Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Placenta. 2020 Oct;100:45-53. doi: 10.1016/j.placenta.2020.08.009. Epub 2020
Aug  11.

Placental distribution of endogenous and exogenous substances: A pilot study 
utilizing cryo-sampled specimen off delivery room.

Li ZM(1), Benker B(2), Bao Q(3), Henkelmann B(4), Corsten C(4), Michalke B(2), 
Pauluschke-Fröhlich J(5), Flisikowski K(6), Schramm KW(7), De Angelis M(8).

Author information:
(1)Helmholtz Zentrum München-German Research Center for Environmental Health 
(GmbH), Molecular EXposomics, Ingolstädter Landstr. 1, 85764, Neuherberg, 
Germany; School of Life Sciences Weihenstephan (Nutrition), Technische 
Universität München, 85354, Freising, Germany. Electronic address: 
zhong-min.li@helmholtz-muenchen.de.
(2)Helmholtz Zentrum München-German Research Center for Environmental Health 
(GmbH), Research Unit Analytical BioGeoChemistry, Ingolstädter Landstr. 1, 
85764, Neuherberg, Germany.
(3)Ningbo College of Health Sciences, 315100, Ningbo, Zhejiang, China.
(4)Helmholtz Zentrum München-German Research Center for Environmental Health 
(GmbH), Molecular EXposomics, Ingolstädter Landstr. 1, 85764, Neuherberg, 
Germany.
(5)Department für Frauengesundheit Universitäts-Frauenklinik Tübingen, 
Calwerstr. 7, 70276, Tübingen, Germany.
(6)Lehrstuhl für Biotechnologie der Nutztiere, Technische Universität München, 
Liesel-Beckmannstr. 1, 85354, Freising, Germany.
(7)Helmholtz Zentrum München-German Research Center for Environmental Health 
(GmbH), Molecular EXposomics, Ingolstädter Landstr. 1, 85764, Neuherberg, 
Germany; Department für Biowissenschaftliche Grundlagen, Technische Universität 
München, Weihenstephaner Steig 23, 85350, Freising, Germany.
(8)Helmholtz Zentrum München-German Research Center for Environmental Health 
(GmbH), Molecular EXposomics, Ingolstädter Landstr. 1, 85764, Neuherberg, 
Germany. Electronic address: meri.deangelis@helmholtz-muenchen.de.

INTRODUCTION: Reliability in the use of placentome (including placenta, 
umbilical cord, and cord blood) biomarkers requires an understanding of their 
distributions. Here we aim to develop a simple and proper placenta sampling 
scheme, and to evaluate the placental distributions of biomarkers.
METHODS: We developed a continuous cooling chain protocol off delivery room and 
cryo-subsampling method for placenta sampling. The levels of thyroid hormones 
(THs), elements, persistent organic pollutants (POPs), monoamines, and vitamin E 
were measured using UPLC-Q-TOF-MS, HPLC-ICP-MS, HPLC-EcD, and HRGC-HRMS, 
respectively. The distributions of biomarkers were assessed.
RESULTS: In human placentome, l-thyroxine (T4), Cd, Se, Zn, Cu, Fe, Ca, K, Mg, 
α-tocopherol, β-tocopherol, and β-tocotrienol levels were higher in placenta 
than in umbilical cord, while Pb and Mn were concentrated in human cord. In 
porcine placentome, T4, 3,3',5'-triiodo-l-thyronine (rT3), 
3,3'-diiodo-l-thyronine, Cd, Pb, Zn, K, and Al levels were higher in the cord. 
The intraclass correlation coefficient (ICC) was <0.4 for 
3,3',5-triiodo-l-thyronine, rT3, α-tocopherol, and 7 elements in human basal 
plate, indicating low reliability. rT3, Cd, Zn, Mn, and Cu were significantly 
concentrated in the central region in human placenta, while higher levels of As, 
Cd, Cr, and Al were found in the periphery region in porcine placenta. 
Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) 
showed moderate reliability (ICC: 0.40-0.98) except PCB-81, -126, and BDE-208, 
while polychlorinated dibenzo-p-doixins/furans (PCDD/Fs) showed poor reliability 
(ICC: 0.07-0.31).
DISCUSSION: These results highlight the complexity of placenta sampling. This 
study provides a novel and simple sampling approach in investigating placental 
exposomics.

