine, a glycine antagonist, exhibiting antitumor 
effects. This study explores the antitumor impact of brucine on PCa and 
investigates its mechanisms in regulating AA metabolic pathways. The study 
employed the PCa cell line DU-145, characterized by high sarcosine (Sar) levels, 
for various assays including Cell Counting Kit-8 (CCK8), wound healing, 
Transwell, 5-Ethynyl-2'-deoxyuridine (EDU), TdT mediated dUTP Nick End Labeling 
(TUNEL), flow cytometry, Western blot, and ultra-high-performance liquid 
chromatography-tandem mass spectrometry (UPLC-MS/MS). Network pharmacological 
analysis determined the anticancer mechanisms of brucine. Sar levels in DU-145 
cells were significantly higher than in normal prostatic epithelial cells 
RWPE-1. Treatment with brucine resulted in a marked decrease in cell viability, 
proliferation, invasion, and migration, while promoting apoptosis in a 
dose-dependent manner. Sar levels decreased with increasing brucine 
concentration. Network pharmacology analysis linked brucine's anticancer effect 
to the AA metabolism and glycine N-methyltransferase (GNMT) pathways. GNMT 
expression in prostate cancer tissues and The Cancer Genome Atlas database was 
significantly elevated compared to controls. Treatment with brucine led to 
downregulation of GNMT expression in DU-145 cells without significant effect on 
sarcosine dehydrogenase (SARDH). Addition of recombinant GNMT partially reversed 
the inhibitory effects of brucine on DU-145 cells. Treatment with brucine 
downregulates GNMT expression in DU-145 cells, reducing Sar accumulation and 
inhibiting tumor progression. These findings provide new insights into the 
antitumor mechanisms of brucine in PCa.

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

DOI: 10.1007/s12013-024-01348-z
PMID: 38877335 [Indexed for MEDLINE]