Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Agric Food Chem. 2024 Nov 5. doi: 10.1021/acs.jafc.4c08663. Online ahead of 
print.

Design, Synthesis, and Biological Activity Studies of Myricetin Derivatives 
Containing a Diisopropanolamine Structure.

An Y(1), Zou H(1), Zhou Q(1), Deng T(1), Tian J(1), Qiu Y(1), Xue W(1).

Author information:
(1)State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals, 
Guizhou University, Guiyang 550025, P. R. China.

A series of myricetin derivatives containing diisopropanolamine were designed 
and synthesized. The in vitro inhibitory effects of the target compounds on 9 
fungal pathogens and 3 bacterial pathogens were also evaluated. A12 had the best 
inhibitory effect against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 
value of 4.9 μg/mL, which was better than zinc-thiazole (ZT: EC50 = 7.3 μg/mL) 
and thiodiazole-copper (TC: EC50 = 65.5 μg/mL); A25 had the best inhibitory 
effect against Phomopsis sp. (Ps), with an EC50 value of 17.2 μg/mL, which was 
better than azoxystrobin (Az: EC50 = 22.3 μg/mL). In vivo inhibition tests were 
performed on kiwifruit for A25 and rice leaves for A12. At 200 μg/mL, the 
curative activity of A12 against rice leaf blight was 40.7%, which was better 
than that of ZT (37.2%) and TC (32.9%), and the protective activity of A12 was 
44.8%, which was better than that of ZT (39.5%) and TC (34.6%). The curative 
activity of A25 against kiwi soft rot disease was 70.1%, which was better than 
that of Az (62.8%). Preliminary elucidation of the possible mechanisms of action 
was carried out by experiments on fluorescence microscopy, scanning electron 
microscopy, formation of biofilms, density functional theory calculations, and 
so on.

DOI: 10.1021/acs.jafc.4c08663
PMID: 39498550


2. Nutr Metab Insights. 2024 Oct 29;17:11786388241283779. doi: 
10.1177/11786388241283779. eCollection 2024.

Dietary Flavonoid Intake and Risk of Mild Cognitive Impairment in the Elderly: A 
Case-Control Study.

Liu Q(1), Zhang R(1), Chen Y(2), Lu Y(3), Cui F(4), Zhang Q(1), Zhang C(1).

Author information:
(1)Department of Nutrition, Beijing Luhe Hospital, Capital Medical University, 
Beijing, China.
(2)Prenatal Diagnostic Center, Beijing Obstetrics and Gynecology Hospital, 
Capital Medical University, Beijing, China.
(3)School of Nursing, Peking University Health Science Center, Beijing, China.
(4)Department of Nephrology, Beijing Hospital of Traditional Chinese Medicine, 
Capital Medical University, Beijing, China.

BACKGROUND: This study investigates the association between dietary flavonoid 
intake and the incidence of mild cognitive impairment (MCI) through a matched 
case-control design.
METHODS: Dietary intake was assessed using a food frequency questionnaire, 
comparing the intake of flavonoids between individuals with MCI and those with 
normal cognitive function. Logistic regression analysis was employed to evaluate 
the correlation between dietary flavonoid intake and the risk of MCI. 
Additionally, blood concentrations of S100β, a marker of the blood-brain barrier 
(BBB) integrity, were measured using electrochemiluminescence immunoassay, and 
Pearson correlation analysis was conducted to explore the relationship between 
dietary flavonoid intake and blood S100β levels.
RESULTS: Compared to participants with normal cognition, those with MCI had 
significantly lower dietary intakes of total flavonoids, isoflavones, daidzein, 
glycitein, genistein, kaempferol, myricetin, flavonols, and anthocyanidins, 
while the intake of peonidin was significantly higher. Univariate logistic 
regression analysis indicated that high dietary intake of total flavonoids, 
isoflavones, daidzein, glycitein, genistein, kaempferol, myricetin, and 
flavonols was negatively correlated with MCI, whereas peonidin intake was 
positively correlated with MCI. Multivariate logistic regression analysis 
confirmed these findings. Pearson correlation analysis revealed a significant 
negative correlation between dietary intake of kaempferol and myricetin and 
blood S100β levels.
CONCLUSION: Increasing the dietary intake of total flavonoids, isoflavones, 
daidzein, glycitein, genistein, and flavonols appears to be a protective factor 
against MCI, while higher intake of peonidin is associated with an increased 
risk of MCI. The protective or adverse effects of these flavonoids may not be 
related to the permeability of the BBB. Myricetin and kaempferol intake may 
protect cognitive function by maintaining BBB integrity.

