Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Eur J Pharmacol. 2024 Oct 15;981:176883. doi: 10.1016/j.ejphar.2024.176883.
Epub  2024 Aug 10.

Glaucine inhibits hypoxia-induced angiogenesis and attenuates LPS-induced 
inflammation in human retinal pigment epithelial ARPE-19 cells.

Chen TE(1), Lo J(2), Huang SP(3), Chang KC(4), Liu PL(5), Wu HE(6), Chen YR(6), 
Chang YC(7), Liu CC(8), Lee PY(9), Lai YH(9), Wu PC(2), Wang SC(10), Li CY(11).

Author information:
(1)School of Medicine, College of Medicine, Kaohsiung Medical University, 
Kaohsiung, 80708, Taiwan.
(2)Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung 
Medical University, Kaohsiung, 80708, Taiwan; Department of Ophthalmology, 
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of 
Medicine, Kaohsiung, 83301, Taiwan.
(3)Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung 
Medical University, Kaohsiung, 80708, Taiwan; Department of Urology, Kaohsiung 
Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, 
Taiwan; Department of Urology, School of Medicine, College of Medicine, 
Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Institute of Medical 
Science and Technology, College of Medicine, National Sun Yat-Sen University, 
Kaohsiung 80424, Taiwan.
(4)Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, 
University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA; 
Department of Neurobiology, Center of Neuroscience, University of Pittsburgh 
School of Medicine, Pitts-burgh, PA, 15213, USA.
(5)Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical 
University, Kaohsiung, 80708, Taiwan.
(6)Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
University, Kaohsiung, 80708, Taiwan.
(7)Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
University, Kaohsiung, 80708, Taiwan; Department of Ophthalmology, School of 
Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, 
Taiwan.
(8)Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
University, Kaohsiung, 80708, Taiwan; Department of Ophthalmology, Chi Mei 
Medical Center, Tainan 71004, Taiwan.
(9)Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
University, Kaohsiung, 80708, Taiwan; Department of Ophthalmology, Kaohsiung 
Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, 
Taiwan.
(10)Department of Medical Laboratory Science and Biotechnology, Kaohsiung 
Medical University, Kaohsiung, 80708, Taiwan; Department of Medical Research, 
Kaohsiung Medical University Hospital, Kaohsiung, 80756, Taiwan. Electronic 
address: shuchiwang@kmu.edu.tw.
(11)Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
University, Kaohsiung, 80708, Taiwan; Department of Medical Research, Kaohsiung 
Medical University Hospital, Kaohsiung, 80756, Taiwan. Electronic address: 
chiayangli@kmu.edu.tw.

Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and 
anti-cancer activities. However, the effects of glaucine in the regulation of 
age-related macular degeneration (AMD) remain unclear. Herein, we aimed to 
investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in 
ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, 
methyl ester (DMOG) and cobalt chloride (CoCl2) for induction of hypoxia, while 
lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory 
response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 
5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible 
factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by 
Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte 
chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent 
assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for 
tube formation analysis. Expression of HIF-1α and secretion of VEGF were 
significantly increased under DMOG and CoCl2 induction, whereas glaucine 
significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and 
CoCl2-induced ARPE-19 cells. In addition, glaucine suppressed the tube formation 
by DMOG- and CoCl2-induced HUVEC cells. Moreover, glaucine also attenuated the 
production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated 
that glaucine exhibited anti-angiogenic and anti-inflammatory effects, 
suggesting that glaucine might have benefits for the treatment of AMD.

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

DOI: 10.1016/j.ejphar.2024.176883
PMID: 39128809 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare no conflict of interest.


2. Antioxidants (Basel). 2024 May 25;13(6):643. doi: 10.3390/antiox13060643.

Exploring Chemical Composition, Antioxidant, Enzyme Inhibitory and Cytotoxic 
Properties of Glaucium acutidentatum Hausskn. & Bornm. from Turkey Flora: A 
Novel Source of Bioactive Agents to Design Functional Applications.

Yagi S(1)(2), Zengin G(3), Uba AI(4), Maciejewska-Turska M(5), Sieniawska E(6), 
Świątek Ł(7), Rajtar B(7), Bahşi M(8), Guler O(9), Dall'Acqua S(10), 
Polz-Dacewicz M(7).

Author information:
(1)Department of Botany, Faculty of Science, University of Khartoum, Khartoum 
11115, Sudan.
(2)LAE, INRAE, Université de Lorraine, F-54000 Nancy, France.
(3)Physiology and Biochemistry Laboratory, Department of Biology, Science 
Faculty, Selcuk University, Konya 42130, Turkey.
(4)Department of Molecular Biology and Genetics, Istanbul AREL University, 
Istanbul 34537, Turkey.
(5)Department of Pharmacognosy with Medicinal Plant Garden, Medical University 
of Lublin, 20-093 Lublin, Poland.
(6)Department of Natural Products Chemistry, Medical University of Lublin, 
20-093 Lublin, Poland.
(7)Department of Virology with Viral Diagnostics Laboratory, Medical University 
of Lublin, 20-093 Lublin, Poland.
(8)Department of Primary Education, Faculty of Education, Fırat University, 
Elazıg 23119, Turkey.
(9)Pertek Sakine Genç Vocational School, Munzur University, Tunceli 62500, 
Turkey.
(10)Department of Pharmaceutical and Pharmacological Sciences, University of 
Padova, 35131 Padua, Italy.

