Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Fitoterapia. 2024 Oct 28;179:106278. doi: 10.1016/j.fitote.2024.106278. Online
 ahead of print.

Rare crocins ameliorate thrombus in zebrafish larvae by regulating lipid 
accumulation and clotting factors.

Xu G(1), Xu P(1), Wang N(1), Qi W(1), Pu Y(2), Kang N(3), Chu J(4), He B(5).

Author information:
(1)College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech 
University, Nanjing 211816, China.
(2)2011college, Nanjing Tech University, Nanjing 211816, China.
(3)School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, 
China.
(4)School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, 
China. Electronic address: cjl2fl@njtech.edu.cn.
(5)College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech 
University, Nanjing 211816, China; School of Pharmaceutical Sciences, Nanjing 
Tech University, Nanjing 211816, China. Electronic address: 
bingfanghe@njtech.edu.cn.

Crocin-4 is a water-soluble carotenoid that exhibits cardiovascular protection 
effects through anti-inflammatory and antioxidant effects. However, the 
pharmacodynamic effects and mechanisms of its analogues crocin-1 and crocin-2' 
have not been reported. In this study, we evaluated the protective effects of 
rare crocins on cardiovascular systems. In ox-LDL induced HUVECs model, 0.02, 
0.1, 0.5, 1, 2, 3, 4, 5, 6 μg/mL crocin-1 and crocin-2' can increase cell 
viability by up to 80 %. Meanwhile, rare crocins at concentrations between 
25-100 μg/mL crocin-1 and crocin-2' reduced the lipid accumulation by 30 % in 
cholesterol-induced zebrafish larvae. What's more, the therapeutic potential of 
rare crocins on thrombosis has also been explored. In vitro experiments, rare 
crocin-1 and crocin-2' at concentrations of 0.02, 0.05, 0.2, 0.5, 1, 2, 5, 
10 μg/mL protected Human Umbilical Vein Endothelial Cells (HUVECs) against 
lipopolysaccharides-induced oxidative stress and inflammation. In vivo studies 
revealed that rare crocins at concentrations of 25, 50, 100, 150, 200, and 
300 μg/mL exerted significant antithrombotic effect on arachidonic acid 
(AA)-induced zebrafish and there was nearly no potential risk for the deformity 
of zebrafish at 300 μg/mL dosages. In brief, rare crocins was viewed as a 
potentially useful candidate for the treatment of cardiovascular diseases 
because of its anti-inflammatory, antioxidant, and anticoagulant properties.

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

DOI: 10.1016/j.fitote.2024.106278
PMID: 39471880

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.


2. Metabolites. 2024 Oct 21;14(10):566. doi: 10.3390/metabo14100566.

Metabolomics Approach to Identify Biomarkers of Acute and Subacute Mastitis in 
Milk Samples: A Pilot Case-Control Study.

Quifer-Rada P(1)(2)(3), Aguilar-Camprubí L(1), Samino S(3)(4), Amigó N(3)(4)(5), 
Soler O(4), Padró-Arocas A(1).

Author information:
(1)LactApp Women Health, 08014 Barcelona, Spain.
(2)Department of Endocrinology & Nutrition, Biomedical Research Institute Sant 
Pau, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain.
(3)CIBER of Diabetes and Associated Metabolic Diseases, 28029 Madrid, Spain.
(4)Biosfer Teslab, 43206 Reus, Spain.
(5)Department of Basic Medical Sciences, University Rovira I Virgili, IISPV, 
43204 Reus, Spain.

