Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Diagn Microbiol Infect Dis. 2024 Oct 26;111(1):116578. doi: 
10.1016/j.diagmicrobio.2024.116578. Online ahead of print.

In vitro and silico activity of piperlongumine against 
azole-susceptible/resistant Aspergillus fumigatus and 
terbinafine-susceptible/resistant Trichophyton species.

Haghani I(1), Hashemi SM(2), Abastabar M(1), Yahyazadeh Z(1), Ebrahimi-Barough 
R(1), Hoseinnejad A(3), Teymoori A(4), Azadeh H(5), Rashidi M(6), Aghili SR(1), 
Hedayati MT(1), Shokohi T(1), Otasevic S(7), Sillanpää M(8), Nosratabadi M(9), 
Badali H(10).

Author information:
(1)Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran 
University of Medical Sciences, Sari, Iran; Department of Medical Mycology, 
School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
(2)Department of Medicinal Chemistry and Pharmaceutical Sciences Research 
Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, 
Iran.
(3)Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur 
University of Medical Sciences, Ahvaz, Iran.
(4)Student Research Committee, Faculty of Medicine, Mazandaran University of 
Medical Sciences, Sari, Iran.
(5)Department of Internal Medicine, Rheumatology Division, Orthopedic Research 
Center, Mazandaran University of Medical Sciences, Sari, Iran.
(6)Department Pharmacology, Faculty of Medicine, Mazandaran University of 
Medical Sciences, Sari 4847191628, Iran.
(7)Medical Faculty, University of Niš, 18000 Niš, Serbia.
(8)Functional Materials Group, Gulf University for Science and Technology, 
Mubarak Al-Abdullah, 32093 Kuwait, Kuwait; Centre of Research Impact and 
Outcome, Chitkara University Institute of Engineering and Technology, Chitkara 
University, Rajpura-140401, Punjab, India; Department of Chemical Engineering, 
School of Mining, Metallurgy and Chemical Engineering, University of 
Johannesburg, P. O. Box 17011, Doornfontein 2028, South Africa; Department of 
Civil Engineering, University Centre for Research & Development, Chandigarh 
University, Gharuan, Mohali, Punjab, India; Sustainability Cluster, School of 
Advanced Engineering, UPES, Bidholi, Dehradun, Uttarakhand 248007, India.
(9)Department of Medical Mycology, School of Medicine, Mazandaran University of 
Medical Sciences, Sari, Iran; Department of Laboratory Sciences, Sirjan School 
of Medical Sciences, Sirjan, Iran. Electronic address: 
nosratabadi.mohsen@yahoo.com.
(10)Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran 
University of Medical Sciences, Sari, Iran; Department of Molecular Microbiology 
& Immunology/South Texas Center for Emerging Infectious Diseases, The University 
of Texas at San Antonio, San Antonio, TX, USA.

In recent years, the widespread emergence of drug resistance in yeasts and 
filamentous fungi to existing antifungal armamentariums has become a severe 
threat to global health. There is also concern regarding increased rates of 
azole resistance in Aspergillus fumigatus and Terbinafine resistance in 
Trichophyton species. To overcome this concern of resistance to regular 
therapies, new antifungal drugs with novel and effective mechanisms are 
crucially needed. Herbal remedies may be promising strategies for the treatment 
of resistant infections. We aimed to investigate the in vitro and silico 
activity of piperlongumine against clinical azole susceptible/resistant A. 
fumigatus and terbinafine-susceptible/resistant Trichophyton species. In the 
current study, piperlongumine demonstrated potent antifungal activity, with 
minimum inhibitory concentrations (MICs) ranging from 0.016-4 μg/mL against 
Trichophyton isolates and 0.25-2 μg/mL for A. fumigatus isolates. Additionally, 
molecular docking studies indicated that piperlongumine has a strong binding 
affinity to the active sites of squalene epoxidase and sterol 14-alpha 
demethylase. However, further studies are warranted to correlate these findings 
with clinical outcomes and provide the basis for further investigations to pave 
the way for developing novel antifungal agents.

