Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Elife. 2024 Nov 7;13:e100068. doi: 10.7554/eLife.100068.

Host-derived Lactobacillus plantarum alleviates hyperuricemia by improving gut 
microbial community and hydrolase-mediated degradation of purine nucleosides.

Fu Y(1), Luo XD(1), Li JZ(1), Mo QY(1), Wang X(2), Zhao Y(1), Zhang YM(2), Luo 
HT(1), Xia DY(3), Ma WQ(1), Chen JY(1), Wang LH(1), Deng QY(1), Ben L(4), Kashif 
Saleemi M(5), Jiang XZ(6), Chen J(6), Miao K(7), Lin ZP(8), Zhang P(9), Ye H(1), 
Cao QY(1), Zhu YW(1), Yang L(1), Tu Q(10)(11), Wang W(1).

Author information:
(1)State Key Laboratory of Swine and Poultry Breeding Industry, College of 
Animal Science, South China Agricultural University, Guangzhou, China.
(2)State Key Laboratory of Microbial Technology, Shandong University, Shandong, 
China.
(3)School of Marine Sciences, Sun Yat-sen University, and Southern Marine 
Science and Engineering Guangdong Laboratory, Zhuhai, China.
(4)International Livestock Research Institute, Nairobi, Kenya.
(5)Department of Pathology, University of Agriculture Faisalabad, Faisalabad, 
Pakistan.
(6)Microbiome Research Center, Moon (Guangzhou) Biotech Co. Ltd, Guangdong, 
China.
(7)CancerCenter, Faculty of Health Sciences, University of Macau, Macau, China.
(8)Shantou Baisha Research Institute of Origin Species of Poultry and Stock, 
Shantou, China.
(9)Chimelong Safari Park, Chimelong Group Co, Guangzhou, China.
(10)Helmholtz International Lab for Anti-Infectives, Shandong 
University-Helmholtz Institute of Biotechnology, State Key Laboratory of 
Microbial Technology, Shandong University, Qingdao, China.
(11)Shenzhen Key Laboratory of Genome Manipulation and Biosynthesis, CAS Key 
Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic 
Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 
Shenzhen, China.

The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and 
gout. However, it remains unclear whether probiotics residing in the host gut, 
such as Lactobacillus, can prevent HUA development. Herein, we isolated 
Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro 
assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide 
analyses, revealed that this strain may promote nucleoside uptake and hydrolysis 
through its nucleoside hydrolase gene. The functional role of iunH gene was 
confirmed via heterologous expression and gene knockout studies. Oral 
administration of L. plantarum SQ001 resulted in increased abundance of 
Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated 
hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as 
renal reabsorption protein GLUT9, while enhancing the expression of renal 
excretion protein ABCG2. Our findings suggest that L. plantarum has potential to 
ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its 
potential application as a probiotic therapy for individuals with HUA or gout.

Plain Language Summary: Our blood contains many components, including waste 
products that need to be transported to the kidneys, where they can exit the 
body through urine. One such molecule, known as uric acid, forms when cells 
break down old DNA and other similar molecules. This process has several steps, 
with DNA being broken down into intermediate molecules called nucleosides before 
being converted into uric acid. If the amount of uric acid in the bloodstream 
becomes too high (a condition known as hyperuricemia), humans and other animals 
can develop high blood pressure, chronic kidney disease and other illnesses. 
Recent studies suggest that some types of ‘friendly’ bacteria living in the 
human gut may influence how uric acid levels are regulated. But the precise role 
these bacteria play remains unclear. Here, Fu, Luo et al. isolated one of these 
friendly bacterial species, known as Lactobacillus plantarum, from the gut of 
geese with hyperuricemia. The team grew the bacteria in the laboratory in two 
environments: one containing uric acid and the other containing nucleosides. The 
experiments revealed that while Lactobacillus plantarum does not directly act on 
uric acid, it does have enzymes that can convert nucleosides into other 
molecules. Further investigations, using whole-genome and metabolomic analyses, 
showed that Lactobacillus plantarum contains three genes encoding enzymes that 
act on a type of nucleoside known as a purine. Knocking out one of these genes 
prevented the bacteria from being able to convert purines into other molecules. 
Subsequently, Fu, Luo et al. demonstrated that Lactobacillus plantarum helps to 
mitigate the effects of hyperuricemia in geese and mice. These findings provide 
valuable insights into how microbes living in the gut regulate uric acid levels 
in their hosts. They may also inform future strategies for preventing and 
treating hyperuricemia in humans.

© 2024, Fu et al.

DOI: 10.7554/eLife.100068
PMID: 39508089 [Indexed for MEDLINE]

Conflict of interest statement: YF, XL, JL, QM, XW, YZ, YZ, HL, DX, WM, JC, LW, 
QD, LB, MK, KM, ZL, HY, QC, YZ, LY, QT, WW No competing interests declared, XJ, 
JC Affiliated with Biotech Co. Ltd; the author has no financial interests to 
declare, PZ Affiliated with Chimelong Group Co; the author has no financial 
interests to declare


2. Food Chem. 2024 Nov 1;464(Pt 3):141864. doi: 10.1016/j.foodchem.2024.141864. 
Online ahead of print.

In silico identification and experimental validation of two types of 
angiotensin-converting enzyme (ACE) and xanthine oxidase (XO) milk inhibitory 
peptides.

