Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. BMC Microbiol. 2024 Nov 6;24(1):451. doi: 10.1186/s12866-024-03585-x.

Exploring the lipids, carotenoids, and vitamins content of Rhodotorula glutinis 
with selenium supplementation under lipid accumulating and growth proliferation 
conditions.

Elfeky N(1), Rizk A(2), Gharieb MM(2).

Author information:
(1)Botany and Microbiology Department, Faculty of Science, Menoufia University, 
Menoufia, Egypt. n0ra.mohamed1987@yahoo.com.
(2)Botany and Microbiology Department, Faculty of Science, Menoufia University, 
Menoufia, Egypt.

BACKGROUND: Rhodotorula glutinis, a specific type of yeast, has been recognised 
as a superior resource for generating selenium-enriched biomass that possesses 
exceptional nutritional and functional attributes. The purpose of this 
investigation was to assess the effect of sodium selenite at different 
concentrations on lipid and carotenoid synthesis, as well as the growth of R. 
glutinis.
METHODS: The lipid's fatty acid composition was determined using gas 
chromatography (GC). The vitamins were detected by high-performance liquid 
chromatography (HPLC). Transmission electron microscopy was used to detect the 
structural modification of yeast cells caused by the addition of sodium selenite 
to the growth medium, as well as the accumulation of elemental selenium in the 
yeast cells.
RESULTS: The yeast cells demonstrated the ability to endure high concentrations 
of sodium selenite under lipid accumulation (LAM) and growth-promoting (YPD) 
conditions. 25.0 mM and 30.0 mM, respectively, were published as the IC50 values 
for the LAM and YPD conditions. In both growth media, 1 mM sodium selenite 
boosted lipid synthesis. Lipid accumulation increased 26% in LAM to 11.4 g/l and 
18% in YPD to 4.3 g/l. Adding 1 mM and 3 mM sodium selenite to YPD medium 
increased total and cellular carotenoids by 22.8% (646.7 µg/L and 32.12 µg/g) 
and 48.7% (783.3 µg/L and 36.43 µg/g), respectively. Palmitic acid was 
identified as the most abundant fatty acid in all treatments, followed by oleic 
acid and linoleic acid. The concentrations of water soluble vitamins (WSV) and 
fat soluble vitamins (FSV) were generally significantly increased after 
supplementation with 1.0 mM sodium selenite. TEM examination revealed a 
significant reduction in lipid bodies accumulation in the yeast cells when 
sodium selenite was added to lipid-promoting environments. This decline is 
accompanied by an augmentation in the formation of peroxisomes, indicating that 
selenium has a direct impact on the degradation of fatty acids. In addition, 
autophagy appears to be the primary mechanism by which selenium ions are 
detoxified. Additionally, intracellular organelles disintegrate, cytoplasmic 
vacuolization occurs, and the cell wall and plasma membrane rupture, resulting 
in the discharge of cytoplasmic contents, when a high concentration of sodium 
selenite (20.0 mM) is added. Also, the presence of numerous electron-dense 
granules suggests an intracellular selenium-detoxification pathway.
CONCLUSION: This study proposes the use of YPD with 1 mM sodium selenite to 
cultivate selenium-enriched biomass from R. glutinis. This approach leads to 
heightened lipid levels with higher accumulation of oleic, linoleic and 
linolenic acids, carotenoids, and vitamins. Hence, this biomass has the 
potential to be a valuable additive for animal, fish, and poultry feed. 
Furthermore, explain certain potential factors that indicate the impact of 
selenium in reducing the accumulation of lipid droplets in R. glutinis during 
lipogenesis, as detected through TEM examination.

© 2024. The Author(s).

DOI: 10.1186/s12866-024-03585-x
PMID: 39506648 [Indexed for MEDLINE]


2. Comb Chem High Throughput Screen. 2024 Nov 6. doi: 
10.2174/0113862073330016240911094247. Online ahead of print.

Preparation of DOX-TPP/HA-ss-OA Nanoparticles, Investigation of Drug Release 
Behavior In Vitro, and Evaluation of Anti-proliferative Activity In Vitro.