The present study was performed to determine the chemical constituents, 
cytotoxicity, antioxidant and enzyme inhibition activities of the aerial parts 
of Glaucium acutidentatum Hausskn. and Bornm. (family Papaveraceae). Methanolic 
and aqueous extracts were prepared by maceration, homogenizer-assisted 
extraction (HAE) and infusion. Results showed that the highest total phenolic 
and flavonoids contents were obtained from the methanol extracts obtained by HAE 
(53.22 ± 0.10 mg GAE/g) and maceration (30.28 ± 0.51 mg RE/g), respectively. The 
aporphine, beznyltetrahydroisoquinoline, and protopine types of Glaucium 
alkaloids have been tentatively identified. Among them, glaucine was identified 
in all extracts. Flavonoids, phenolic acids, coumarins, organic acids and fatty 
acids were also detected. Methanolic extract obtained using the HAE method 
displayed the highest anti-DPPH (41.42 ± 0.62 mg TE/g), total antioxidant (1.20 
± 0.17 mmol TE/g), Cu2+ (113.55 ± 6.44 mg TE/g), and Fe3+ (74.52 ± 4.74 mg TE/g) 
reducing properties. The aqueous extracts obtained by infusion and HAE methods 
exerted the best anti-ABTS (103.59 ± 1.49 mg TE/g) and chelating (19.81 ± 0.05 
mg EDTAE/g) activities, respectively. Methanolic extract from HAE recorded the 
highest acetylcholinesterase (2.55 ± 0.10 mg GALAE/g) and α-amylase (0.51 ± 0.02 
mmol ACAE/g) inhibition activities, while that obtained by maceration showed the 
best butyrylcholinesterase (3.76 ± 0.31 mg GALAE/g) inhibition activity. Both 
extracts revealed the best tyrosinase inhibitory activity (25.15 ± 1.00 and 
26.79 ± 2.36 mg KAE/g, p ≥ 0.05). G. acutidentatum maceration-derived aqueous 
extract showed selective anticancer activity against cells originating from 
human hypopharyngeal carcinoma. In conclusion, these findings indicated that G. 
acutidentatum is a promising source of alkaloids and phenolic compounds for 
variable pharmaceutical formulations.

DOI: 10.3390/antiox13060643
PMCID: PMC11200578
PMID: 38929082

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


3. Chem Biodivers. 2024 Apr;21(4):e202301865. doi: 10.1002/cbdv.202301865. Epub 
2024 Mar 15.

Variability of Isoquinoline Alkaloid Profiles and Anticholinesterase Activities 
with Binding-Mode Predictions of Glaucium flavum Population.

Bozkurt B(1), Ulkar D(1), Nurlu N(1), Coban G(2), Gumus ZP(3), Unver-Somer N(1).

Author information:
(1)Department of Pharmacognosy, Faculty of Pharmacy, Ege University, 35100, 
Bornova, Izmir, Türkiye.
(2)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, 
35100, Bornova, Izmir, Türkiye.
(3)Ege University, Central Research Test and Analysis Laboratory Application and 
Research Center (EGE-MATAL), Ege University, 35100, Bornova, Izmir, Türkiye.

In this study, phytochemical and biological activity studies supported by 
docking were carried out on a species of the genus Glaucium, a repository of 
isoquinoline alkaloids. The GC-MS (Gas Chromatography-Mass Spectrometry) method 
is used to characterize the isoquinoline alkaloids of Glaucium flavum Crantz. 
(Papaveraceae). G. flavum was collected from seven different regions of Türkiye 
(Antalya, Urla-Izmir, Mordogan-Izmir, Mugla, Assos-Canakkale, 
Karabiga-Canakkale, Giresun) and totally 17 compounds were detected by GC-MS. 
Glaucine was found to be the major constituent in the sample collected from 
Mugla, whereas isocorydine was recorded to be the principal alkaloid in other 
samples. Further fractionation studies on G. flavum collected from Antalya 
province in Southwestern Türkiye, yielded five major alkaloids (isocorydine 1, 
dihydrosanguinarine 2, glaucine 3, dehydroglaucine 4, protopine 5) which were 
characterized by spectroscopic methods. Anticholinesterase activities of the 
extracts and isolated alkaloids were also tested by in vitro Ellman method. The 
isolated compounds were also analyzed by a molecular docking technique to 
determine the binding orientations in the gorge of the active site of 
acetylcholinesterase (AChE) and a homology model of butyrylcholinesterase 
(BuChE). This is the first comparative investigation of the phytochemical 
composition and biodiversity of Glaucium flavum species growing in Türkiye.

© 2024 Wiley‐VHCA AG, Zurich, Switzerland.

