Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. BMC Res Notes. 2023 Sep 11;16(1):202. doi: 10.1186/s13104-023-06489-7.

Effect of fenofibrate and selective PPARα modulator (SPPARMα), pemafibrate on 
KATP channel activity and insulin secretion.

Kitamura S(1)(2), Murao N(3), Yokota S(1), Shimizu M(1)(4), Ono T(1), Seino 
Y(3), Suzuki A(3), Maejima Y(1), Shimomura K(5).

Author information:
(1)Department of Bioregulation and Pharmacological Medicine, Fukushima Medical 
University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
(2)Department of Plastic and Reconstructive Surgery, Fukushima Medical 
University School of Medicine, Fukushima, Japan.
(3)Department of Endocrinology, Diabetes and Metabolism, Fujita Health 
University, Toyoake, Japan.
(4)Department of Neurology, Matsumura General Hospital, Iwaki, Japan.
(5)Department of Bioregulation and Pharmacological Medicine, Fukushima Medical 
University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan. 
shimomur@fmu.ac.jp.

OBJECTIVE: Insulin secretion is regulated by ATP-sensitive potassium (KATP) 
channels in pancreatic beta-cells. Peroxisome proliferator-activated receptors 
(PPAR) α ligands are clinically used to treat dyslipidemia. A PPARα ligand, 
fenofibrate, and PPARγ ligands troglitazone and 15-deoxy-∆12,14-prostaglandin J2 
are known to close KATP channels and induce insulin secretion. The recently 
developed PPARα ligand, pemafibrate, became a new entry for treating 
dyslipidemia. Because pemafibrate is reported to improve glucose intolerance in 
mice treated with a high fat diet and a novel selective PPARα modulator, it may 
affect KATP channels or insulin secretion.
RESULTS: The effect of fenofibrate (100 µM) and pemafibrate (100 µM) on insulin 
secretion from MIN6 cells was measured by using batch incubation for 10 and 
60 min in low (2 mM) and high (10 mM) glucose conditions. The application of 
fenofibrate for 10 min significantly increased insulin secretion in low glucose 
conditions. Pemafibrate failed to increase insulin secretion in all of the 
conditions experimented in this study. The KATP channel activity was measured by 
using whole-cell patch clamp technique. Although fenofibrate (100 µM) reduced 
the KATP channel current, the same concentration of pemafibrate had no effect. 
Both fenofibrate and pemafibrate had no effect on insulin mRNA expression.

© 2023. BioMed Central Ltd., part of Springer Nature.

DOI: 10.1186/s13104-023-06489-7
PMCID: PMC10494450
PMID: 37697384 [Indexed for MEDLINE]

Conflict of interest statement: There are no competing interests.


2. Metabolites. 2022 May 30;12(6):495. doi: 10.3390/metabo12060495.

Identification of Serum Oxylipins Associated with the Development of Coronary 
Artery Disease: A Nested Case-Control Study.

Chiang KM(1), Chen JF(2), Yang CA(3), Xiu L(4), Yang HC(5), Shyur LF(6), Pan 
WH(1)(2)(3)(4).

Author information:
(1)Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
(2)Institute of Public Health, School of Medicine, National Yang-Ming Chiao Tung 
University, Taipei 11221, Taiwan.
(3)Department of Biochemical Science and Technology, National Taiwan University, 
Taipei 10617, Taiwan.
(4)Institute of Population Health Sciences, National Health Research Institutes, 
Miaoli 35053, Taiwan.
(5)Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan.
(6)Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, 
Taiwan.

