Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Med Chem. 2024 Mar 14;67(5):3626-3642. doi: 10.1021/acs.jmedchem.3c02107.
Epub  2024 Feb 21.

Discovery of 5-Hydroxy-1,4-naphthoquinone (Juglone) Derivatives as Dual 
Effective Agents Targeting Platelet-Cancer Interplay through Protein Disulfide 
Isomerase Inhibition.

Juang YP(1), Tsai JY(2), Gu WL(1), Hsu HC(2), Lin CL(1), Wu CC(2), Liang 
PH(1)(3).

Author information:
(1)School of Pharmacy, College of Medicine, National Taiwan University, Taipei 
100, Taiwan.
(2)Graduate Institute of Natural Product, Kaohsiung Medical University, 
Kaohsiung 807, Taiwan.
(3)The Genomics Research Center, Academia Sinica, Taipei 128, Taiwan.

In this study, a series of 2- and/or 3-substituted juglone derivatives were 
designed and synthesized. Among them, 9, 18, 22, 30, and 31 showed stronger 
inhibition activity against cell surface PDI or recombinant PDI and higher 
inhibitory effects on U46619- and/or collagen-induced platelet aggregation than 
juglone. The glycosylated derivatives 18 and 22 showed improved selectivity for 
inhibiting the proliferation of multiple myeloma RPMI 8226 cells, and the IC50 
values reached 61 and 48 nM, respectively, in a 72 h cell viability test. In 
addition, 18 and 22 were able to prevent tumor cell-induced platelet aggregation 
and platelet-enhanced tumor cell proliferation. The molecular docking showed the 
amino acid residues Gln243, Phe440, and Leu443 are important for the 
compound-protein interaction. Our results reveal the potential of juglone 
derivatives to serve as novel antiplatelet and anticancer dual agents, which are 
available to interrupt platelet-cancer interplay through covalent binding to PDI 
catalytic active site.

DOI: 10.1021/acs.jmedchem.3c02107
PMCID: PMC10945480
PMID: 38381886 [Indexed for MEDLINE]

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


2. Electromagn Biol Med. 2023 Oct 2;42(4):133-143. doi: 
10.1080/15368378.2023.2265935. Epub 2023 Dec 29.

The protective role of 5-hydroxy-1,4-naphthoquinone against the harmful effects 
of 50 Hz electric field in rat lung tissue.

Şenol N(1), Şahin M(2), Şahin U(3)(4).

Author information:
(1)Department of Nutrition and Dietetics, Faculty of Health Sciences, Süleyman 
Demirel University, Isparta, Türkiye.
(2)Department of Bioengineering, Institute of Science, Süleyman Demirel 
University, Isparta, Türkiye.
(3)Department of Chemistry, Faculty of Art and Science, University of Süleyman 
Demirel, Isparta, Türkiye.
(4)Genetic Research Unit, Innovative Technologies Application and Research 
Center, Süleyman Demirel University, Isparta, Türkiye.

There is strong scientific evidence that the electric field is harmful to life. 
Exposure to an electric field (EF) can cause lung toxicity and respiratory 
disorders. In addition, the electric field has been shown to cause tissue damage 
through inflammation and apoptosis. Juglone (JUG) is one of the powerful 
antioxidants with anti-apoptotic and anti-inflammatory, various pharmacological 
properties in the biological system. In this study, we evaluated the efficacy of 
JUG against the potential adverse effects of electric field on the lung. 
Twenty-four Wistar albino rats were randomly divided into three groups; control 
group (Cont), EF group, and EF exposure+JUG-treated group (EJUG). After routine 
histological procedures, sections stained with hematoxylin-eosin (H&E) showed 
significant changes in lung tissues in the EF group compared to the Cont group. 
Significant protective effects were observed in the building volumes and 
histopathology in the EJUG group. Our immunohistochemical and gene expression 
results increased the expression of caspase-3 and tumor necrosis factor alpha 
(TNF-α) in the EF group (p < 0.05). Juglon increased cytokine signal suppressor 
(SOCS) expression (p < 0.001). These findings were consistent with the 
antioxidant effect of JUG treatment. We reasoned that exposure to EF damaged rat 
lung tissues and administration of JUG alleviated the complications caused by 
50 Hz EF.

Plain Language Summary: Depending on technological developments, the use of 
electric devices and equipment is increasing day by day. During the transmission 
and use of electrical energy, electric and magnetic fields occurs. This forces 
can affect the environment and people. 50 Hz electric fields damage the cells 
and tissues of exposed living things in many ways. In our study, we examined the 
hypothesis that juglone, a natural antioxidant, can reduce the damage caused by 
the 50 Hz electric field that we are exposed to for a long time in our daily 
lives. In our study, it was shown by histological and genetic approaches that 
juglone, which has antioxidant and anti-apoptotic effects, may be protective 
against lung damage due to electric field exposure on experimental animals. 
According to our study results, for increased electric field exposure as a 
consequence of developing technology, juglone could be an important supportive 
treatment option.