DOI: 10.1002/cbdv.202301865
PMID: 38415909 [Indexed for MEDLINE]


4. J Biomol Struct Dyn. 2024 Feb 20:1-17. doi: 10.1080/07391102.2023.2294165. 
Online ahead of print.

Integrating network pharmacology, molecular docking and simulation approaches 
with machine learning reveals the multi-target pharmacological mechanism of 
Berberis integerrima against diabetic nephropathy.

Zhang X(1), Chao P(2), Zhang L(3), Lu J(4), Yang A(5), Jiang H(6), Lu C(1).

Author information:
(1)Department of Nephrology, The First Affiliated Hospital of Xinjiang Medical 
University, Urumqi, China.
(2)Department of Cardiology, People's Hospital of Xinjiang Uygur Autonomous 
Region, Urumqi, China.
(3)Department of Endocrine, People's Hospital of Xinjiang Uygur Autonomous 
Region, Urumqi, China.
(4)Xinjiang Medical University, Urumqi, China.
(5)Department of Traditional Chinese Medicine, People's Hospital of Xinjiang 
Uygur Autonomous Region, Urumqi, China.
(6)Department of Nephrology, People's Hospital of Xinjiang Uygur Autonomous 
Region, Urumqi, China.

Diabetic nephropathy (DN) is one of the most feared complications of diabetes 
and key cause of end-stage renal disease (ESRD). Berberis integerrima has been 
widely used to treat diabetic complications, but exact molecular mechanism is 
yet to be discovered. Data on active ingredients of B. integerrima and target 
genes of both diabetic nephropathy and B.integerrima were obtained from public 
databases. Common results between B. integerrima and DN targets were used to 
create protein-protein interaction (PPI) network using STRING database and 
exported to Cytoscape software for the selection of hub genes based on degree of 
connectivity. Future, PPI network between constituents and overlapping targets 
was created using Cytoscape to investigate the network pharmacological effects 
of B. integerrima on DN. KEGG pathway analysis of core genes exposed their 
involvement in excess glucose-activated signaling pathway. Then, expression of 
core genes was validated through machine learning classifiers. Finally, PyRx and 
AMBER18 software was used for molecular docking and simulation. We found that 
Armepavine, Berberine, Glaucine, Magnoflorine, Reticuline, Quercetin inhibits 
the growth of diabetic nephropathy by affecting ICAM1, PRKCB, IKBKB, KDR, ALOX5, 
VCAM1, SYK, TBXA2R, LCK, and F3 genes. Machine learning revealed SYK and PRKCB 
as potential genes that could use as diagnostic biomarkers against DN. 
Furthermore, docking and simulation analysis showed the binding affinity and 
stability of the active compound with target genes. Our study revealed that B. 
integerrima has preventive effect on DN by acting on glucose-activated signaling 
pathways. However, experimental studies are needed to reveal biosafety profiles 
of B. integerrima in DN.Communicated by Ramaswamy H. Sarma.

DOI: 10.1080/07391102.2023.2294165
PMID: 38379386


5. Biomed Pharmacother. 2023 Nov;167:115511. doi: 10.1016/j.biopha.2023.115511. 
Epub 2023 Sep 18.

The composition, pharmacological effects, related mechanisms and drug delivery 
of alkaloids from Corydalis yanhusuo.

Feng JH(1), Chen K(2), Shen SY(3), Luo YF(3), Liu XH(4), Chen X(5), Gao W(3), 
Tong YR(6).

Author information:
(1)School of Basic Medical Sciences, Capital Medical University, Beijing 100069, 
China; School of Pharmaceutical Sciences, Capital Medical University, Beijing 
100069, China.
(2)National Resource Center for Chinese Materia Medica, China Academy of Chinese 
Medical Sciences, Beijing 100700, China.
(3)School of Traditional Chinese Medicine, Capital Medical University, Beijing 
100069, China.
(4)School of Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, 
China.
(5)School of Basic Medical Sciences, Capital Medical University, Beijing 100069, 
China.
(6)School of Pharmaceutical Sciences, Capital Medical University, Beijing 
100069, China. Electronic address: tongyuru@ccmu.edu.cn.

Corydalis yanhusuo W. T. Wang, also known as yanhusuo, yuanhu, yanhu and xuanhu, 
is one of the herb components of many Chinese Traditional Medicine prescriptions 
such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was 
traditionally used to relieve pain and motivate blood and Qi circulation. Now 
there has been growing interest in pharmacological effects of alkaloids, the 
main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. 
yanhusuo are its important bioactive components and can be characterized into 
protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and 
proper extraction or co-administration methods modulate their contents and 
efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the 
nervous system, cardiovascular system, cancer and others through multiple 
molecular mechanisms such as modulating neurotransmitters, ion channels, gut 
microbiota, HPA axis and signaling pathways and are potential treatments for 
many diseases. Plenty of novel drug delivery methods such as autologous red 
blood cells, self-microemulsifying drug delivery systems, nanoparticles and 
others have also been investigated to better exert the effects of alkaloids from 
C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo, 
their pharmacological effects and mechanisms, and methods of drug delivery to 
lay a foundation for future investigations.

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

DOI: 10.1016/j.biopha.2023.115511
PMID: 37729733

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.