Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Nutr Rev. 2024 Sep 27:nuae133. doi: 10.1093/nutrit/nuae133. Online ahead of 
print.

Exhaustive Search of Dietary Intake Biomarkers as Objective Tools for 
Personalized Nutrimetabolomics and Precision Nutrition Implementation.

de la O V(1)(2), Fernández-Cruz E(1)(2), Valdés A(3), Cifuentes A(3), Walton 
J(4), Martínez JA(1)(5)(6).

Author information:
(1)Nutrition Precision and Cardiometabolic Health Program of IMDEA-Food 
Institute (Madrid Institute for Advances Studies), 28040, Madrid, Spain.
(2)Faculty of Health Sciences, International University of La Rioja, 26006, 
Logroño, Spain.
(3)Foodomics Lab, Institute of Food Science Research, Spanish National Research 
Council, 28049, Madrid, Spain.
(4)Department of Biological Sciences, Munster Technological University, Cork, 
Republic of Ireland.
(5)Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la 
Nutrición, Instituto de Salud Carlos III, 28049, Madrid, Spain.
(6)Department of Medicine and Endocrinology, Campus of Soria, University of 
Valladolid, Valladolid, Spain.

OBJECTIVE: To conduct an exhaustive scoping search of existing literature, 
incorporating diverse bibliographic sources to elucidate the relationships 
between metabolite biomarkers in human fluids and dietary intake.
BACKGROUND: The search for biomarkers linked to specific dietary food intake 
holds immense significance for precision health and nutrition research. Using 
objective methods to track food consumption through metabolites offers a more 
accurate way to provide dietary advice and prescriptions on healthy dietary 
patterns by healthcare professionals. An extensive investigation was conducted 
on biomarkers associated with the consumption of several food groups and 
consumption patterns. Evidence is integrated from observational studies, 
systematic reviews, and meta-analyses to achieve precision nutrition and 
metabolism personalization.
METHODS: Tailored search strategies were applied across databases and gray 
literature, yielding 158 primary research articles that met strict inclusion 
criteria. The collected data underwent rigorous analysis using STATA and Python 
tools. Biomarker-food associations were categorized into 5 groups: cereals and 
grains, dairy products, protein-rich foods, plant-based foods, and a 
miscellaneous group. Specific cutoff points (≥3 or ≥4 bibliographic appearances) 
were established to identify reliable biomarkers indicative of dietary 
consumption.
RESULTS: Key metabolites in plasma, serum, and urine revealed intake from 
different food groups. For cereals and grains, 3-(3,5-dihydroxyphenyl) propanoic 
acid glucuronide and 3,5-dihydroxybenzoic acid were significant. Omega-3 fatty 
acids and specific amino acids showcased dairy and protein foods consumption. 
Nuts and seafood were linked to hypaphorine and trimethylamine N-oxide. The 
miscellaneous group featured compounds like theobromine, 7-methylxanthine, 
caffeine, quinic acid, paraxanthine, and theophylline associated with coffee 
intake.
CONCLUSIONS: Data collected from this research demonstrate potential for 
incorporating precision nutrition into clinical settings and nutritional advice 
based on accurate estimation of food intake. By customizing dietary 
recommendations based on individualized metabolic profiles, this approach could 
significantly improve personalized food consumption health prescriptions and 
support integrating multiple nutritional data.This article is part of a 
Nutrition Reviews special collection on Precision Nutrition.

© The Author(s) 2024. Published by Oxford University Press on behalf of the 
International Life Sciences Institute. All rights reserved. For permissions, 
please e-mail: journals.permissions@oup.com.

DOI: 10.1093/nutrit/nuae133
PMID: 39331531


2. J Transl Med. 2024 May 31;22(1):525. doi: 10.1186/s12967-024-05312-6.

Bifidobacterium adolescentis-derived hypaphorine alleviates acetaminophen 
hepatotoxicity by promoting hepatic Cry1 expression.