Plain Language Summary: Brief highlights: More attention to neurons Previous 
studies on the cognitive effects of flavonoid intake have mainly focused on 
their direct effects on central neurons and glial cells. Less attention to BBB 
damage Few studies have investigated the effects of flavonoid intake on the BBB, 
which indirectly affects cognitive function. Negative correlation between BBB 
damage and Myricetin and Kaempferol It was found that Myricetin and Kaempferol, 
two components of flavonoids, were negatively correlated with the risk of MCI 
and negatively correlated with blood levels of the BBB integrity marker S100β. 
They may protect cognitive function in middle-aged and elderly people by 
preserving the integrity of the BBB.

© The Author(s) 2024.

DOI: 10.1177/11786388241283779
PMCID: PMC11528669
PMID: 39493860

Conflict of interest statement: The author(s) declared no potential conflicts of 
interest with respect to the research, authorship, and/or publication of this 
article.


3. J Transl Med. 2024 Nov 2;22(1):992. doi: 10.1186/s12967-024-05808-1.

Flavonoids attenuate inflammation of HGF and HBMSC while modulating the 
osteogenic differentiation based on microfluidic chip.

Du S(1)(2), Wang Z(1), Zhu H(1), Tang Z(3), Li Q(4).

Author information:
(1)Second Clinical Division, Peking University School and Hospital of 
Stomatology & National Center for Stomatology & National Clinical Research 
Center for Oral Diseases & National Engineering Research Center of Oral 
Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, 
Haidian District, Beijing, 100081, People's Republic of China.
(2)Center for Digital Dentistry, Peking University School and Hospital of 
Stomatology & National Center for Stomatology & National Clinical Research 
Center for Oral Diseases & National Engineering Research Center of Oral 
Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, 
Haidian District, Beijing, 100081, People's Republic of China.
(3)Second Clinical Division, Peking University School and Hospital of 
Stomatology & National Center for Stomatology & National Clinical Research 
Center for Oral Diseases & National Engineering Research Center of Oral 
Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, 
Haidian District, Beijing, 100081, People's Republic of China. 
zhihui_tang@bjmu.edu.cn.
(4)Center for Digital Dentistry, Peking University School and Hospital of 
Stomatology & National Center for Stomatology & National Clinical Research 
Center for Oral Diseases & National Engineering Research Center of Oral 
Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, 
Haidian District, Beijing, 100081, People's Republic of China. 
qingli@bjmu.edu.cn.

BACKGROUND: When inflammation occurs in periodontal tissues, a dynamic cellular 
crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal 
stem cells (BMSCs), which plays a crucial role in the biological behaviour and 
differentiation of the cells. Recently, flavonoids are increasingly recognized 
for their therapeutic potential in modulating inflammation and osteogenic 
differentiation. Owing to their varied molecular structures and mechanisms, 
there are more needs that flavonoid compounds should be identified by extensive 
screening. However, current drug research mostly relies on static, single-type 
cell cultures. In this study, an innovative bionic microfluidic chip system 
tailored for both soft and hard tissues was developed to screen for flavonoids 
suitable for treating periodontitis.
METHODS: This study developed a microfluidic system that bionically simulates 
the soft and hard structures of periodontal tissues. Live/dead staining, 
reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. 
These techniques evaluated the effects of flavonoid compounds on the levels of 
inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. 
Additionally, the impact of these compounds on osteogenic induction in HBMSC and 
the exploration of the underlying mechanisms were assessed.
RESULTS: The microfluidic chip used in this study features dual chambers 
separated by a porous membrane, allowing cellular signal communication via 
bioactive factors secreted by cells in both layers under perfusion. The 
inflammatory response within the chip under LPS stimulation was lower compared 
to individual static cultures of HGF and HBMSC. The selected 
flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular 
inflammation, decreased ROS levels, and enhanced osteogenic differentiation of 
BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated 
favorable outcomes in reducing inflammation, lowering ROS levels, and promoting 
osteogenic differentiation through the Wnt/β-catenin pathway.
CONCLUSIONS: The bionic microfluidic chip system provides enhanced capabilities 
for drug screening and evaluation, delivering a more precise assessment of drug 
efficacy and safety compared to traditional in vitro methods. This study 
demonstrates the efficacy of flavonoids in influencing osteogenic processes in 
BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the 
potential of flavonoids as therapeutic medicine for treating periodontitis, 
meriting further research and development.

