Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Genes Cancer. 2024 Aug 9;15:41-59. doi: 10.18632/genesandcancer.237.
eCollection  2024.

Dialyl-sulfide with trans-chalcone prevent breast cancer prohibiting SULT1E1 
malregulations and oxidant-stress induced HIF1a-MMPs induction.

Nazmeen A(1), Maiti S(1), Maiti S(2)(3).

Author information:
(1)Department of Biochemistry, Cell and Molecular Therapeutics Lab, Oriental 
Institute of Science and Technology, Midnapore 721101, India.
(2)Haldia Institute of Health Sciences, ICARE, Haldia, East Midnapore, India.
(3)AgriCure Biotech Research Society, Midnapore, WB, India.

BACKGROUND: In some breast cancers, altered estrogen-sulfotransferase (SULT1E1) 
and its inactivation by oxidative-stress modifies E2 levels. Parallelly, 
hypoxia-inducible tissue-damaging factors (HIF1α) are induced. The 
proteins/genes expressions of these factors were verified in human-breast-cancer 
tissues. SULT1E1 inducing-drugs combinations were tested for their possible 
protective effects.
METHODS: Matrix-metalloproteases (MMP2/9) activity and SULT1E1-HIF1α 
protein/gene expression (Western-blot/RTPCR) were assessed in breast-cancers 
versus adjacent-tissues. Oxidant-stress neutralizer, chalcone 
(trans-1,3-diaryl-2-propen-1-ones) and SULT1E1-inducer pure dialyl-sulfide 
(garlic; Allium sativum) were tested to prevent cancer causing factors in rat, 
in-vitro and in-vivo. The antioxidant-enzymes SOD1/catalase/GPx/LDH and 
matrix-degenerating MMP2/9 activities were assessed (gel-zymogram). 
Histoarchitecture (HE-staining) and tissue SULT1E1-localization 
(immuno-histochemistry) were screened. Extensive statistical-analysis were 
performed.
RESULTS: Human cancer-tissue expresses higher SULT1E1, HIF1α protein/mRNA and 
lower LDH activity. Increase of MMP2/9 activities commenced tissue damage. 
However, chalcone and DAS significantly induced SULT1E1 gene/protein, suppressed 
HIF1α expression, MMP2/9 activities in rat tissues. Correlation and group 
statistics of t-test suggest significant link of oxidative-stress (MDA) with 
SULT1E1 (p = 0.006), HIF1α (p = 0.006) protein-expression. The 
non-protein-thiols showed negative correlation (p = 0.001) with HIF1α. These 
proteins and SULT1E1-mRNA expressions were significantly higher in tumor (p < 
0.05). Correlation data suggest, SULT1E1 is correlated with non-protein-thiols.
CONCLUSIONS: Breast cancers associate with SULT1E1, HIF1α and MMPs 
deregulations. For the first time, we are revealing that advanced cancer tissue 
with elevated SULT1E1-protein may reactivate in a reducing-state initiated by 
chalcone, but remain dormant in an oxidative environment. Furthermore, increased 
SULT1E1 protein synthesis is caused by DAS-induced mRNA expression. The combined 
effects of the drugs might decrease MMPs and HIF1α expressions. Further studies 
are necessary.

DOI: 10.18632/genesandcancer.237
PMCID: PMC11315411
PMID: 39132498

Conflict of interest statement: CONFLICTS OF INTEREST Authors have no conflicts 
of interest to declare.


2. Antioxid Redox Signal. 2023 Nov;39(13-15):983-999. doi: 10.1089/ars.2023.0405.
 Epub 2023 Sep 19.

Persulfide Biosynthesis Conserved Evolutionarily in All Organisms.

Ogata S(1), Matsunaga T(1), Jung M(1), Barayeu U(1), Morita M(1), Akaike T(1).

Author information:
(1)Department of Environmental Medicine and Molecular Toxicology, Tohoku 
University Graduate School of Medicine, Sendai, Japan.

