Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. RSC Med Chem. 2024 Oct 24. doi: 10.1039/d4md00495g. Online ahead of print.

Synthesis, in silico and bio-evaluation studies of new isothiocyanate 
derivatives with respect to COX inhibition and H(2)S release profiles.

Yilmaz YB(1), Güngör T(2), Dönmez S(1), Atalay HN(1), Siyah P(3), Durdağı 
S(4)(5)(6), Ay M(2), Boyunegmez Tumer T(7).

Author information:
(1)Graduate Program of Molecular Biology and Genetics, School of Graduate 
Studies, Canakkale Onsekiz Mart University Canakkale Türkiye.
(2)Natural Products and Drug Research Laboratory, Department of Chemistry, 
Faculty of Science, Canakkale Onsekiz Mart University Canakkale Türkiye 
tgungor@comu.edu.tr mehmetay06@comu.edu.tr.
(3)Department of Biochemistry, School of Pharmacy, Bahçeşehir University 
Istanbul Türkiye.
(4)Computational Biology and Molecular Simulations Laboratory, Department of 
Biophysics, School of Medicine, Bahçeşehir University Istanbul Türkiye.
(5)Molecular Therapy Lab, Department of Pharmaceutical Chemistry, School of 
Pharmacy, Bahçeşehir University Istanbul Türkiye.
(6)Lab for Innovative Drugs (Lab4IND), Computational Drug Design Center 
(HITMER), Bahçeşehir University Istanbul Türkiye.
(7)Department of Molecular Biology and Genetics, Faculty of Science, Canakkale 
Onsekiz Mart University Canakkale Türkiye tumertb@comu.edu.tr.

The development of H2S-donating derivatives of non-steroidal anti-inflammatory 
drugs (NSAIDs) is considered important to reduce or overcome their 
gastrointestinal side effects. Sulforaphane, one of the most extensively studied 
isothiocyanates (ITCs), effectively releases H2S at a slow rate. Thus, we 
rationally designed, synthesized, and characterized new ITC derivatives (I1-3 
and I1a-e) inspired by the natural compound sulforaphane. The anti-inflammatory 
properties of these compounds were evaluated by their inhibitory activities 
against cyclooxygenase targets COX-1 and COX-2. Additionally, the cytotoxicity 
of the compounds was tested using the MTT assay on LPS-induced RAW 264.7 cells, 
revealing no cytotoxic effects at low doses. Notably, compounds I1 and 
fluorine-containing ester derivative I1c emerged as the most potent and 
selective COX-2 inhibitors, with selectivity indexes of 2611.5 and 2582.4, 
respectively. The H2S-releasing capacities of ITC derivatives were investigated 
and compared with that of sulforaphane, showing that while compounds I1-3 
exhibit slow and similar H2S release to sulforaphane, the release from compounds 
I1a-e was not as pronounced as that of the standard. Physics-based molecular 
modeling studies including molecular docking and molecular dynamics (MD) 
simulations, binding free energy calculations and absorption, distribution, 
metabolism, and excretion (ADME) analyses were also conducted. MD simulations 
analysis underscored the crucial amino acids such as Tyr385, Trp387, Phe518, 
Val523, and Ser530 in the interactions between I1c hit compound and COX-2. The 
combined in silico and in vitro findings suggest that compounds I1 and I1c are 
promising NSAID candidates against selective COX-2 inhibition.

This journal is © The Royal Society of Chemistry.

DOI: 10.1039/d4md00495g
PMCID: PMC11536671
PMID: 39507615

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


2. J Sep Sci. 2024 Nov;47(21):e202400366. doi: 10.1002/jssc.202400366.

Rapid Identification of Chemical Constituents of Sanhua Decoction in Vivo and in 
Vitro and the Metabolites of Rhubarb Anthraquinone Aglycone by Ultra-High 
Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem 
Mass Spectrometry.

Wang X(1)(2)(3)(4), Ma J(1)(2)(3)(4), Qian Q(1)(2)(3)(4), Gao L(1)(2)(3)(4), 
Zhen Y(1)(2)(3)(4), Tian Y(1)(2)(3)(4), Niu L(1)(2)(3)(4), Wang X(1)(2)(3)(4).

Author information:
(1)School of Integrated Traditional Chinese and Western Medicine, Hebei 
University of Chinese Medicine, Shijiazhuang, P. R. China.
(2)Hebei Traditional Chinese Medicine Formula Granule Engineering and Technology 
Innovate Center, Hebei University of Chinese Medicine, Shijiazhuang, P. R. 
China.
(3)Quality Evaluation and Standardization Hebei Province Engineering Research 
Center of Traditional Chinese Medicine, Hebei University of Chinese Medicine, 
Shijiazhuang, P. R. China.
(4)TCM Formula Granule Research Center of Hebei Province University, Hebei 
University of Chinese Medicine, Shijiazhuang, P. R. China.