Qin P(#)(1)(2), Li Y(#)(3)(4), Su Y(#)(1), Wang Z(#)(5), Wu R(2), Liang X(6), 
Zeng Y(1), Guo P(2), Yu Z(2), Huang X(2), Yang H(5), Zeng Z(3), Zhao X(2), Gong 
S(2), Han J(7), Chen Z(8), Xiao W(9), Chen A(10).

Author information:
(1)Center for Drug Research and Development, Guangdong Provincial Key Laboratory 
of Advanced Drug Delivery System, Guangdong Pharmaceutical University, 
Guangzhou, 510006, China.
(2)School of Traditional Chinese Medicine, Southern Medical University, 
Guangzhou, 510515, China.
(3)Department of Critical Care Medicine, Nanfang Hospital, Southern Medical 
University, Guangzhou, 510515, China.
(4)School of Nursing, Southern Medical University, Guangzhou, 510515, China.
(5)Department of Critical Care Medicine, The Third Affiliated Hospital of 
Southern Medical University, Guangzhou, 510665, China.
(6)The First School of Clinical Medicine, Southern Medical University, 
Guangzhou, 510515, China.
(7)Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 
Guangzhou, 510623, China. jchan123@126.com.
(8)Department of Critical Care Medicine, Nanfang Hospital, Southern Medical 
University, Guangzhou, 510515, China. zhongqingchen2008@163.com.
(9)Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, 
Guangdong Pharmaceutical University, Guangzhou, 510006, China. 
xw7688@smu.edu.cn.
(10)Center for Drug Research and Development, Guangdong Provincial Key 
Laboratory of Advanced Drug Delivery System, Guangdong Pharmaceutical 
University, Guangzhou, 510006, China. chenali2004@163.com.
(#)Contributed equally

Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health 
concern. Although evidence suggests that Bifidobacterium adolescentis (B. 
adolescentis) can be used to treat liver disease, it is unclear if it can 
prevent AILI. In this report, we prove that B. adolescentis significantly 
attenuated AILI in mice, as demonstrated through biochemical analysis, 
histopathology, and enzyme-linked immunosorbent assays. Based on untargeted 
metabolomics and in vitro cultures, we found that B. adolescentis generates 
microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the 
inflammatory response and hepatic oxidative stress to alleviate AILI in mice. 
Transcriptomic analysis indicates that Cry1 expression is increased in 
APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its 
stabilizer KL001 effectively mitigates liver damage arising from oxidative 
stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, 
we verified that Cry1 gene expression was also decreased in patients with 
APAP-induced acute liver failure. In conclusion, this study demonstrates that B. 
adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which 
subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

© 2024. The Author(s).

DOI: 10.1186/s12967-024-05312-6
PMCID: PMC11143572
PMID: 38822329 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no competing 
interests.


3. Food Sci Nutr. 2023 Aug 17;11(11):7026-7038. doi: 10.1002/fsn3.3626.
eCollection  2023 Nov.

Hepatoprotective effects of Niudali (Callerya speciosa) root aqueous extracts 
against tetrachloromethane-induced acute liver injury and inflammation.

Zhang Y(1), Huang J(1), Gan L(1)(2), Wu R(1)(2), Jin J(1)(2), Wang T(3), Sun 
S(4), Zhang Z(4), Li L(5), Zheng X(1), Zhang K(1), Sun L(4), Ma H(1)(2)(3), Li 
D(1)(2).

Author information:
(1)School of Biotechnology and Health Sciences Wuyi University Jiangmen China.
(2)International Healthcare Innovation Institute (Jiangmen) Jiangmen China.
(3)Bioactive Botanical Research Laboratory, Biomedical and Pharmaceutical 
Sciences, College of Pharmacy University of Rhode Island Kingston Rhode Island 
USA.
(4)Tea Research Institute, Guangdong Academy of Agricultural Sciences/Guangdong 
Key Laboratory of Tea Resources Innovation & Utilization Guangzhou China.
(5)Institute of Microbial Pharmaceuticals, College of Life and Health Sciences 
Northeastern University Shenyang China.