Copyright © 2020 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.placenta.2020.08.009
PMID: 32828006 [Indexed for MEDLINE]


2. J Med Chem. 2018 Sep 27;61(18):8417-8443. doi: 10.1021/acs.jmedchem.8b00959. 
Epub 2018 Sep 14.

Discovery of ( S)-3-(3-(3,5-Dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( 
R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic 
Acid, a Nonpeptidic α(v)β(6) Integrin Inhibitor for the Inhaled Treatment of 
Idiopathic Pulmonary Fibrosis.

Procopiou PA, Anderson NA, Barrett J, Barrett TN, Crawford MHJ, Fallon BJ, 
Hancock AP, Le J, Lemma S, Marshall RP, Morrell J, Pritchard JM, Rowedder JE, 
Saklatvala P, Slack RJ, Sollis SL, Suckling CJ(1), Thorp LR, Vitulli G, 
Macdonald SJF.

Author information:
(1)Department of Pure & Applied Chemistry , University of Strathclyde , 295 
Cathedral Street , Glasgow G1 1XL , Scotland, U.K.

A series of 3-aryl(pyrrolidin-1-yl)butanoic acids were synthesized using a 
diastereoselective route, via a rhodium catalyzed asymmetric 1,4-addition of 
arylboronic acids in the presence of ( R)-BINAP to a crotonate ester to provide 
the ( S) absolute configuration for the major product. A variety of aryl 
substituents including morpholine, pyrazole, triazole, imidazole, and cyclic 
ether were screened in cell adhesion assays for affinity against αvβ1, αvβ3, 
αvβ5, αvβ6, and αvβ8 integrins. Numerous analogs with high affinity and 
selectivity for the αvβ6 integrin were identified. The analog ( 
S)-3-(3-(3,5-dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( 
R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic 
acid hydrochloride salt was found to have very high affinity for αvβ6 integrin 
in a radioligand binding assay (p Ki = 11), a long dissociation half-life (7 h), 
very high solubility in saline at pH 7 (>71 mg/mL), and pharmacokinetic 
properties commensurate with inhaled dosing by nebulization. It was selected for 
further clinical investigation as a potential therapeutic agent for the 
treatment of idiopathic pulmonary fibrosis.

DOI: 10.1021/acs.jmedchem.8b00959
PMID: 30215258 [Indexed for MEDLINE]


3. Eur J Nutr. 2016 Apr;55(3):1235-44. doi: 10.1007/s00394-015-0936-8. Epub 2015 
Jun 5.

Comparison of plasma alkylresorcinols (AR) and urinary AR metabolites as 
biomarkers of compliance in a short-term, whole-grain intervention study.

McKeown NM(1)(2), Marklund M(3), Ma J(4), Ross AB(5), Lichtenstein AH(4)(6), 
Livingston KA(4), Jacques PF(4)(6), Rasmussen HM(4)(6), Blumberg JB(4)(6), Chen 
CY(4)(6).

Author information:
(1)Jean Mayer U.S. Department of Agriculture (USDA) Human Nutrition Research 
Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, 
USA. nicola.mckeown@tufts.edu.
(2)Friedman School of Nutrition Science and Policy, Tufts University, Boston, 
MA, USA. nicola.mckeown@tufts.edu.
(3)Department of Public Health and Caring Sciences, Clinical Nutrition and 
Metabolism, Uppsala University, Uppsala, Sweden.
(4)Jean Mayer U.S. Department of Agriculture (USDA) Human Nutrition Research 
Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111, 
USA.
(5)Food and Nutritional Sciences, Department of Life Science Engineering, 
Chalmers University of Technology, Gothenburg, Sweden.
(6)Friedman School of Nutrition Science and Policy, Tufts University, Boston, 
MA, USA.