Coronary artery disease (CAD) is among the leading causes of death globally. The 
American Heart Association recommends that people should consume more PUFA-rich 
plant foods to replace SFA-rich ones to lower serum cholesterol and prevent CAD. 
However, PUFA may be susceptible to oxidation and generate oxidized products 
such as oxylipins. In this study, we investigated whether the blood oxylipin 
profile is associated with the risk of developing CAD and whether including 
identified oxylipins may improve the predictability of CAD risk. We designed a 
nested case-control study with 77 cases and 148 matched controls from a 10-year 
follow-up of the Nutrition and Health Survey in a Taiwanese cohort of 720 people 
aged 50 to 70. A panel of 46 oxylipins was measured for baseline serum samples. 
We discovered four oxylipins associated with CAD risk. 13-oxo-ODE, which has 
been previously found in formed plagues, was positively associated with CAD (OR 
= 5.02, 95%CI = 0.85 to 15.6). PGE2/PGD2, previously shown to increase cardiac 
output, was inversely associated (OR = 0.16, 95%CI = 0.06 to 0.42). 
15-deoxy-PGJ2, with anti-inflammatory and anti-apoptosis effects on 
cardiomyocytes (OR = 0.26, 95%CI = 0.09 to 0.76), and 5-HETE, which was 
associated with inflammation (OR = 0.28, 95%CI = 0.10 to 0.78), were also 
negatively associated as protective factors. Adding these four oxylipins to the 
traditional risk prediction model significantly improved CAD prediction.

DOI: 10.3390/metabo12060495
PMCID: PMC9231201
PMID: 35736428

Conflict of interest statement: The authors declare no competing financial or 
non-financial interests.


3. Redox Biol. 2021 Oct;46:102103. doi: 10.1016/j.redox.2021.102103. Epub 2021
Aug  13.

Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 
activation in endothelial cells: Amplification of low shear stress signaling by 
primary cilia.

Ishii T(1), Warabi E(2), Mann GE(3).

Author information:
(1)School of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8577, Japan. 
Electronic address: ishiitetsuro305@gmail.com.
(2)School of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8577, Japan. 
Electronic address: warabi-e@md.tsukuba.ac.jp.
(3)King's British Heart Foundation Centre of Research Excellence, School of 
Cardiovascular Medicine & Sciences, King's College London, 150 Stamford Street, 
London, SE1 9NH, UK. Electronic address: giovanni.mann@kcl.ac.uk.

Endothelial cells are sensitive to mechanical stress and respond differently to 
oscillatory flow versus unidirectional flow. This review highlights the 
mechanisms by which a wide range of unidirectional laminar shear stress induces 
activation of the redox sensitive antioxidant transcription factor nuclear 
factor-E2-related factor 2 (Nrf2) in cultured endothelial cells. We propose that 
fibroblast growth factor-2 (FGF-2), brain-derived neurotrophic factor (BDNF) and 
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) are potential Nrf2 activators 
induced by laminar shear stress. Shear stress-dependent secretion of FGF-2 and 
its receptor-mediated signaling is tightly controlled, requiring neutrophil 
elastase released by shear stress, αvβ3 integrin and the cell surface 
glycocalyx. We speculate that primary cilia respond to low laminar shear stress 
(<10 dyn/cm2), resulting in secretion of insulin-like growth factor 1 (IGF-1), 
which facilitates αvβ3 integrin-dependent FGF-2 secretion. Shear stress induces 
generation of heparan-binding epidermal growth factor-like growth factor 
(HB-EGF), which contributes to FGF-2 secretion and gene expression. Furthermore, 
HB-EGF signaling modulates FGF-2-mediated NADPH oxidase 1 activation that favors 
casein kinase 2 (CK2)-mediated phosphorylation/activation of Nrf2 associated 
with caveolin 1 in caveolae. Higher shear stress (>15 dyn/cm2) induces vesicular 
exocytosis of BDNF from endothelial cells, and we propose that BDNF via the 
p75NTR receptor could induce CK2-mediated Nrf2 activation. Unidirectional 
laminar shear stress upregulates gene expression of FGF-2 and BDNF and 
generation of 15d-PGJ2, which cooperate in sustaining Nrf2 activation to protect 
endothelial cells against oxidative damage.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

DOI: 10.1016/j.redox.2021.102103
PMCID: PMC8379703
PMID: 34425388 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that there are no conflicts 
of interest regarding the publication of this article.


4. Biomed Mater. 2021 Apr 1;16(4):045008. doi: 10.1088/1748-605X/abee61.

Regeneration potential of decellularized periodontal ligament cell sheets 
combined with 15-deoxy-Δ(12,14)-prostaglandin J(2) nanoparticles in a rat 
periodontal defect.

Jiang Y(1), Liu JM, Huang JP, Lu KX, Sun WL, Tan JY, Li BX, Chen LL, Wu YM.