Niudali (Callerya speciosa) is commonly grown in southeastern regions of China 
and consumed as a food ingredient. Although Niudali root extracts showed various 
biological activities, the hepatoprotective effects of Niudali root 
phytochemicals are not fully studied. Herein, we prepared two Niudali root 
aqueous extracts, namely, c and Niudali polysaccharides-enriched extract (NPE), 
and identified an alkaloid, (hypaphorine) in NEW. The hepatoprotective effects 
of NWE, NPE, and hypaphorine were evaluated in an acute liver injury model 
induced by carbon tetrachloride (CCl4) in mice. Pathohistological examination 
and blood chemistry assays showed that treatment of NWE, NPE, and hypaphorine 
alleviated CCl4-induced liver damage by lowering the liver injury score (by 
75.51%, 80.01%, and 41.22%) and serum aspartate and alanine transaminases level 
(by 63.24%, 85.22%, and 49.74% and by 78.73%, 80.08%, and 81.70%), respectively. 
NWE, NPE, and hypaphorine also reduced CCl4-induced hepatic oxidative stresses 
in the liver tissue by decreasing the levels of malondialdehyde (by 40.00%, 
51.25%, and 28.75%) and reactive oxygen species (by 30.22%, 36.14%, and 33.54%) 
while increasing the levels of antioxidant enzymes including superoxide 
dismutase (by 21.36%, 21.64%, and 8.90%), catalase (by 22.13%, 33.33%, and 
5.39%), and glutathione (by 84.87%, 90.65%, and 80.53%), respectively. 
Mechanistic assays showed that NWE, NPE, and hypaphorine alleviated liver damage 
by mediating inflammatory biomarkers (e.g., pro-inflammatory cytokines) via the 
signaling pathways of mitogen-activated protein kinases and nuclear factor-κB. 
Findings from our study extend the understanding of Niudali's hepatoprotective 
effects, which is useful for its development as a dietary intervention for liver 
inflammation.

© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.

DOI: 10.1002/fsn3.3626
PMCID: PMC10630805
PMID: 37970412

Conflict of interest statement: The authors declare that they have no competing 
interests.


4. Atherosclerosis. 2023 Oct;382:117285. doi: 
10.1016/j.atherosclerosis.2023.117285. Epub 2023 Sep 9.

Plasma metabolomic profiles of plant-based dietary indices reveal potential 
pathways for metabolic syndrome associations.

Lanuza F(1), Meroño T(2), Zamora-Ros R(3), Bondonno NP(4), Rostgaard-Hansen 
AL(5), Sánchez-Pla A(6), Miro B(7), Carmona-Pontaque F(6), Riccardi G(8), 
Tjønneland A(5), Landberg R(9), Halkjær J(5), Andres-Lacueva C(1).