Significance: Persulfides/polysulfides are sulfur-catenated molecular species 
(i.e., R-Sn-R', n > 2; R-Sn-H, n > 1, with R = cysteine, glutathione, and 
proteins), such as cysteine persulfide (CysSSH). These species are abundantly 
formed as endogenous metabolites in mammalian and human cells and tissues. 
However, the persulfide synthesis mechanism has yet to be thoroughly discussed. 
Recent Advances: We used β-(4-hydroxyphenyl)ethyl iodoacetamide and mass 
spectrometry to develop sulfur metabolomics, a highly precise, quantitative 
analytical method for sulfur metabolites. Critical Issues: With this method, we 
detected appreciable amounts of different persulfide species in biological 
specimens from various organisms, from the domains Bacteria, Archaea, and 
Eukarya. By using our rigorously quantitative approach, we identified 
cysteinyl-tRNA synthetase (CARS) as a novel persulfide synthase, and we found 
that the CysSSH synthase activity of CARS is highly conserved from the domains 
Bacteria to Eukarya. Because persulfide synthesis is found not only with CARS 
but also with other sulfotransferase enzymes in many organisms, 
persulfides/polysulfides are expected to contribute as fundamental elements to 
substantially diverse biological phenomena. In fact, persulfide generation in 
higher organisms-that is, plants and animals-demonstrated various physiological 
functions that are mediated by redox signaling, such as regulation of energy 
metabolism, infection, inflammation, and cell death, including ferroptosis. 
Future Directions: Investigating CARS-dependent persulfide production may 
clarify various pathways of redox signaling in physiological and 
pathophysiological conditions and may thereby promote the development of 
preventive and therapeutic measures for oxidative stress as well as different 
inflammatory, metabolic, and neurodegenerative diseases. Antioxid. Redox Signal. 
39, 983-999.

DOI: 10.1089/ars.2023.0405
PMCID: PMC10655014
PMID: 37565274 [Indexed for MEDLINE]

Conflict of interest statement: No competing financial interests exist.


3. Res Microbiol. 2023 Nov-Dec;174(8):104108. doi: 10.1016/j.resmic.2023.104108. 
Epub 2023 Jul 27.

Phosphate starvation is accompanied by disturbance of intracellular cysteine 
homeostasis in Escherichia coli.

Smirnova GV(1), Tyulenev AV(2), Bezmaternykh KV(3), Muzyka NG(4), Ushakov VY(5), 
Oktyabrsky ON(6).

Author information:
(1)Institute of Ecology and Genetics of Microorganisms, Perm Federal Research 
Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. 
Electronic address: smirnova@iegm.ru.
(2)Institute of Ecology and Genetics of Microorganisms, Perm Federal Research 
Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. 
Electronic address: leksey333@yandex.ru.
(3)Institute of Ecology and Genetics of Microorganisms, Perm Federal Research 
Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. 
Electronic address: hydrargyrum@iegm.ru.
(4)Institute of Ecology and Genetics of Microorganisms, Perm Federal Research 
Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. 
Electronic address: mu2ykana@mail.ru.
(5)Institute of Ecology and Genetics of Microorganisms, Perm Federal Research 
Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. 
Electronic address: ushakovvad@yandex.ru.
(6)Institute of Ecology and Genetics of Microorganisms, Perm Federal Research 
Center, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. 
Electronic address: oktyabr@iegm.ru.

Metabolic rearrangements that occur during depletion of essential nutrients can 
lead to accumulation of potentially dangerous metabolites. Here we showed that 
depletion of phosphate (Pi), accompanied by a sharp inhibition of growth and 
respiration, caused a transient excess of intracellular cysteine due to a 
decrease in the rate of protein synthesis. High cysteine level can be dangerous 
due to its ability to produce ROS and reduce Fe3+ to Fenton-reactive Fe2+. To 
prevent these negative effects, excess cysteine was mainly incorporated into 
glutathione (GSH), the intracellular level of which increased by 3 times, and 
was also exported to the medium and partially degraded to form H2S with 
participation of 3-mercaptopyruvate sulfotransferase (3MST). The addition of Pi 
to starving cells led to a sharp recovery of respiration and growth, GSH efflux 
into the medium and K+ influx into the cells. A pronounced coupling of Pi, GSH, 
and K+ fluxes was shown upon Pi depletion and addition, which may be necessary 
to maintain the ionic balance in the cytoplasm. We suggest that processes aimed 
at restoring cysteine homeostasis may be an integral part of the universal 
response to stress under different types of stress and for different types of 
bacteria.

Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights 
reserved.

DOI: 10.1016/j.resmic.2023.104108
PMID: 37516155 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest All authors 
declare that they have no conflict of interest.