Copyright © 2024 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.diagmicrobio.2024.116578
PMID: 39500105

Conflict of interest statement: Declaration of competing interest The authors 
declare the following financial interests/personal relationships which may be 
considered as potential competing interests: Dr. Iman Haghani reports financial 
support was provided by Mazandaran University of Medical Sciences. This research 
was financially supported by grant number 17588 from Mazandaran University of 
Medical Sciences. If there are other authors, they declare that they have no 
known competing financial interests or personal relationships that could have 
appeared to influence the work reported in this paper.


2. J Lipid Res. 2024 Oct 25:100684. doi: 10.1016/j.jlr.2024.100684. Online ahead
of  print.

Toxoplasma gondii Sustains Survival by Regulating Cholesterol Biosynthesis and 
Uptake via SREBP2 Activation.

Fan YM(1), Zhang QQ(2), Pan M(2), Hou ZF(2), Fu L(3), Xu X(2), Huang SY(4).

Author information:
(1)Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou 
University, and Jiangsu Co-innovation Center for Prevention and Control of 
Important Animal Infectious Diseases and Zoonosis, and Jiangsu Key Laboratory of 
Zoonosis, Yangzhou, Jiangsu Province 225009, PR China; Joint International 
Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of 
Education of China, Yangzhou University, Yangzhou, PR China.
(2)Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou 
University, and Jiangsu Co-innovation Center for Prevention and Control of 
Important Animal Infectious Diseases and Zoonosis, and Jiangsu Key Laboratory of 
Zoonosis, Yangzhou, Jiangsu Province 225009, PR China.
(3)Chongqing Academy of Animal Sciences, Chongqing, PR China.
(4)Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou 
University, and Jiangsu Co-innovation Center for Prevention and Control of 
Important Animal Infectious Diseases and Zoonosis, and Jiangsu Key Laboratory of 
Zoonosis, Yangzhou, Jiangsu Province 225009, PR China; Joint International 
Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of 
Education of China, Yangzhou University, Yangzhou, PR China; Chongqing Academy 
of Animal Sciences, Chongqing, PR China. Electronic address: 
siyang.huang@hotmail.com.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that cannot 
biosynthesize cholesterol via the mevalonate pathway, it sources this lipid from 
its host. We discovered that T. gondii infection upregulated the expression of 
host cholesterol synthesis related genes HMG-CoA reductase(HMGCR), squalene 
epoxidase (SQLE) and dehydrocholesterol reductase-7 (DHCR7), and increased the 
uptake pathway gene low-density lipoprotein receptor (LDLR). We found a protein, 
sterol regulatory element binding protein 2 (SREBP2), which is the key protein 
regulating the host cholesterol synthesis and uptake during T. gondii infection. 
T. gondii induced a dose-dependent nuclear translocation of SREBP2. Knockdown 
SREBP2 reduced T. gondii-induced cholesterol biosynthesis and uptake. 
Consequently, the parasite's ability to acquire cholesterol was significantly 
diminished, impairing its invasion, replication, and bradyzoites development. 
Interfering cholesterol metabolism using AY9944 effectively inhibited T. gondii 
replication. In summary, SREBP2 played an important role in T. gondii infection 
in vitro, serving as a potential target for regulating T. gondii-induced 
cholesterol metabolism, offering insights into the prevention and treatment of 
toxoplasmosis.

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

DOI: 10.1016/j.jlr.2024.100684
PMID: 39490926

Conflict of interest statement: Conflict of interest The authors declare that 
they have no conflicts of interest with the contents of this article.


3. Int J Pharm. 2024 Oct 26:124870. doi: 10.1016/j.ijpharm.2024.124870. Online 
ahead of print.

Raman imaging for monitoring deuterated squalene-gemcitabine nanomedicines in 
single living breast cancer cells.