Fei X(1), Hu Q(1).

Author information:
(1)School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510000, 
China.

OBJECTIVE: This study aimed to develop and characterize DOX-TPP/HA-ss-OA 
nanoparticles, utilizing the mitochondria-targeting prodrug 
doxorubicin-triphenylphosphine (DOXTPP) and a reduction-sensitive amphiphilic 
polymer, hyaluronic acid-disulfide-oleic acid (HAss- OA). The research focused 
on evaluating the drug release behavior of these nanoparticles under varying 
glutathione (GSH) concentrations and their anti-tumor activity in vitro.
METHODS: DOX-TPP/HA-ss-OA nanoparticles were prepared using probe ultrasound 
technology. The study examined the impact of different organic solvents on drug 
loading capacity and encapsulation efficiency to determine the optimal 
conditions. A single-factor experimental design was used to optimize the 
formulation process. Key parameters, including particle size and zeta potential, 
were measured to assess nanoparticle stability and performance. The dynamic 
dialysis method was employed to evaluate the reduction-sensitive drug release 
characteristics in media with different GSH concentrations. The MTT assay was 
used to analyze the growth-inhibitory effects of the nanoparticles on human 
breast cancer cells (MCF-7) and drug-resistant cells (MCF-7/ADR).
RESULTS: The optimized preparation process for DOX-TPP/HA-ss-OA nanoparticles 
included a drug dosage of 2.0 mg, an oil-to-water volume ratio of 1:5, 
ultrasonic power of 500 W, and ultrasonic time of 15 minutes. The nanoparticles 
had an average particle size of 203.72 ± 2.30 nm and a zeta potential of 25.82 ± 
0.58 mV, indicating favorable stability and effective drug delivery properties. 
The nanoparticles exhibited a slow, sustained release of DOX-TPP in pH 7.4 
phosphate buffer solution (PBS) and accelerated release in high GSH 
concentrations, demonstrating reduction-responsive drug release. In vitro 
studies showed that DOX-TPP/HA-ss-OA nanoparticles significantly inhibited the 
proliferation of MCF-7 and MCF-7/ADR cells in a dosedependent manner, with 
enhanced efficacy compared to free DOX and other formulations.
CONCLUSION: DOX-TPP/HA-ss-OA nanoparticles demonstrate excellent reduction 
sensitivity, effective tumor cell growth inhibition in vitro, and the ability to 
overcome drug resistance. Including particle size and zeta potential 
measurements supports their suitability as drug carriers, highlighting their 
potential for targeted cancer therapy and further development.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0113862073330016240911094247
PMID: 39506424


3. J Lipid Res. 2024 Nov 4:100692. doi: 10.1016/j.jlr.2024.100692. Online ahead
of  print.

Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and 
abolished by PPARα activation in liver cells.

Moliterni C(1), Vari F(2), Schifano E(1), Tacconi S(3), Stanca E(4), Friuli 
M(5), Longo S(4), Conte M(6), Salvioli S(7), Gnocchi D(8), Mazzocca A(8), 
Uccelletti D(1), Vergara D(4), Dini L(9), Giudetti AM(10).

Author information:
(1)Department of Biology and Biotechnology "C. Darwin", Sapienza University of 
Rome, Rome, Italy.
(2)Department of Biological and Environmental Sciences and Technologies, 
University of Salento, 73100 Lecce, Italy; Department of Physiology and 
Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 
00185, Rome, Italy.
(3)Department of Biology and Biotechnology "C. Darwin", Sapienza University of 
Rome, Rome, Italy; CarMeN Laboratory (UMR INSERM 1060/INRA 1397), HCL, Lyon 1 
University, Pierre-Bénite, France.
(4)Department of Biological and Environmental Sciences and Technologies, 
University of Salento, 73100 Lecce, Italy.
(5)Department of Physiology and Pharmacology "V. Erspamer", Sapienza University 
of Rome, P.le Aldo Moro 5, 00185, Rome, Italy.
(6)Department of Medical and Surgical Sciences, University of Bologna, 40138 
Bologna, Italy.
(7)Department of Medical and Surgical Sciences, University of Bologna, 40138 
Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 
Bologna, Italy.
(8)Interdisciplinary Department of Medicine, University of Bari School of 
Medicine, 70124 Bari, Italy.
(9)Department of Biology and Biotechnology "C. Darwin", Sapienza University of 
Rome, Rome, Italy. Electronic address: anna.giudetti@unisalento.it.
(10)Department of Biological and Environmental Sciences and Technologies, 
University of Salento, 73100 Lecce, Italy. Electronic address: 
anna.giudetti@unisalento.it.