Author information:
(1)Department of Periodontology, The Second Affiliated Hospital of Zhejiang 
University School of Medicine, Hangzhou, People's Republic of China. Key 
Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University 
School of Stomatology, Hangzhou, People's Republic of China.

Periodontitis is a chronic inflammatory disease characterized by loss of 
attachment and destruction of the periodontium. Decellularized sheet, as an 
advanced tissue regeneration engineering biomaterial, has been researched and 
applied in many fields, but its effects on periodontal regeneration remain 
unclear. In this study, the biological properties of decellularized human 
periodontal ligament cell (dHPDLC) sheets were evaluated in vitro. 
Polycaprolactone/gelatin (PCL/GE) nanofibers were fabricated as a carrier to 
enhance the mechanical strength of the dHPDLC sheet. 15-deoxy-[Formula: see 
text]-prostaglandin J2 (15d-PGJ2) nanoparticles were added for anti-inflammation 
and regeneration improvement. For in vivo analysis, dHPDLC sheets combined with 
15d-PGJ2 nanoparticles, with or without PCL/GE, were implanted into rat 
periodontal defects. The periodontal regeneration effects were identified by 
microcomputed tomography (micro-CT) and histological staining, and 
immunohistochemistry. The results revealed that DNA content was reduced by 
96.6%. The hepatocyte growth factor, vascular endothelial growth factor, and 
basic fibroblast growth factor were preserved but reduced. The expressions or 
distribution of collagen I and fibronectin were similar in dHPDLC and 
nondecellularized cell sheets. The dHPDLC sheets maintained the intact structure 
of the extracellular matrix. It could be recellularized by allogeneic human 
periodontal stem ligament cells and retain osteoinductive potential. Newly 
formed bone, cementum, and PDL were observed in dHPDLC sheets combined with 
15d-PGJ2 groups, with or without PCL/GE nanofibers, for four weeks 
post-operation in vivo. Bringing together all these points, this new construct 
of dHPDLC sheets can be a potential candidate for periodontal regeneration in an 
inflammatory environment of the oral cavity.

DOI: 10.1088/1748-605X/abee61
PMID: 33793422 [Indexed for MEDLINE]


5. Brain Behav. 2020 Dec;10(12):e01866. doi: 10.1002/brb3.1866. Epub 2020 Nov 16.

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the 
neurotoxicity of 15-deoxy-Δ(12,14) -prostaglandin J(2).

Koma H(1), Yamamoto Y(1), Okamura N(2), Yagami T(1).

Author information:
(1)Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
(2)School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, 
Japan.

INTRODUCTION: 15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ) causes neuronal 
apoptosis independently of its nuclear receptor, peroxysome-proliferator 
activated receptor γ. Its membrane receptor, chemoattractant receptor-homologous 
molecule expressed on Th2 cells (CRTH2), did not also mediate the neurotoxicity 
of 15d-PGJ2 . In the present study, we ascertained whether membrane targets 
beside CRTH2 were involved in the neurotoxicity of 15d-PGJ2 .
METHODS: Neuronal membrane targets for 15d-PGJ2 were separated by 
two-dimensional electrophoresis, identified by proteomic approach. Their 
localizations were detected by microscopic immunofluorescence study. Cell 
viability and apoptosis was evaluated by MTT-reducing activity and caspase-3 
activity, respectively.
RESULTS: Voltage-dependent anion channel 1 (VDAC1) was identified as one of 
membrane targets for 15d-PGJ2 . Modification of VDAC1 with 15d-PGJ2 was detected 
by pull-down assay. VDAC1 was detected in the plasma membrane and localized on 
the neuronal cell surface. VDAC1 was partially colocalized with membrane targets 
for 15d-PGJ2 . The anti-VDAC antibody significantly attenuated the neurotoxicity 
of 15d-PGJ2 , accompanied by the suppression of the 15d-PGJ2 -stimulated 
caspase-3.
CONCLUSION: These findings suggested that the plasmalemmal VDAC might be 
involved in the neurotoxicity of 15d-PGJ2 .

© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

DOI: 10.1002/brb3.1866
PMCID: PMC7749624
PMID: 33200588 [Indexed for MEDLINE]

Conflict of interest statement: There is no conflict of interest.