Al Assaad A(1), Alaouta C(1), Desmaele D(2), Buache E(1), Fossier E(1), Van 
Gulick L(1), Slimano F(1), Dukic S(1), Mura S(2), Morjani H(1), Beljebbar A(3).

Author information:
(1)Université de Reims Champagne Ardenne, BioSpecT- UR 7506, UFR de Pharmacie, 
51096, Reims, France.
(2)Université Paris-Saclay, UMR CNRS8612, Institut Galien Paris-Saclay, 17, 
Avenue des Sciences 91400, Orsay, France.
(3)Université de Reims Champagne Ardenne, BioSpecT- UR 7506, UFR de Pharmacie, 
51096, Reims, France. Electronic address: abdelilah.beljebbar@univ-reims.fr.

We have investigated the impact of gemcitabine (Gem) and deuterated 
gemcitabine-squalene (GemSQ-d6) nanoparticles (NPs) on MCF7 and MDA-MB-231 
breast cancer cell lines by Raman spectroscopy. Quantification of LDL expression 
levels in both cell lines revealed a four-fold increase in MDA-MB-231 cells 
compared to MCF7 cells. In in vitro antitumor assessments, Gem displayed 13.5 
times more effectiveness than GemSQ NPs against MCF7 cells, whereas GemSQ NPs 
induced a 14-fold increase in cytotoxicity compared to Gem for MDA-MB-231 cells. 
Oil Red O staining revealed that the treatment with GemSQ-d6 NPs induced a 
higher accumulation of lipid droplets at the periphery of the nucleus in 
MDA-MB-231 cells compared to MCF7 cells. Raman spectroscopy was employed to 
assess the impact of these drugs (50 µM, 24 h) on these breast cancer cell 
lines. By using the silent region (2000-2400 cm-1), we demonstrated that the 
accumulation of the GemSQ-d6 bioconjugate was higher in the cytoplasm of 
MDA-MB-231 cells than in MCF7 cells. This difference in drug accumulation is 
likely correlated with their expression levels of LDL receptors (LDLR) However, 
no information was obtained on Gem in this spectral region. We identified Raman 
features of squalene (SQ) in 700-1800 cm-1 fingerprint region that allowed us to 
observe almost the same distribution of GemSQ as that observed in the silent 
region for both cell lines treated with GemSQ-d6 or SQ-d6. Subsequently, the 
effects of Gem and GemSQ-d6 on cellular components such as proteins, nucleic 
acids, and cytochrome C were monitored within the fingerprint spectral region. 
Our results revealed distinct features in the subcellular accumulation of these 
biomolecules in response to Gem and GemSQ treatments.

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

DOI: 10.1016/j.ijpharm.2024.124870
PMID: 39490555

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.


4. Biomater Adv. 2024 Oct 23;166:214076. doi: 10.1016/j.bioadv.2024.214076.
Online  ahead of print.

The aluminum nanoparticle-encircled SQ-in-water emulsions (ANSWE) as a vaccine 
adjuvant-delivery system (VADS) for developing robust mucosal subunit vaccines.

Gao Y(1), Wang N(2), Qi Y(1), Wang X(1), Zhang K(1), Zhang Y(1), Cao Y(1), Zang 
T(1), Wang T(3).

Author information:
(1)School of Pharmacy, Anhui Medical University, 81 Plum Hill Road, Hefei, Anhui 
Province 230032, China.
(2)School of Food and Bioengineering, Hefei University of Technology, 420 Jade 
Road, Hefei, Anhui Province 230601, China.
(3)School of Pharmacy, Anhui Medical University, 81 Plum Hill Road, Hefei, Anhui 
Province 230032, China. Electronic address: twangcn@hotmail.com.