Author information:
(1)Biomarkers and Nutrimetabolomics Laboratory, Department de Nutrició, Ciències 
de L'Alimentació i Gastronomia, Institut de Recerca en Nutrició i Seguretat 
Alimentària (INSA-UB), Facultat de Farmàcia i Ciències de L'Alimentació, 
Universitat de Barcelona (UB), 08028, Barcelona, Spain; Centro de Investigación 
Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto 
de Salud Carlos III, Madrid, 28029, Spain.
(2)Biomarkers and Nutrimetabolomics Laboratory, Department de Nutrició, Ciències 
de L'Alimentació i Gastronomia, Institut de Recerca en Nutrició i Seguretat 
Alimentària (INSA-UB), Facultat de Farmàcia i Ciències de L'Alimentació, 
Universitat de Barcelona (UB), 08028, Barcelona, Spain; Centro de Investigación 
Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto 
de Salud Carlos III, Madrid, 28029, Spain. Electronic address: 
tomasmerono@ub.edu.
(3)Biomarkers and Nutrimetabolomics Laboratory, Department de Nutrició, Ciències 
de L'Alimentació i Gastronomia, Institut de Recerca en Nutrició i Seguretat 
Alimentària (INSA-UB), Facultat de Farmàcia i Ciències de L'Alimentació, 
Universitat de Barcelona (UB), 08028, Barcelona, Spain; Unit of Nutrition and 
Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology 
(ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. 
Electronic address: rzamora@idibell.cat.
(4)Danish Cancer Society Research Center, Strandboulevarden 49, DK 2100, 
Copenhagen, Denmark; Nutrition and Health Innovation Research Institute, School 
of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
(5)Danish Cancer Society Research Center, Strandboulevarden 49, DK 2100, 
Copenhagen, Denmark.
(6)Statistics and Bioinformatics Research Group, Department of Genetics, 
Microbiology and Statistics, University of Barcelona, Barcelona, Spain.
(7)Biomarkers and Nutrimetabolomics Laboratory, Department de Nutrició, Ciències 
de L'Alimentació i Gastronomia, Institut de Recerca en Nutrició i Seguretat 
Alimentària (INSA-UB), Facultat de Farmàcia i Ciències de L'Alimentació, 
Universitat de Barcelona (UB), 08028, Barcelona, Spain; Statistics and 
Bioinformatics Research Group, Department of Genetics, Microbiology and 
Statistics, University of Barcelona, Barcelona, Spain.
(8)Department of Clinical Medicine and Surgery, University of Naples Federico 
II, Naples, Italy.
(9)Department of Biology and Biological Engineering, Division of Food and 
Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden.

BACKGROUND AND AIMS: Plant-based dietary patterns have been associated with 
improved health outcomes. This study aims to describe the metabolomic 
fingerprints of plant-based diet indices (PDI) and examine their association 
with metabolic syndrome (MetS) and its components in a Danish population.
METHODS: The MAX study comprised 676 participants (55% women, aged 18-67 y) from 
Copenhagen. Sociodemographic and dietary data were collected using 
questionnaires and three 24-h dietary recalls over one year (at baseline, and at 
6 and 12 months). Mean dietary intakes were computed, as well as overall PDI, 
healthful (hPDI) and unhealthful (uPDI) scores, according to food groups for 
each plant-based index. Clinical variables were also collected at the same time 
points in a health examination that included complete blood tests. MetS was 
defined according to the International Diabetes Federation criteria. Plasma 
metabolites were measured using a targeted metabolomics approach. Metabolites 
associated with PDI were selected using random forest models and their 
relationships with PDIs and MetS were analyzed using generalized linear mixed 
models.
RESULTS: The mean prevalence of MetS was 10.8%. High, compared to low, hPDI and 
uPDI scores were associated with a lower and higher odd of MetS, respectively 
[odds ratio (95%CI); hPDI: 0.56 (0.43-0.74); uPDI: 1.61 (1.26-2.05)]. Out of 411 
quantified plasma metabolites, machine-learning metabolomics fingerprinting 
revealed 13 metabolites, including food and food-related microbial metabolites, 
like hypaphorine, indolepropionic acid and lignan-derived enterolactones. These 
metabolites were associated with all PDIs and were inversely correlated with 
MetS components (p < 0.05). Furthermore, they had an explainable contribution of 
12% and 14% for the association between hPDI or uPDI, respectively, and MetS 
only among participants with overweight/obesity.
CONCLUSIONS: Metabolites associated with PDIs were inversely associated with 
MetS and its components, and may partially explain the effects of plant-based 
diets on cardiometabolic risk factors.

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

DOI: 10.1016/j.atherosclerosis.2023.117285
PMID: 37778133 [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. J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117120. doi:
10.1016/j.jep.2023.117120.  Epub 2023 Sep 2.

Discovery and verification of Q-markers for promoting blood circulation and 
removing stasis of raw and wine-steamed Vaccaria segetalis based on 
pharmacological evaluation combined with chemometrics.

Bing Y(1), Sun Z(2), Wu S(3), Zheng Y(4), Xi Y(5), Li W(6), Zou X(7), Qu Z(8).