PURPOSE: Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat 
and rye. Plasma AR and their urinary metabolites may be suitable biomarkers of 
whole-grain (WG) wheat and rye consumption. The objective of this study was to 
examine plasma AR and urinary AR metabolites in response to WG wheat 
consumption.
METHODS: In a randomized crossover study, 19 subjects (10 males, 9 females; BMI 
22.0 kg/m(2); age 26 years) incorporated either 3 servings (48 g) or 6 servings 
(96 g) of WG wheat daily into their regular diet for 1 week. Subjects completed 
a 2-week washout period, abstaining from all WG consumption, before each 
intervention. Fasting blood and 24-h urine were collected before and after each 
intervention. Plasma AR homologues (C19:0, C21:0, C23:0) were quantified by 
GC-MS after diethyl ether and solid phase extraction and derivatization. Urinary 
AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-propanoic 
acid] were determined using HPLC with electrochemical detection after enzymatic 
deconjugation and ethyl acetate extraction.
RESULTS: Urinary total AR metabolites were significantly higher after 6 compared 
with 3 servings of WG wheat (56 vs. 32 μmol/day, P < 0.001). This dose-response 
relationship was independent of age, sex, energy intake, and baseline urinary AR 
metabolite concentration. Plasma total AR tended to be higher after 6 compared 
with 3 servings of WG wheat (103.0 vs. 86.9 nmol/L), but this difference was not 
significant (P = 0.42).
CONCLUSION: The results suggest that urinary AR metabolites from 24-h urine 
collections may be useful as biomarkers of compliance in intervention studies of 
WG wheat.

DOI: 10.1007/s00394-015-0936-8
PMID: 26043861 [Indexed for MEDLINE]


4. Ecotoxicol Environ Saf. 2015 Feb;112:7-14. doi: 10.1016/j.ecoenv.2014.10.004. 
Epub 2014 Nov 4.

Relative developmental toxicities of pentachloroanisole and pentachlorophenol in 
a zebrafish model (Danio rerio).

Cheng Y(1), Ekker M(1), Chan HM(2).

Author information:
(1)Center for Advanced Research in Environmental Genomics, University of 
Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5.
(2)Center for Advanced Research in Environmental Genomics, University of 
Ottawa, 30 Marie Curie, Ottawa, ON, Canada K1N 6N5. Electronic address: 
laurie.chan@uottawa.ca.

Pentachloroanisole (PCA) and pentachlorophenol (PCP) are chlorinated aromatic 
compounds that have been found in the environment and in human populations. The 
objective of this study is to characterize the effects of PCA in comparison to 
those of PCP on development at environmental relevant levels using a fish model. 
Zebrafish embryos were exposed to 0.1, 1, 10, 100, 500, 1000 μg/L PCA and PCP 
respectively for 96 h. Malformation observation, LC50 testing for survival rate 
at 96 hours post fertilization (hpf) and EC50 testing for hatching rate at 72 
hpf indicated that the developmental toxicity of PCP was about 15 times higher 
than that of PCA. PCP exposure at 10 μg/L resulted in elevated 3, 3', 
5-triiodothyronine (T3) levels and decreased thyroxine (T4) levels, whereas PCA 
had no effects on T3 or T4 levels. PCP and PCA exposure at 1 and 10 μg/L showed 
possible hyperthyroid effects similar to that of T3, due to increased relative 
mRNA expression of synapsin I (SYN), iodothyronine deiodinase type III (Dio3), 
thyroid hormone receptor alpha a (THRαa) and thyroid hormone receptor beta 
(THRβ), and decreased expression of iodothyronine deiodinase type II (Dio2). The 
results indicate that both PCA and PCP exposure can cause morphological 
deformities, possibly affect the timing and coordination of development in the 
central nervous system, and alter thyroid hormone levels by disrupting thyroid 
hormone regulating pathways. However, the developmental toxicity of PCA is at 
least ten times lower than that of PCP. Our results on the relative 
developmental toxicities of PCA and PCP and the possible underlying mechanisms 
will be useful to support interpretation of envrionmental concentrations and 
body burden levels observed in human populations.