The aluminum nanoparticle-encircled squalene (SQ)-in-water emulsions (ANSWE) 
were engineered as a VADS (vaccine adjuvant-delivery system) using a simple 
procedure for carrying antigens (Ag) to develop subunit vaccines. In vitro, due 
to possessing the synergistic adjuvanticity of both AN and SQ, ANSWE were 
efficiently taken up by APC (antigen-presenting cells) and triggered them to 
mature and make extra ROS (reactive oxygen species) and multiple cytokines, such 
as IL-12, IL-1β and IFN-β, which favor balanced Th1/Th2 immunoresponses. Within 
APC, ANSWE managed lysosome escape and consequently enhanced proteasome 
activities to facilitate Ag cross-presentation. Mice given twice ovalbumin-ANSWE 
via intrapulmonary vaccination (IPV) produced high levels of anti-Ag antibodies 
as well as cytotoxic T lymphocytes, which efficiently erased cells bearing 
cognate Ag. Thus, ANSWE as a potent VADS may be feasible for developing mucosal 
subunit vaccines that can elicit comprehensive immunity against infectious 
diseases, including especially the respiratory infections, and even aggressive 
cancers.

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

DOI: 10.1016/j.bioadv.2024.214076
PMID: 39490192

Conflict of interest statement: Declaration of competing interest All the 
authors declared no conflict of interests.


5. ACS Sustain Chem Eng. 2024 Oct 17;12(43):16052-16063. doi: 
10.1021/acssuschemeng.4c05897. eCollection 2024 Oct 28.

Screening and Characterization of 1,8-Cineole-Based Solvents as an Alternative 
to Hexane for Obtaining Nonpolar Compounds from Plant-Based Milk Coproducts.

Strieder MM(1)(2), Bragagnolo FS(2), Mendiola JA(1), Rostagno MA(2), Ibáñez 
E(1).

Author information:
(1)Foodomics Laboratory, Instituto de Investigación en Ciencias de la 
Alimentación (CIAL, CSIC-UAM), Madrid 28049, Spain.
(2)Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied 
Sciences (FCA), Universidade Estadual de Campinas, Campinas, São Paulo 
13484-350, Brazil.

The design of new hydrophobic solvents is essential for replacing the toxic 
hexane for extracting nonpolar compounds such as fatty acids. On the other hand, 
the full use of plant matrices seeking to obtain new food and pharmaceutical 
products from their coproducts has also been the focus of sustainable processes. 
This study proposed new solvents for replacing hexane to extract fatty acids and 
hydrophobic bioactive compounds from coproducts obtained from almond- and 
peanut-based milk processing. The COSMO-RS method was used to select 
terpene-based mixtures to substitute hexane. Experimentally, four liquid 
solvents were formed from 1:2 tetradecanol/1,8-cineole (TE/EU), 1:2 
camphor/1,8-cineole (CA/EU), 1:1 oleic acid/1,8-cineole (OL/EU), and 1:1 
menthol/1,8-cineole (ME/EU). DSC analyses indicated the reduction of the CA/EU, 
OL/EU, and ME/EU melting points concerning their components. However, the 
melting point values predicted by the COSMO for obtaining eutectic mixtures 
differed. CA/EU was the only mixture with a melting point lower than the 
COSMO-RS-predicted one. In contrast, the FTIR spectra did not provide a clear 
visualization of the hydrogen bond formation between camphor and 1,8-cineole. 
This could be due to the formation of weak hydrogen bonds, a phenomenon observed 
in other studies. Nevertheless, these solvents have the advantage of low 
viscosity, a promising feature that likely facilitated mass transfer in the 
extraction of hydrophobic compounds from almond and peanut coproducts. ME/EU 
provided the same global extraction yield as hexane and higher phytosterol 
extraction from almond coproducts. On the other hand, CA/EU provided the same 
global yield and squalene content as hexane from peanut coproducts. The extracts 
can be directly used in food and pharmaceutical applications since the solvents 
are usually part of the formulations. However, DSC and TGA-DTA analyses 
indicated possible ways to separate the solvents.

© 2024 The Authors. Published by American Chemical Society.

DOI: 10.1021/acssuschemeng.4c05897
PMCID: PMC11524417
PMID: 39483209

Conflict of interest statement: The authors declare no competing financial 
interest.