Author information:
(1)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China. 
Electronic address: 1941051633@qq.com.
(2)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China. 
Electronic address: sunzhiwei@hrbcu.edu.cn.
(3)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China. 
Electronic address: 460735845@qq.com.
(4)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China. 
Electronic address: 2841955229@qq.com.
(5)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China. 
Electronic address: 1822476115@qq.com.
(6)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China; 
Engineering Research Center on Natural Antineoplastic Drugs, Ministry of 
Education, Harbin University of Commerce, Harbin, 150076, China. Electronic 
address: lwldzd@163.com.
(7)Engineering Research Center on Natural Antineoplastic Drugs, Ministry of 
Education, Harbin University of Commerce, Harbin, 150076, China. Electronic 
address: zouxiang@hrbcu.edu.cn.
(8)School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China. 
Electronic address: qiuqiuqu@163.com.

ETHNOPHARMACOLOGICAL RELEVANCE: Dried and mature seeds of Vaccaria segetalis 
(Neck.) Garcke ex Asch. (VS) are known for their therapeutic effects, as they 
stimulate blood circulation, promote menstruation and diuresis and eliminate 
gonorrhoea. However, due to its hard shell, the dissolution of its active 
ingredients is often improved by steaming and frying in clinical applications. 
Among the processed products, wine-steamed Vaccaria segetalis (WVS) is one of 
the commonly used ones. Numerous historical records have shown that wine 
steaming can enhance the efficacy of drugs to promote blood circulation and 
remove blood stasis. However, the differences in the efficacy of VS and WVS in 
promoting blood circulation and removing blood stasis have not been thoroughly 
studied, and the possible reasons for these differences have not been reported.
AIM OF THE STUDY: The objective of this study was to identify quality markers 
(Q-markers) that could differentiate the efficacy of promoting blood circulation 
and removing blood stasis of VS and WVS, which could serve as a basis for the 
rational application of VS and WVS in clinical settings.
MATERIALS AND METHODS: A pharmacodynamic comparison between the water extracts 
of VS and WVS was carried out based on a mouse acute blood stasis model (ABS) 
and thrombus zebrafish model. The potential bioactive substances of WVS were 
screened by investigating the correlation between common peaks identified for 10 
batches of WVS by ultra-performance liquid chromatography quadrupole 
time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and their rate of thrombosis 
inhibition in zebrafish. Furthermore, multivariate statistical analysis of 
chemical components between VS and WVS was conducted to speculate the Q-markers 
combined with the results of the bioactive components. Based on the efficacy 
verification of Q-markers, the content of Q-markers in 10 batches of WVS was 
evaluated.
RESULTS: The results of efficacy comparison assays demonstrated that the 
efficacy of WVS was more prominent than VS at the same dose. Five components 
were screened as effective components of WVS for promoting blood circulation and 
removing blood stasis by correlation analysis. Furthermore, a total of 24 common 
ingredients were identified in VS and WVS extracts, and 9 of them showed 
increased dissolution rate after wine steaming, including 4 active ingredients, 
Hypaphorine, Vaccarin, Saponarin, and Isovitexin-2″-O-arabinoside, which were 
screened out by correlation analysis. The monomer test suggested that these 4 
components could activate blood circulation and remove blood stasis in a 
dose-dependent manner. Consequently, Hypaphorine, Vaccarin, Saponarin, and 
Isovitexin-2″-O-arabinoside were selected as Q-markers to distinguish between VS 
and WVS. The content determination showed that the total contents of 4 Q-markers 
of WVS from 10 batches with different origins ranged from 0.478% to 0.716%.
CONCLUSIONS: This study compared the efficacy of VS and WVS in promoting blood 
circulation and resolving stasis and revealed Q-markers that reflected the 
difference in efficacy between them for the first time, which laid the 
foundation for establishing quality standards for WVS.

Copyright © 2023 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jep.2023.117120
PMID: 37666377 [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.