Sanhua Decoction (SHD) is a classic prescription for the treatment of stroke in 
the clinic. Based on the combination strategy in vitro and in vivo, the chemical 
constituents of SHD were characterized by ultra-high-performance liquid 
chromatography coupled with quadrupole time-of-flight tandem mass spectrometry, 
and the metabolites of five effective anthraquinone aglycones (emodin, 
chrysophanol, rhein, aloe-emodin, and physcion) of rhubarb in SHD were studied. 
A total of 222 compounds were isolated and identified in vitro, including 50 
flavonoids and their glycosides, 41 coumarins, 22 anthraquinones, 22 tannins, 14 
phenylpropanoids, 16 alkaloids, 18 organic acids and their esters, 14 lignans, 
six anthrones, and 19 other compounds. A total of 111 prototype components were 
isolated and identified in vivo. Among them, 26, 82, 101, and 46 prototype 
components and 87 metabolites were detected in plasma, urine, feces, and bile 
for the first time. This study provides a basis for the identification of 
chemical components in vivo and in vitro and the analysis of potential 
pharmacodynamic components of SHD, and provides a basis for further study of 
pharmacodynamic mechanism.

© 2024 Wiley‐VCH GmbH.

DOI: 10.1002/jssc.202400366
PMID: 39503378 [Indexed for MEDLINE]


3. Drug Des Devel Ther. 2024 Oct 31;18:4859-4875. doi: 10.2147/DDDT.S475838. 
eCollection 2024.

Integrated Metabolomics and Network Pharmacology Study on the Mechanism of 
Rehmanniae radix Extract for Treating Thrombosis.

Du H(1)(2)(3), Zhang S(1), Yuan K(4), Yang Z(5), Wu M(4).

Author information:
(1)Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 
Sichuan, People's Republic of China.
(2)Department of Pharmacy, Sichuan Public Health Clinical Center, Chengdu, 
Sichuan, People's Republic of China.
(3)State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy 
School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 
People's Republic of China.
(4)Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, 
People's Republic of China.
(5)Department of Nuclear Medicine, Chengdu Second People's Hospital, Chengdu, 
Sichuan, People's Republic of China.

BACKGROUND: Rehmanniae Radix (RR) has received attention for its antithrombotic 
effect. However, few studies have independently explored the bioactive 
components responsible for its antithrombotic bioactivity and the potential 
mechanism. We aimed to reveal the antithrombotic mechanisms of RR by using 
metabolomics integrated with network pharmacology.
METHODS: A thrombosis model was established by intraperitoneal injection of type 
I carrageenan in rats, and antithrombotic function was evaluated at different 
doses of RR. Metabolomics was used to identify the differential metabolites in 
the serum. Network pharmacology was then applied to identify the potential 
targets for the antithrombotic activity of the RR. An integrated network of 
metabolomics and network pharmacology was constructed using Cytoscape. Finally, 
key targets were verified using molecular docking.
RESULTS: RR at 5.4 g/kg significantly alleviated the thrombosis. Thirteen 
potentially significant metabolites were involved in the therapeutic effects of 
RR against thrombosis, most of which were regulated for recovery after RR 
treatment. An integrated analysis of metabolomics and network pharmacology 
showed that the antithrombosis effect of RR was closely associated with the 
regulation of PLA2G2A, PTGS1, ALOX5, and CYP2C9. Molecular docking showed high 
affinity between the key targets and components of RR. We speculated that the 
components of RR, such as catalpol, ferulic acid methyl ester, and methyl 
4-hydroxycinnamate, might act on key proteins, including PLA2G2A, PTGS1, and 
ALOX5, to exert antithrombosis effects.
CONCLUSION: This study confirmed the antithrombotic effect of high-dose RR, 
revealed the antithrombotic mechanism and potential material basis, and laid the 
foundation for the antithrombotic clinical application of RR. Furthermore, it 
provides a successful case reference for screening natural herbal components and 
exploring their potential pharmacological mechanisms.

© 2024 Du et al.

DOI: 10.2147/DDDT.S475838
PMCID: PMC11533886
PMID: 39497835 [Indexed for MEDLINE]

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


4. Food Sci Biotechnol. 2024 Jun 17;33(15):3501-3513. doi: 
10.1007/s10068-024-01591-3. eCollection 2024 Dec.

Succession of microbial community structure in fermented grains during the 
fermentation of strong-flavor Baijiu and its impact on the metabolism of acids, 
alcohols, and esters.

Huang Z(1)(2), Zeng B(1)(2), Deng J(1)(2), Ren Z(1)(2), Xie J(1)(2), Wei 
C(1)(2).