Lipotoxicity refers to the harmful effects of excess fatty acids on metabolic 
health, and it can vary depending on the type of fatty acids involved. Saturated 
and unsaturated fatty acids exhibit distinct effects, though the precise 
mechanisms behind these differences remain unclear. Here, we investigated the 
lipotoxicity of palmitic acid (PA), a saturated fatty acid, compared with oleic 
acid (OA), a monounsaturated fatty acid, in the hepatic cell line HuH7. Our 
results demonstrated that PA, unlike OA, induces lipotoxicity, endoplasmic 
reticulum (ER) stress, and autophagy inhibition. Compared with OA, PA treatment 
leads to less lipid droplet (LD) accumulation and a significant reduction in the 
mRNA and protein level of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme 
of triacylglycerol synthesis. Using modulators of ER stress and autophagy, we 
established that DGAT1 downregulation by PA is closely linked to these cellular 
pathways. Notably, the ER stress inhibitor 4-phenylbutyrate can suppress 
PA-induced DGAT1 downregulation. Furthermore, knockdown of DGAT1 by siRNA or 
with A922500, a specific DGAT1 inhibitor, resulted in cell death, even with OA. 
Both PA and OA increased the oxygen consumption rate; however, the increase 
associated with PA was only partially coupled to ATP synthesis. Importantly, 
treatment with GW7647 a specific PPARα agonist mitigated the lipotoxic effects 
of PA, restoring PA-induced ER stress, autophagy block, and DGAT1 suppression. 
In conclusion, our study highlights the crucial role of DGAT1 in PA-induced 
lipotoxicity, broadening the knowledge of the mechanisms underlying hepatic 
lipotoxicity and providing the basis for potential therapeutic interventions.

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jlr.2024.100692
PMID: 39505261


4. J Immunother Cancer. 2024 Nov 5;12(11):e010422. doi: 10.1136/jitc-2024-010422.

WWOX tuning of oleic acid signaling orchestrates immunosuppressive macrophage 
polarization and sensitizes hepatocellular carcinoma to immunotherapy.

Liu S(#)(1), Yang S(#)(2), Xu M(#)(1), Zhou Q(1), Weng J(1), Hu Z(2), Xu M(1), 
Xu W(1), Yi Y(1), Shi Y(3), Dong Q(2), Hung MC(4), Ren N(5), Zhou C(5).

Author information:
(1)Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and 
Cancer Invasion, Ministry of Education, Shanghai, China.
(2)Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan 
University, Shanghai, China.
(3)Biomedical Research Centre, Zhongshan Hospital, Fudan University, Shanghai, 
China.
(4)Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology 
and Center for Molecular Medicine, China Medical University, Taichung, Taiwan 
zhouchenhao@fudan.edu.cn mhung@cmu.edu.tw ren.ning@zs-hospital.sh.cn.
(5)Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and 
Cancer Invasion, Ministry of Education, Shanghai, China zhouchenhao@fudan.edu.cn 
mhung@cmu.edu.tw ren.ning@zs-hospital.sh.cn.
(#)Contributed equally