4. Cell Biochem Funct. 2023 Jun;41(4):461-477. doi: 10.1002/cbf.3796. Epub 2023
May  4.

Significant impact of redox regulation of estrogen-metabolizing proteins on 
cellular stress responses.

Maiti S(1), Nazmeen A(1), Banerjee A(1).

Author information:
(1)Department of Biochemistry, Cell & Molecular Therapeutics Lab, Oriental 
Institute of Science & Technology, Midnapore, India.

The ultimate driving force, stress, promotes adaptability/evolution in 
proliferating organisms, transforming tumorigenic growth. Estradiol (E2) 
regulates both phenomena. In this study, bioinformatics-tools, 
site-directed-mutagenesis (human estrogen-sulfotransferase/hSULT1E1), HepG2 
cells tested with N-acetyl-cysteine (NAC/thiol-inducer) or 
buthionine-sulfoxamine (BSO/thiol-depletory) were evaluated for hSULT1E1 
(estradiol-sulphating/inactivating) functions. Reciprocal redox regulation of 
steroid sulfatase (STS, E2-desulfating/activating) results in the 
Cys-formylglycine transition by the formylglycine-forming enzyme (FGE). The 
enzyme sequences and structures were examined across the phylogeny. Motif/domain 
and the catalytic conserve sequences and protein-surface-topography (CASTp) were 
investigated. The E2 binding to SULT1E1 suggests that the 
conserved-catalytic-domain in this enzyme has critical Cysteine 83 at position. 
This is strongly supported by site-directed mutagenesis/HepG2-cell research. 
Molecular-docking and superimposition studies of E2 with the SULT1E1 of 
representative species and to STS reinforce this hypothesis. SULT1E1-STS are 
reciprocally activated in response to the cellular-redox-environment by the 
critical Cys of these two enzymes. The importance of E2 in organism/species 
proliferation and tissue tumorigenesis is highlighted.

© 2023 John Wiley & Sons Ltd.

DOI: 10.1002/cbf.3796
PMID: 37139830 [Indexed for MEDLINE]


5. Chem Res Toxicol. 2022 Jul 18;35(7):1257-1266. doi: 
10.1021/acs.chemrestox.2c00054. Epub 2022 Jun 28.

Metabolic Activation of Gemfibrozil Mediated by Cytochrome P450 Enzymes and 
Sulfotransferases.

Zhao M(1), Shi J(1), Li W(1), Guan C(1), Sun C(1), Peng Y(1), Zheng J(1)(2)(3).

Author information:
(1)Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 
Liaoning 110016, P. R. China.
(2)State Key Laboratory of Functions and Applications of Medicinal Plants, Key 
Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, 
Guiyang, Guizhou 550025, P. R. China.
(3)Key Laboratory of Environmental Pollution, Monitoring and Disease Control, 
Ministry of Education, Guizhou Medical University, Guiyang, Guizhou 550025, P. 
R. China.

Gemfibrozil (GEM), a lipid regulator, is a fibric acid derivative widely used in 
the treatment of hyperlipidemia. It has been reported that GEM can induce acute 
liver injury in the course of therapy in clinical practice, so it is necessary 
to elucidate the mechanisms of toxic action. The present study focused on 
metabolic activation of GEM, possibly participating in GEM-mediated liver 
injury. A benzylic alcohol metabolite (M1), along with a phenol metabolite (M2), 
was detected in microsomal incubations, rat primary hepatocyte culturing, and 
rats given GEM. A GSH conjugate (M3) was detected in cultured rat hepatocytes 
after exposure to GEM. Formation of M1 was found to be NADPH dependent, and 
generation of M3 required M1 and 3'-phosphoadenosine-5'-phosphosulfate. It is 
most likely that GEM was biotransformed to M1, which was further metabolized to 
a sulfate. The resulting sulfate was reactive to bio-thiols. Cytochrome P450 and 
sulfotransferases participated in the phase I and phase II reactions, 
respectively. M1 and M3 were chemically synthesized, and their structures were 
characterized by mass spectrometry and NMR. The present study has particular 
value for elucidating the mechanism of liver injury caused by GEM.

DOI: 10.1021/acs.chemrestox.2c00054
PMID: 35763595 [Indexed for MEDLINE]