Background and aims: Mastitis is one of the main complications during 
breastfeeding and contributes to the cessation of breastfeeding. However, the 
etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. 
We aimed to identify metabolic and lipidic changes in human milk during acute 
and subacute mastitis in order to detect potential biomarkers of mastitis. 
Methods: We conducted a pilot case-control study including 14 breastfeeding 
women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without 
any mastitis symptoms (control). Milk samples were collected and analyzed by 
proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess 
the association between the significant metabolites and lipids and the 
development of acute and subacute mastitis, multi-adjusted logistic regression 
models were developed. Results: The NMR-based metabolomics approach was able to 
identify and quantify a total of 40 metabolites in breast milk samples. After 
adjusting for confounding variables, acute mastitis was significantly associated 
with acetate (OR 3.9 IC 1.4-10.8), total cholesterol (OR 14 CI 3.2-62), 
esterified cholesterol (OR 3.3 CI 1.9-5.8), and sphingomyelin (OR 2.6 CI 
1.2-5.8). The other metabolites presented weak association (OR < 2.5). Subacute 
mastitis was significantly associated with glutamine, lysophosphatidylcholine, 
phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but 
only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 
1.1-6.6). Conclusions: Metabolic alteration in breast milk occurs during a 
process of both acute and subacute mastitis. Acetate, esterified cholesterol, 
lysophostidylcholine, and polyunsaturated fatty acids increased in both acute 
and subacute mastitis. However, according to the multi-adjusted regression 
logistic models, the candidate biomarkers for acute and subacute mastitis are 
cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and 
polyunsaturated fatty acids.

DOI: 10.3390/metabo14100566
PMCID: PMC11509265
PMID: 39452946

Conflict of interest statement: Paola Quifer-Rada, Laia Aguilar-Camprubí and 
Alba Padró-Arocas are employees of LactApp Women’s Health; Sara Samino, Nuria 
Amigó and Oria Soler are employees of Biosfer Teslab, The paper reflects the 
views of the scientists, and not the company.


3. EuroIntervention. 2024 Oct 21;20(20):e1276-e1287. doi: 10.4244/EIJ-D-24-00240.

Outcomes with revascularisation versus conservative management of participants 
with 3-vessel coronary artery disease in the ISCHEMIA trial.

Bangalore S(1), Rhodes G(2), Maron DJ(3), Anthopolos R(1), O'Brien SM(2), Jones 
PG(4), Mark DB(2), Reynolds HR(1), Spertus JA(4), Stone GW(5), White HD(6), Xu 
Y(1), Fremes SE(7), Hochman JS(1), Ischemia Research Group OBOT.

Author information:
(1)Department of Medicine, New York University Grossman School of Medicine, New 
York, NY, USA.
(2)Duke Clinical Research Institute, Durham, NC, USA.
(3)Department of Medicine, Stanford University, Stanford, CA, USA.
(4)Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, 
Kansas City, MO, USA.
(5)The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of 
Medicine at Mount Sinai, New York, NY, USA.
(6)Te Whatu Ora Health New Zealand, Te Toka Tumai, Green Lane Cardiovascular 
Services and University of Auckland, Auckland, New Zealand.
(7)University of Toronto, Sunnybrook Health Sciences Centre, Toronto, ON, 
Canada.

BACKGROUND: Whether revascularisation (REV) improves outcomes in patients with 
three-vessel coronary artery disease (3V-CAD) is uncertain.
AIMS: Our objective was to evaluate outcomes with REV (percutaneous coronary 
intervention [PCI] or coronary artery bypass graft surgery [CABG]) versus 
medical therapy in patients with 3V-CAD.
METHODS: ISCHEMIA participants with 3V-CAD on coronary computed tomography 
angiography without prior CABG were included. Outcomes following initial 
invasive management (INV) with REV (PCI or CABG) versus initial conservative 
management (CON) with medical therapy alone were evaluated. Regression modelling 
was used to estimate the outcomes if all participants were to undergo prompt REV 
versus those assigned to CON. Outcomes were cardiovascular (CV) death/myocardial 
infarction (MI), death, CV death, and quality of life. Bayesian posterior 
probability for benefit (Pr [benefit]) for 1 percentage point lower 4-year rates 
with REV versus CON were evaluated.
RESULTS: Among 1,236 participants with 3V-CAD (612 INV/624 CON), REV was 
associated with lower 4-year CV death/MI (adjusted 4-year difference: -4.4, 95% 
credible interval [CrI] -8.7 to -0.3 percentage points, Pr [benefit]=94.8%) when 
compared with CON, with similar results for PCI versus CON (-5.8, 95% CrI: -10.8 
to -0.5 percentage points, Pr [benefit]=96.4%) and CABG versus CON (-3.7, 95% 
CrI: -8.8 to 1.5 percentage points, Pr [benefit]=84.7%). Adjusted 4-year REV 
versus CON differences were as follows: death -1.2 (95% CrI: -4.7 to 2.2) 
percentage points, CV death -2.3 (95% CrI: -5.5 to 0.8) percentage points, with 
similar results for PCI and for CABG. The Pr (benefit) for death with REV (PCI 
or CABG) versus CON was 49-63%. The adjusted 12-month Seattle Angina 
Questionnaire-7 summary score differences favoured REV: REV versus CON 4.6 (95% 
CrI: 2.7-6.4) percentage points; PCI versus CON 3.6 (95% CrI: 1.2-5.8) 
percentage points and CABG versus CON 4.3 (95% CrI: 1.5-6.9) percentage points 
with high Pr (benefit).
CONCLUSIONS: In participants with 3V-CAD, REV (either PCI or CABG) was 
associated with a lower 4-year CV death/MI rate and improved quality of life, 
with similar results for PCI versus CON and CABG versus CON. The differences in 
all-cause mortality between REV and CON were small with wide confidence 
intervals. (ClinicalTrials.gov: NCT01471522).