© 2024. The Author(s).

DOI: 10.1186/s12967-024-05808-1
PMCID: PMC11531701
PMID: 39488714 [Indexed for MEDLINE]

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


4. Biomed Pharmacother. 2024 Oct 31;181:117642. doi:
10.1016/j.biopha.2024.117642.  Online ahead of print.

Citrus flavonoids diosmin, myricetin and neohesperidin as inhibitors of 
Pseudomonas aeruginosa: Evidence from antibiofilm, gene expression and in vivo 
analysis.

Carević T(1), Kolarević S(1), Kolarević MK(1), Nestorović N(1), Novović K(2), 
Nikolić B(3), Ivanov M(4).

Author information:
(1)Institute for Biological Research "Siniša Stanković", National Institute of 
the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 
142, Belgrade 11108, Serbia.
(2)Institute of Molecular Genetics and Genetic Engineering, University of 
Belgrade, Vojvode Stepe 444a, Belgrade 11042, Serbia.
(3)Faculty of Biology, University of Belgrade, Studentski trg 16, Belgrade 
11000, Serbia.
(4)Institute for Biological Research "Siniša Stanković", National Institute of 
the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 
142, Belgrade 11108, Serbia. Electronic address: 
marija.smiljkovic@ibiss.bg.ac.rs.

Citrus flavonoids are group of bioactive polyphenols. Here, we investigated the 
potential of diosmin, myricetin and neohesperidin as possible inhibitors of 
Pseudomonas aeruginosa. This bacterium is a major clinical challenge due to its 
propensity to form resistant biofilm. The aims of this study were to examine 
flavonoids antibacterial activity using the microdilution method, assays 
intended to determine several antibiofilm mechanisms (crystal violet, congo red 
binding, extracellular DNA (eDNA) test and confocal laser scanning microscopy 
(CLSM) live/dead cell imaging), followed by virulence genes RT-qPCR analysis. 
Furthermore, we aimed to examine in vivo toxicity of the compounds as well as 
their efficacy in P. aeruginosa zebrafish embryo infection model. Minimal 
inhibitory concentrations of tested flavonoids towards P. aeruginosa were in 
range 0.05 - 0.4 mg/mL. A high potential of the compounds to disturb both the 
formation of the bacterial biofilm and its eradication was recorded, including 
significant reduction in biofilm biomass, exopolysaccharide and eDNA production. 
Biofilm treatment with diosmin resulted in the lowest percentage of live 
microbial cells as observed in the CLSM live/dead cell imaging. The lasI, pvdS, 
and rhlC genes were found to be downregulated in the presence of diosmin and 
myricetin. Only diosmin stood out as non-embryotoxic. Consequently, in vivo 
analysis using a zebrafish model of P. aeruginosa infection showed an 
antivirulence effect of diosmin. Our findings suggest that diosmin could be 
potential candidate for the development of new agent that target P. aeruginosa 
infections by reducing its virulence mechanisms.

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights 
reserved.

DOI: 10.1016/j.biopha.2024.117642
PMID: 39486364

Conflict of interest statement: Declaration of Competing Interest Na.


5. Life (Basel). 2024 Sep 25;14(10):1222. doi: 10.3390/life14101222.

Network Pharmacology, Molecular Dynamics and In Vitro Assessments of Indigenous 
Herbal Formulations for Alzheimer's Therapy.