BACKGROUND: Immune checkpoint inhibitors (ICIs) are therapeutically effective 
for hepatocellular carcinoma (HCC) but are individually selective. This study 
examined the role of specific common fragile sites (CFSs) related gene in HCC 
immunotherapy.
METHODS: We analyzed HCC tissues using next-generation sequencing and flow 
cytometry via time-of-flight technology. A humanized orthotopic HCC mouse model, 
an in vitro co-culture system, untargeted metabolomics and a DNA pulldown assay 
were used to examine the function and mechanism of WWOX in the tumor immune 
response.
RESULTS: WWOX was the most upregulated CFS-related gene in HCC patients 
responsive to ICIs. WWOX deficiency renders HCC resistant to PD-1 treatment in 
humanized orthotopic HCC mouse model. Macrophage infiltration is increased and 
CD8 T-cell subset infiltration is decreased in WWOX-deficient HCC patients. 
HCC-derived oleic acid (OA) promotes macrophage conversion to an 
immunosuppressive phenotype. Mechanistically, WWOX deficiency promoted OA 
synthesis primarily via competitive binding of NME2 with KAT1, which promoted 
acetylation of NME2 at site 31 and inhibited NME2 binding to the SCD5 promoter 
region. Pharmacological blockade of SCD5 enhanced the antitumor effects of 
anti-PD-1 therapy.
CONCLUSIONS: WWOX is a key factor for immune escape in HCC patients, which 
suggests its use as a biomarker for stratified treatment with ICIs in clinical 
HCC patients.

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No 
commercial re-use. See rights and permissions. Published by BMJ.

DOI: 10.1136/jitc-2024-010422
PMID: 39500530 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: None declared.


5. Biochim Biophys Acta Biomembr. 2024 Nov 3:184395. doi: 
10.1016/j.bbamem.2024.184395. Online ahead of print.

Growth of Staphylococcus aureus in the presence of oleic acid shifts the 
glycolipid fatty acid profile and increases resistance to antimicrobial 
peptides.

Raskovic D(1), Alvarado G(2), Hines KM(3), Xu L(4), Gatto C(5), Wilkinson BJ(5), 
Pokorny A(6).

Author information:
(1)Department of Chemistry and Biochemistry, University of North Carolina 
Wilmington, Wilmington, NC, United States of America.
(2)Department of Molecular Biosciences, Northwestern University, Evanston, IL, 
United States of America; School of Biological Sciences, Illinois State 
University, Normal, IL, United States of America.
(3)Department of Chemistry, University of Georgia, Athens, GA, United States of 
America.
(4)Department of Medicinal Chemistry, University of Washington, Seattle, WA, 
United States of America.
(5)School of Biological Sciences, Illinois State University, Normal, IL, United 
States of America.
(6)Department of Chemistry and Biochemistry, University of North Carolina 
Wilmington, Wilmington, NC, United States of America. Electronic address: 
almeidaa@uncw.edu.

Staphylococcus aureus readily adapts to various environments and quickly 
develops antibiotic resistance, which has led to an increase in 
multidrug-resistant infections. Hence, S. aureus presents a significant global 
health issue and its adaptations to the host environment are crucial for 
understanding pathogenesis and antibiotic susceptibility. When S. aureus is 
grown conventionally, its membrane lipids contain a mix of branched-chain and 
straight-chain saturated fatty acids. However, when unsaturated fatty acids are 
present in the growth medium, they become a major part of the total fatty acid 
composition. This study explores the biophysical effects of incorporating 
straight-chain unsaturated fatty acids into S. aureus membrane lipids. Membrane 
preparations from cultures supplemented with oleic acid showed more complex 
differential scanning calorimetry scans than those grown in tryptic soy broth 
alone. When grown in the presence of oleic acid, the cultures exhibited a 
transition significantly above the growth temperature, attributed to the 
presence of glycolipids with long-chain fatty acids causing acyl chain packing 
frustration within the bilayer. Functional aspects of the membrane were assessed 
by studying the kinetics of dye release from unilamellar vesicles induced by the 
antimicrobial peptide mastoparan X. Dye release was slower from liposomes 
prepared from cells grown in oleic acid-supplemented cultures, suggesting that 
changes in membrane lipid composition and biophysics protect the cell membrane 
against peptide-induced lysis. These findings underscore the intricate 
relationship between the growth environment, membrane lipid composition, and the 
physical properties of the bacterial membrane, which should be considered when 
developing new strategies against S. aureus infections.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.bbamem.2024.184395
PMID: 39500386

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.