DOI: 10.4244/EIJ-D-24-00240
PMCID: PMC11472139
PMID: 39432255 [Indexed for MEDLINE]

Conflict of interest statement: S. Bangalore reports grants from the National 
Heart, Lung, and Blood Institute during the conduct of the study; grants and 
personal fees from Abbott; personal fees from Biotronik, Pfizer, Amgen, and 
Reata outside of the submitted work. G. Rhodes reports NIH funding. D.J. Maron 
reports grants from the National Heart, Lung, and Blood Institute during the 
conduct of the study. R. Anthopolos reports grants from the National Heart, 
Lung, and Blood Institute during the conduct of the study. S.M. O’Brien reports 
grants from the National Heart, Lung, and Blood Institute during the conduct of 
the study. D.B. Mark reports grants from National Heart, Lung, and Blood 
Institute during the conduct of the study; and grants from HeartFlow and Merck, 
outside the submitted work. H.R. Reynolds reports grants from the National 
Heart, Lung, and Blood Institute during the conduct of the study; and 
non-financial support from Abbott, Siemens, and BioTelemetry, outside of the 
submitted work. J.A. Spertus reports grants from National Heart, Lung, and Blood 
Institute during the conduct of the study; personal fees from Bayer, Novartis, 
AstraZeneca, Amgen, Janssen, and United Healthcare; and grants from American 
College of Cardiology, outside the submitted work; in addition, he has a patent 
copyright to the Seattle Angina Questionnaire with royalties paid; is on the 
Board of Directors for Blue Cross Blue Shield of Kansas City; and reports equity 
in Health Outcomes Sciences. G.W. Stone has received speaker honoraria from 
Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, 
Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, 
Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, 
Cardiomech, Gore Medical, Amgen, Adona Medical, and Millennia Biopharma; and has 
equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of 
funds, SpectraWAVE, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; 
his daughter is an employee at Medtronic; for institutional disclosure, his 
employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, 
Bioventrix, Cardiovascular Systems Inc, Philips, Biosense Webster, Shockwave 
Medical, Vascular Dynamics, Pulnovo, and V-Wave. H.D. White reports grants from 
National Heart, Lung, and Blood Institute during the conduct of the study; 
reports receiving grant support paid to the institution and fees for serving on 
a steering committee for the ODYSSEY OUTCOMES trial (Evaluation of 
Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With 
Alirocumab) from Sanofi-Aventis and Regeneron Pharmaceuticals; for the 
ACCELERATE study (A Study of Evacetrapib in High-Risk Vascular Disease) from Eli 
Lilly; for the STRENGTH trial (Outcomes Study to Assess Statin Residual Risk 
Reduction With EpaNova in High CV Risk Patients With Hypertriglyceridemia) from 
Omthera Pharmaceuticals; for the HEART-FID study (Randomized Placebo-Controlled 
Trial of FCM as Treatment for Heart Failure With Iron Deficiency) from American 
Regent; for the CAMELLIA-TIMI study (A Study to Evaluate the Effect of Long-term 
Treatment With BELVIQ [Lorcaserin HC] on the Incidence of Major Adverse 
Cardiovascular Events and Conversion to Type 2 Diabetes Mellitus in Obese and 
Overweight Subjects With Cardiovascular Disease or Multiple Cardiovascular Risk 
Factors) from Eisai Inc; for the dal-GenE study (Effect of Dalcetrapib vs 
Placebo on CV Risk in a Genetically Defined Population With a Recent ACS) from 
DalCor Pharma UK Inc; for the AEGIS-II study from CSL Behring; for the SCORED 
trial (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients 
With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular 
Risk) and the SOLOIST-WHF trial (Effect of Sotagliflozin on Cardiovascular 
Events in Patients With Type2 Diabetes Post Worsening Heart Failure) from 
Sanofi-Aventis Australia Pty Ltd; and for the CLEAR Outcomes Study (Evaluation 
of Major Cardiovascular Events in Patients With, or at High Risk for, 
Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid. 
[ETC-1002] or Placebo) from Esperion Therapeutics Inc; he was on the advisory 
board for Genentech, Inc.; and received lecture fees from AstraZeneca. Y. Xu 
reports grants from the National Heart, Lung, and Blood Institute during the 
conduct of the study. J.S. Hochman is the PI for the ISCHEMIA trial for which, 
in addition to support by the National Heart, Lung, and Blood Institute grant, 
devices and medications were provided by Abbott, Medtronic, Abbott Laboratories 
(formerly St. Jude Medical, Inc.), Royal Philips NV (formerly Volcano 
Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck 
Sharp & Dohme Corp., Omron Healthcare, Inc., Sunovion Pharmaceuticals, Inc., 
Espero BioPharma, and Amgen, Inc.; and received financial donations from Arbor 
Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. The other authors have 
no conflicts of interest to declare.