DOI: 10.1080/15368378.2023.2265935
PMID: 37811636 [Indexed for MEDLINE]


3. Res Vet Sci. 2023 Nov;164:104987. doi: 10.1016/j.rvsc.2023.104987. Epub 2023
Aug  26.

Protective effect of juglone on electric field-induced apoptosis and 
inflammation in liver and kidney tissue in rats.

Şenol N(1), Şahin M(2), Şahin U(3).

Author information:
(1)Department of Nutrition and Dietetics, Faculty of Health Sciences, University 
of Süleyman Demirel, Isparta, Türkiye.
(2)Department of Bioengineering, Institute of Science, University of Süleyman 
Demirel, Isparta, Türkiye. Electronic address: meldasahin0510@gmail.com.
(3)Department of Chemistry, Faculty of Art and Science, University of Süleyman 
Demirel, Isparta, Türkiye; Genetic Research Unit, Innovative Technologies 
Application and Research Center, University of Süleyman Demirel, Isparta, 
Türkiye.

Electric field (EF) has been shown to cause tissue damage mainly through 
oxidative stress, inflammation, and apoptosis. Thus, juglone 
(5-hydroxy-1,4-naphthoquinone) (JUG), which has antioxidant and antiapoptotic 
properties, is thought to be effective against electric field-induced damage. We 
aimed to investigate whether 50 Hz alternating current (AC) triggers 
inflammation and apoptosis in rat liver and kidney tissues and evaluate the JUG 
supplement's estimated protective effect. Twenty-four adult male wistar albino 
rats were divided into control, EF and EF + JUG groups, each containing eight 
rats. The EF and EF + JUG groups were exposed to EF while no EF exposure and JUG 
were applied to the control group. At the end of the experiment, liver and 
kidney tissues were collected for histological (H&E, caspase-3 and TNF-α for 
immunohistochemical staining), and genetics (SOCS, caspase-3 and TNF-α, PCR 
analyses). After routine histological procedures, sections stained with H&E 
showed significant changes in liver and kidney tissues in the EF group compared 
to the control group (p < 0.05). Significant protective effects were observed in 
the building volumes and histopathology in the EF + JUG group (p < 0.05). Our 
gene expression results increased the expression of caspase-3 and TNF-α in the 
EF group (p < 0.001). Juglone increased SOCS expression (p < 0.001). These 
findings were consistent with the anti-apoptotic and anti-inflammatory effects 
of JUG treatment. We reasoned that exposure to EF damaged rat liver and kidney 
tissues and administration of JUG alleviated the complications caused by 50 Hz 
EF.

Copyright © 2023 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.rvsc.2023.104987
PMID: 37659348 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest No potential 
conflict of interest was reported by the author(s).


4. Eur J Med Chem. 2023 Apr 5;252:115304. doi: 10.1016/j.ejmech.2023.115304. Epub
 2023 Mar 24.

Molecular design, synthesis and anticancer activity of new 
thiopyrano[2,3-d]thiazoles based on 5-hydroxy-1,4-naphthoquinone (juglone).

Ivasechko I(1), Lozynskyi A(2), Senkiv J(1), Roszczenko P(3), Kozak Y(1), Finiuk 
N(1), Klyuchivska O(1), Kashchak N(1), Manko N(1), Maslyak Z(4), Lesyk D(2), 
Karkhut A(5), Polovkovych S(5), Czarnomysy R(6), Szewczyk O(6), Kozytskiy A(7), 
Karpenko O(8), Khyluk D(9), Gzella A(10), Bielawski K(6), Bielawska A(3), Dzubak 
P(11), Gurska S(11), Hajduch M(11), Stoika R(12), Lesyk R(13).

Author information:
(1)Institute of Cell Biology of National Academy of Sciences of Ukraine, 
Drahomanov14/16, Lviv, 79005, Ukraine.
(2)Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo 
Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine.
(3)Department of Biotechnology, Faculty of Pharmacy, Medical University of 
Bialystok, Jana Kilińskiego 1, 15-089, Bialystok, Poland.
(4)Institute of Blood Pathology and Transfusion Medicine of National Academy of 
Medical Sciences of Ukraine, General Chuprynky 45, Lviv, 79044, Ukraine.
(5)Department of Technology of Biologically Active Substances, Pharmacy and 
Biotechnology, Lviv Polytechnic National University, Bandera 12, Lviv, 79013, 
Ukraine.
(6)Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical 
University of Bialystok, Jana Kilińskiego 1, 15-089, Bialystok, Poland.
(7)Enamine Ltd, Chervonotkatska Street 78, Kyiv, 02094, Ukraine; L.V. 
Pysarzhevsky Institute of Physical Chemistry, National Academy of Sciences of 
Ukraine, Nauky Avenue 31, Kyiv, 03028, Ukraine.
(8)Enamine Ltd, Chervonotkatska Street 78, Kyiv, 02094, Ukraine.
(9)Department of Organic Chemistry, Faculty of Pharmacy with Medical Analytics 
Division, Medical University of Lublin, 4A Chodzki, Lublin, 20-093, Poland.
(10)Department of Organic Chemistry, Poznan University of Medical Sciences, 
Grunwaldzka 6, 60-780, Poznan, Poland.
(11)Institute of Molecular and Translational Medicine, Faculty of Medicine and 
Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 
77900, Olomouc, Czech Republic.
(12)Institute of Cell Biology of National Academy of Sciences of Ukraine, 
Drahomanov14/16, Lviv, 79005, Ukraine. Electronic address: 
stoika.rostyslav@gmail.com.
(13)Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo 
Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine; 
Department of Biotechnology and Cell Biology, Medical College, University of 
Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, 
Rzeszow, Poland. Electronic address: dr_r_lesyk@org.lviv.net.