Ojo OA(1)(2), Ajayi-Odoko OA(3), Gyebi GA(4)(5), Ayokunle DI(6), Ogunlakin 
AD(1)(2), Ezenabor EH(1)(2), Olanrewaju AA(7), Agbeye OD(1)(2), Ogunwale ET(8), 
Rotimi DE(9)(10), Fouad D(11), Batiha GE(12), Adeyemi OS(1)(2)(13).

Author information:
(1)Good Health and Wellbeing Research Clusters (SDG 03), Bowen University, Iwo 
232102, Nigeria.
(2)Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research 
Group, Biochemistry Programme, Bowen University, Iwo 232102, Nigeria.
(3)Microbiology Programme, Bowen University, Iwo 232102, Nigeria.
(4)Natural Products and Structural (Bio-Chem)-Informatics Research Laboratory 
(NpsBC-RI), Department of Biochemistry, Bingham University, Karu 961105, 
Nigeria.
(5)Department of Biotechnology and Food Science, Faculty of Applied Sciences, 
Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa.
(6)Pure and Applied Biology Programme, Bowen University, Iwo 232102, Nigeria.
(7)Chemistry and Industrial Chemistry Programme, Bowen University, Iwo 232102, 
Nigeria.
(8)Animal Science Programme, Bowen University, Iwo 232102, Nigeria.
(9)Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School 
of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los 
Angeles, CA 90089, USA.
(10)Department of Biochemistry, Landmark University, Omu-Aran 251101, Nigeria.
(11)Department of Zoology, College of Science, King Saud University, P.O. Box 
22452, Riyadh 11495, Saudi Arabia.
(12)Department of Pharmacology and Therapeutic, Faculty of Veterinary Medicine, 
Damanhour University, Damanhour 22511, AlBeheira, Egypt.
(13)Laboratory of Sustainable Animal Environment Systems, Graduate School of 
Agricultural Sciences, Tohoku University, Sendai 980-8579, Japan.

Alzheimer's disease (AD) is an age-associated neurodegenerative condition marked 
by amyloid plaques, synaptic dysfunction, and neuronal loss. Besides 
conventional medical care, herbal therapies, both raw and refined, have 
attracted researchers for their potential therapeutic effects. As a 
proof-of-concept, our study combined HPLC-DAD analysis of bioactive 
constituents, network pharmacology, molecular dynamics (MD), molecular docking, 
post-MD analysis, and experimental verification to investigate the mechanisms of 
crude drug formulations as a therapeutic strategy for AD. We identified nine 
bioactive compounds targeting 188 proteins and 1171 AD-associated genes. Using a 
Venn diagram, we found 47 overlapping targets, forming "herb-compound-target 
(HCT)" interaction networks and a protein‒protein interaction (PPI) network. 
Simulations analyzed binding interactions among the three core targets and their 
compounds. MD assessed the stability of the best-ranked poses and beneficial 
compounds for each protein. Among the top 22 hub genes, AChE, BChE, and MAO, 
ranked 10, 14, and 34, respectively, were selected for further analysis. Two 
tetraherbal formulations, Form A and Form B, showed notable activity against 
AChE. Form A exhibited significant (p < 0.0001) inhibitory activity (IC50 = 
114.842 ± 2.084 µg/mL) compared to Form B (IC50 = 142.829 ± 4.258 µg/mL), though 
weaker than galantamine (IC50 = 27.950 ± 0.122 µg/mL). Form B had significant 
inhibitory effects on BChE (IC50 = 655.860 ± 32.812 µg/mL) compared to Form A 
(IC50 = 679.718 ± 20.656 µg/mL), but lower than galantamine (IC50 = 23.126 ± 
0.683 µg/mL). Both forms protected against Fe2+-mediated brain injury by 
inhibiting MAO. Docking identified quercetin (-10.2 kcal/mol) and myricetin 
(-10.1 kcal/mol) for AChE; rutin (-10.6 kcal/mol) and quercetin (-9.7 kcal/mol) 
for BChE; and kaempferol (-9.1 kcal/mol) and quercetin (-8.9 kcal/mol) for MAO. 
These compounds were thermodynamically stable based on MD analysis. 
Collectively, the results offer a scientific rationale for the use of these 
specifically selected medicinal herbs as AD medications.

DOI: 10.3390/life14101222
PMCID: PMC11508826
PMID: 39459522

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