4. Carbohydr Res. 2024 Oct 16;545:109292. doi: 10.1016/j.carres.2024.109292.
Online  ahead of print.

Picoplatin (II)-loaded chitosan nanocomposites as effective drug delivery 
systems: Preparation, mechanistic investigation of BSA/5-GMP/GSH binding and 
biological evaluations.

Ahmed NM(1), Ibrahim MM(2), Elmehasseb IM(1), Shaban SY(3).

Author information:
(1)Chemistry Department, Faculty of Science, Kafrelsheikh University, 
Kafrelsheikh 33516, Egypt.
(2)Department of Chemistry, College of Science, Taif University, P.O. Box 11099, 
Taif, 21944, Saudi Arabia.
(3)Chemistry Department, Faculty of Science, Kafrelsheikh University, 
Kafrelsheikh 33516, Egypt. Electronic address: shaban.shaban@sci.kfs.edu.eg.

The goal of the current study is to improve the characteristics and 
bioavailability of the drug picoplatin (PPt) by encapsulating it in chitosan 
nanoparticles (CS NPs) which allows for the targeted delivery of cytotoxic cargo 
to cancerous tissue, reducing toxic side effects and raising the therapeutic 
index. When picoplatin was delivered into the CS, it was able to produce a 
complex with CS (PPt@CS NPs) that had an appropriate particle size of 
275 ± 10 nm, a reasonably low PDI of 0.15 ± 0.05, and high stability 
(ζ = -22.1 ± 0.3 mV). Since almost all pharmaceuticals work by binding to 
specific proteins or DNA, the in vitro binding mechanism and affinity of bovine 
serum albumin (BSA), low molecular building units of nucleic acids (5-GMP), and 
Glutathione (GSH) (considering that cisplatin resistance could be due to a 
reaction between cisplatin and GSH) to PPt and PPt@CS NPs were examined using 
stopped-flow and other spectroscopic approaches. Through two reversible 
processes, a rapid second-order binding followed by a slower first-order 
isomerization reaction, and a static quenching mechanism, PPt and PPt@CS NPs 
bind to BSA with relative reactivity of around (PPt)/(PPt@CS NPs) = 1/2.5. The 
5-GMP interaction studies demonstrated that, in addition to changing the binding 
mechanism, PPt's encapsulation in CS increases its rate of reaction through 
coordination affinity. PPt interacted with 5-GMP via two reversible processes, a 
rapid second-order binding to phosphate followed by a slower first-order 
migration to the N7 of pyrimidine moiety. PPt@CS NPs showed weaker binding to 
GSH compared to PPt and hence PPt@CS NPs exhibits a lower resistance factor. It 
was also found that the in vitro drug release of PPt@CS NPs in PBS at pH 7.4 was 
steady, releasing 30 % of the PPt in just 5 h. Nonetheless, 75 % of the release 
in a pH 5.4 solution containing 10 mM GSH-a solution that mimics the tumor 
microenvironment-shows that the PPt@CS NPs system is sensitive to GSH and 
specifically targets malignant tissue. The encapsulation of PPt in CS complex 
maintained its anticancer activity, as shown by an in vitro cell-survival assay 
on HepG2 cancer cell lines and also cleavage efficiency toward the minor groove 
of pBR322 DNA via the hydrolytic way. These findings collectively suggested that 
inclusion PPt in CS would be an effective strategy to formulate a novel 
picoplatin formulation intended for use as targeted anticancer treatment.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.carres.2024.109292
PMID: 39427432