Copyright © 2014 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.ecoenv.2014.10.004
PMID: 25463847 [Indexed for MEDLINE]


5. Anesthesiology. 2014 Nov;121(5):990-8. doi: 10.1097/ALN.0000000000000436.

Effects of sevoflurane and propofol on frontal electroencephalogram power and 
coherence.

Akeju O(1), Westover MB, Pavone KJ, Sampson AL, Hartnack KE, Brown EN, Purdon 
PL.

Author information:
(1)From the Department of Anesthesia, Critical Care, and Pain Medicine, 
Massachusetts General Hospital, Boston, Massachusetts (O.A., K.J.P., A.L.S., 
K.E.H., E.N.B., P.L.P.); Department of Neurology, Massachusetts General 
Hospital, Boston, Massachusetts (M.B.W.); Harvard Medical School, Boston, 
Massachusetts (O.A., E.N.B., P.L.P.); Department of Brain and Cognitive Science, 
Massachusetts Institute of Technology, Cambridge, Massachusetts (M.B.W., E.N.B., 
P.L.P.); Harvard-Massachusetts Institute of Technology Division of Health 
Sciences and Technology, Massachusetts Institute of Technology, Cambridge, 
Massachusetts (E.N.B.); and Institute for Medical Engineering and Sciences, 
Massachusetts Institute of Technology, Cambridge, Massachusetts (E.N.B.).

BACKGROUND: The neural mechanisms of anesthetic vapors have not been studied in 
depth. However, modeling and experimental studies on the intravenous anesthetic 
propofol indicate that potentiation of γ-aminobutyric acid receptors leads to a 
state of thalamocortical synchrony, observed as coherent frontal alpha 
oscillations, associated with unconsciousness. Sevoflurane, an ether derivative, 
also potentiates γ-aminobutyric acid receptors. However, in humans, 
sevoflurane-induced coherent frontal alpha oscillations have not been well 
detailed.
METHODS: To study the electroencephalogram dynamics induced by sevoflurane, the 
authors identified age- and sex-matched patients in which sevoflurane (n = 30) 
or propofol (n = 30) was used as the sole agent for maintenance of general 
anesthesia during routine surgery. The authors compared the electroencephalogram 
signatures of sevoflurane with that of propofol using time-varying spectral and 
coherence methods.
RESULTS: Sevoflurane general anesthesia is characterized by alpha oscillations 
with maximum power and coherence at approximately 10 Hz, (mean ± SD; peak power, 
4.3 ± 3.5 dB; peak coherence, 0.73 ± 0.1). These alpha oscillations are similar 
to those observed during propofol general anesthesia, which also has maximum 
power and coherence at approximately 10 Hz (peak power, 2.1 ± 4.3 dB; peak 
coherence, 0.71 ± 0.1). However, sevoflurane also exhibited a distinct theta 
coherence signature (peak frequency, 4.9 ± 0.6 Hz; peak coherence, 0.58 ± 0.1). 
Slow oscillations were observed in both cases, with no significant difference in 
power or coherence.
CONCLUSIONS: The study results indicate that sevoflurane, like propofol, induces 
coherent frontal alpha oscillations and slow oscillations in humans to sustain 
the anesthesia-induced unconscious state. These results suggest a shared 
molecular and systems-level mechanism for the unconscious state induced by these 
drugs.

DOI: 10.1097/ALN.0000000000000436
PMCID: PMC4206606
PMID: 25233374 [Indexed for MEDLINE]

Conflict of interest statement: All other authors declare no competing 
interests.