A series of 11-substituted 
9-hydroxy-3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones 
3.1-3.13 were synthesized via hetero-Diels-Alder reaction of 
5-ene-4-thioxo-2-thiazolidinones and 5-hydroxy-1,4-naphthoquinone (juglone). The 
structure of newly synthesized compounds was established by means of spectral 
data and a single-crystal X-ray diffraction analysis. The synthesized compounds 
were tested on a panel of cell lines representing different types of cancer as 
well as normal and pseudonormal cells and peripheral human blood lymphocytes. 
Compound 3.10 was found to be the most active derivative, exhibiting a cytotoxic 
effect similar to doxorubicin's one (IC50 ranged from 0.6 to 5.98 μM), but less 
toxic to normal and pseudonormal cells. All synthesized compounds were able to 
interact with DNA, although their anticancer activity did not correlate with the 
potency of interaction with DNA. The status of p53 in colorectal cancer cells 
correlated with the activity of the synthesized derivatives 3.1, 3.7, and 3.10. 
Compound 3.10 did not have an acute toxic effect on the body of С57BL/6 mice, 
unlike the well-known anticancer drug doxorubicin, which was used as a positive 
control. The injection of 3.10 (20 mg/kg) to mice had no effect on the counts of 
leukocytes, erythrocytes, platelets and hemoglobin level in their blood, in 
contrast to doxorubicin, which caused anemia and leukopenia, indicating 
bio-tolerance of 3.10in vivo.

Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights 
reserved.

DOI: 10.1016/j.ejmech.2023.115304
PMID: 37001390 [Indexed for MEDLINE]

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.


5. Int Immunopharmacol. 2022 Dec;113(Pt A):109415. doi: 
10.1016/j.intimp.2022.109415. Epub 2022 Nov 9.

Juglone: "A novel immunomodulatory, antifibrotic, and schistosomicidal agent to 
ameliorate liver damage in murine schistosomiasis mansoni".

Khalil RG(1), Ibrahim AM(2), Bakery HH(3).

Author information:
(1)Immunology Division, Faculty of Science, Beni-Suef University, Egypt. 
Electronic address: rehab.khalil@science.bsu.edu.eg.
(2)Medical Malacology Department, Theodor Bilharz Research Institute, Giza, 
Egypt.
(3)Immunology Division, Faculty of Science, Beni-Suef University, Egypt.

Schistosomiasis remains one of the world's leading health concerns, affecting 
millions. The granulomatous reaction is the most significant immunopathological 
change associated with Schistosoma mansoni infection, resulting in significant 
mortality. Recent progress has been made in the search for new natural compounds 
to reduce schistosomiasis and its immunopathology. Walnuts contain the phenolic 
compound Juglone (5-hydroxy-1,4-naphthoquinone), which has antiparasitic, 
anti-inflammatory, immunoregulatory, and antioxidant properties. There were 
three groups of infected mice: untreated (IU), Juglone-treated (JUG T), and 
praziquantel-treated (PZ). In mice treated at 8 mg Juglone /kg body weight, a 
reduction of 63.1 % and 52.1 % were observed in the number of male and female 
worms, respectively. In addition, the number of eggs/g tissue was reduced by 
65.7 % in the liver, 58.58 % in the intestine, and 62.31 % in the liver and 
intestine combined. In addition, Juglone decreased hepatic granuloma size by 
55.1 % and collagen fiber deposition by 23.4 % compared to PZQ (41.18 % and 
11.2 %, respectively). Interestingly, the JUG T group had significantly lower 
levels of IL-4, IL-13, IL-37, TNF-α, TGF-β, and IFN-γ than PZ mice (p < 0.05). 
While IL-10 and IL-17 levels rose (p < 0.01), Juglone could restore hepatic ALT, 
AST, GGT, and LDH activities following infection. In addition, it increased 
catalase, SOD, GSH, and GST while decreasing NO and LPO in comparison to the 
infected group. Moreover, anti-SWAP, SEA, and CAP IgG levels increased 
significantly. IgE levels did not change significantly, however. Juglone could 
be used as an antifibrotic, immunomodulatory, and schistosomicidal agent; thus, 
it could be used in place of PZQ.

Copyright © 2022 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.intimp.2022.109415
PMID: 36461604 [Indexed for MEDLINE]

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.