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. J Nutr. 2024 Oct 12:S0022-3166(24)01100-3. doi: 10.1016/j.tjnut.2024.10.023. 
Online ahead of print.

A Method to Estimate the Dietary α-Linolenic Acid Requirement Using 
Nonesterified DHA and Arachidonic Acid Oxylipins and Fatty Acids.

Manson A(1), Sidhu KK(1), Fedorova O(1), La HHK(1), Magaji E(1), Nguyen LKL(1), 
Winter T(1), Aukema HM(2).

Author information:
(1)Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, 
Canada; Canadian Centre for Agri-Food Research in Health and Medicine (CCARM), 
Winnipeg, MB, Canada.
(2)Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, 
Canada; Canadian Centre for Agri-Food Research in Health and Medicine (CCARM), 
Winnipeg, MB, Canada. Electronic address: harold.aukema@umanitoba.ca.

BACKGROUND: The dietary requirement for α-linolenic acid (ALA) remains unclear, 
as evidenced by the absence of an RDA for this essential fatty acid (FA). In 
previous studies, we observed that the amount of dietary ALA required to 
maximize nonesterified (NE) DHA oxylipins appears to be higher than the amount 
required to maximize tissue esterified DHA levels, which have classically been 
used to estimate the ALA requirement. Further, we observed that dietary ALA 
reduces esterified arachidonic acid (ARA) and its NE oxylipins.
OBJECTIVES: Since NE oxylipins and FA mediate the biological activities of FA, 
we examined whether these DHA and ARA pools could be used to determine the 
dietary ALA requirement.
METHODS: Nine groups of 4-wk-old male Sprague-Dawley rats (n = 5) and 10 groups 
of male and female CD1 mice (n = 6) were provided 0.1-2.5 g ALA and 2 g of 
linoleic acid per 100 g of AIN93G-based diets. NE DHA and ARA and their 
oxylipins in serum, liver, kidney, and brain homogenates underwent solid phase 
extraction and were quantified by HPLC-MS/MS. Breakpoint analysis of transitions 
from increase to plateau was conducted using piecewise regression.
RESULTS: In response to increasing dietary ALA, NE DHA oxylipins, and DHA in 
serum, liver, and kidney (but not the brain) initially increased rapidly and 
then plateaued whereas ARA oxylipins and ARA tended to decrease and plateau. 
Thus, breakpoints were calculated for the ratios of DHA/ARA and 
hydroxy-DHA/hydroxy-ARA (DHAOH/ARAOH), which consisted of oxylipins synthesized 
via pathways common to both FA. In serum, liver, and kidney, the highest 
estimated breakpoint indicated an ALA requirement of ∼0.7 g/100 g diet (1.7% 
energy), approximately twice that of previous estimations.
CONCLUSIONS: This study supports the use of NE DHAOH/ARAOH or DHA/ARA as 
biochemical indicators of the ALA requirement. Applying this method in rats and 
mice indicates that the requirement is higher than previously estimated using 
esterified DHA alone.

Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All 
rights reserved.

DOI: 10.1016/j.tjnut.2024.10.023
PMID: 39401685

Conflict of interest statement: Conflict of interest statement The authors 
report no conflict of interest.