Author information:
(1)Sichuan University of Science & Engineering, Liquor Brewing Biotechnology and 
Application Key Laboratory of Sichuan Province, Yibin, 644000 China.
(2)Liquor Brewing Biotechnology and Intelligent Manufacturing Key Laboratory of 
China Light Industry, Yibin, 644000 China.

The study clarified the succession of microbial community structures in 
fermented grains (FG) and their association with flavor compounds, along with 
their potential metabolic functions. The community diversity, functional genera 
and metabolites in FG were investigated by polyphasic detecting approaches. 
There are 13 dominant microorganisms in FG (relative abundance > 1%). Moisture 
and acidity are the key indicators driving the succession of microbial 
communities in FG. Eight kinds of microorganisms were involved in the metabolism 
of acid, higher alcohols and ethanol in FG and the abundance of pyruvate 
dehydrogenase and lactate dehydrogenase were significantly higher than other 
enzymes (P < 0.05). The results showed that 23 main flavor compounds were the 
results of the interaction of dominant microorganisms in FG. This study provides 
a basis for the formation of flavor substances in strong-flavor Baijiu.

© The Korean Society of Food Science and Technology 2024. Springer Nature or its 
licensor (e.g. a society or other partner) holds exclusive rights to this 
article under a publishing agreement with the author(s) or other 
rightsholder(s); author self-archiving of the accepted manuscript version of 
this article is solely governed by the terms of such publishing agreement and 
applicable law.

DOI: 10.1007/s10068-024-01591-3
PMCID: PMC11525368
PMID: 39493398

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


5. Toxicon. 2024 Oct 26:108152. doi: 10.1016/j.toxicon.2024.108152. Online ahead
of  print.

Azaspiracid-59 accumulation and transformation in mussels (Mytilus edulis) after 
feeding with Azadinium poporum (Dinophyceae).

Krock B(1), Mudge EM(2), Müller A(3), Meyer S(4), Tebben J(5), McCarron P(6), 
Abele D(7), Tillmann U(8).

Author information:
(1)Alfred-Wegener-Institut Helmholz-Zentrum für Polar und Meeresforschung, 
Ökologische Chemie. Electronic address: bernd.krock@awi.de.
(2)Biotoxin Metrology, National Research Council of Canada, Halifax, NS B3H 3Z1, 
Canada. Electronic address: Elizabeth.Mudge@nrc-cnrc.gc.ca.
(3)Alfred-Wegener-Institut Helmholz-Zentrum für Polar und Meeresforschung, 
Ökologische Chemie. Electronic address: annegret.mueller@awi.de.
(4)Alfred-Wegener-Institut Helmholz-Zentrum für Polar- und Meeresforschung, 
Benthosökologie. Electronic address: stefanie.meyer@awi.de.
(5)Alfred-Wegener-Institut Helmholz-Zentrum für Polar und Meeresforschung, 
Ökologische Chemie. Electronic address: jan.tebben@awi.de.
(6)Biotoxin Metrology, National Research Council of Canada, Halifax, NS B3H 3Z1, 
Canada. Electronic address: Pearse.McCarron@nrc-cnrc.gc.ca.
(7)Alfred-Wegener-Institut Helmholz-Zentrum für Polar- und Meeresforschung, 
Benthosökologie.
(8)Alfred-Wegener-Institut Helmholz-Zentrum für Polar und Meeresforschung, 
Ökologische Chemie. Electronic address: urban.tillmann@awi.de.

Azaspiracid-59 (AZA-59) was detected in plankton in coastal waters of the 
Pacific Northwest USA. Given that bivalves metabolize and transform accumulated 
phycotoxins, a strain of Azadinium poporum isolated from the coast of Washington 
State that is a known producer of AZA-59 was used in a controlled feeding 
experiment with mussels (Mytilus edulis) to assess AZA-59 accumulation rates and 
transformation into shellfish metabolites. Mussels started feeding immediately 
after the addition of A. poporum. Mussels were generally healthy during the 
entire experimental exposure of 18 days with prevailingly high rates of 
clearance (ca 100 mL per mussel and hour) and ingestion. Mussel were extracted 
after different exposure times and were analyzed by liquid chromatography 
coupled with low- and high-resolution mass spectrometry. In the course of the 
experiment a number of putative AZA-59 metabolites were detected including 
hydroxyl and carboxy analogs that corresponded with previously reported mussel 
metabolites of AZA-1. A significant formation of 3-OH fatty acid acyl esters 
relative to free AZAs was observed through the time course of the study, with 
numerous fatty acid ester variants of AZA-59 confirmed. These results illustrate 
the potential for metabolism of AZA59 in shellfish and provide important 
information for local AZA monitoring and toxicity testing along the Northern 
Pacific US coast.

Copyright © 2024. Published by Elsevier Ltd.

DOI: 10.1016/j.toxicon.2024.108152
PMID: 39490451

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.