Li Z(1), Zhang W(1), Abubaker MA(1), Shu Q(1), Liu Y(2).

Author information:
(1)College of Food Engineering and Nutritional Science, Shaanxi Normal 
University, Xi'an 710119, Shaanxi, China.
(2)College of Food Engineering and Nutritional Science, Shaanxi Normal 
University, Xi'an 710119, Shaanxi, China. Electronic address: 
yongfeng200@126.com.

Bioactive peptides have received significant attention due to their natural 
origin, low toxicity, and targeting specificity in the past decade. This study 
identified highly active ACE/XO inhibitors using molecular simulation and online 
databases and validated their in vitro antioxidant activity and the mechanisms 
of molecular interactions. According to computer predictions, Asp-Gly-Gly (DGG) 
and Asp-Gly-Met (DGGM) were identified as potential hydrolysates of common 
gastrointestinal peptidases with well water-soluble, non-toxic, and 
non-allergenic. Fourier transform infrared spectroscopy showed that the two 
peptides altered the enzyme's secondary structure, decreasing α-helix content by 
about 13 %, along with increasing β-sheet, randam coli, and β-turns content. 
Molecular docking and molecular dynamics simulations showed that hydrogen 
bonding and electrostatic interactions caused DGG and DGGM to form stable and 
dense complexes with the two enzymes. This study provides a new way for 
economical and efficient screening of new ACE and XO inhibitory peptides from 
natural proteins.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.foodchem.2024.141864
PMID: 39504900

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.


3. Cent Nerv Syst Agents Med Chem. 2024 Nov 4. doi: 
10.2174/0118715249331487241021053730. Online ahead of print.

Antidepressant Potential of Hispidulin Present in S. barbata D. Don: Mechanistic 
Insights through Neurochemical and Behavioral Assessments.

Pannu A(1), Goyal RK(1), Goswami S(1).

Author information:
(1)Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, 
Delhi Pharmaceutical Sciences & Research University, New Delhi-17, India.

BACKGROUND AND AIM: This study aims to investigate the antidepressant properties 
of Hispidulin, a flavonoid present in Scutellaria barbata D. Don. The selection 
of Hispidulin stems from its notable inhibitory activity against Xanthine 
Oxidase (XO), a parameter in the pathophysiology of depression.
MATERIAL AND METHODS: Mice were subjected to a rigorous evaluation using a 
murine model of Chronic Unpredictable Mild Stress (CUMS) to induce depression 
for 21 days and antidepressant properties were rigorously assessed using the 
Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). 
Imipramine and fluoxetine were used as standard drugs. Additionally, 
neurochemical analyses were conducted to quantify serotonin (5-HT), 
norepinephrine (NE), and dopamine (DA) levels in the cortex, hippocampus, and 
hypothalamus. Further mechanistic insights were sought through the estimation of 
monoamine oxidase (MAO) activity and assessment of antioxidant enzyme levels in 
the brain. Plasma nitrite and corticosterone levels were also measured to 
delineate the underlying mechanism of action.
RESULTS: Hispidulin demonstrated significant antidepressant effects, as 
evidenced by reduced immobility time in TST and FST and increased exploratory 
behavior in OFT. Neurochemical analysis revealed restoration of 5-HT, NE, and DA 
levels in key brain regions. Furthermore, Hispidulin modulated MAO activity and 
enhanced antioxidant enzyme levels in the brain. Plasma nitrite levels were 
elevated, indicating enhanced nitric oxide synthesis, while corticosterone 
levels were reduced.
CONCLUSION: Our findings indicate that Hispidulin exerts potent antidepressant 
effects, potentially mediated through its influence on monoaminergic 
neurotransmitters, MAO activity, and antioxidant defenses. These results provide 
valuable mechanistic insights into the antidepressant action of Hispidulin, 
supporting its potential therapeutic application in depressive disorders.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0118715249331487241021053730
PMID: 39501948


4. Cell Death Dis. 2024 Nov 6;15(11):795. doi: 10.1038/s41419-024-07177-5.

Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated 
autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat 
postmenopausal osteoporosis.

Yang K(#)(1), Wang X(#)(1), Zhang C(#)(1), Liu D(1), Tao L(2).

Author information:
(1)Department of Orthopedics, First Hospital of China Medical University, 
Shenyang, China.
(2)Department of Orthopedics, First Hospital of China Medical University, 
Shenyang, China. taolindr@163.com.
(#)Contributed equally

Osteoporosis is a major degenerative metabolic bone disease that threatens the 
life and health of postmenopausal women. Owing to limitations in detection 
methods and prevention strategy awareness, the purpose of osteoporosis treatment 
is more to delay further deterioration rather than to fundamentally correct bone 
mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and 
optimize treatment plans. Our experiments were based on previous findings that 
oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. 
Through energy metabolism-targeted metabolomics, we revealed that purine 
metabolism disorder is the main mechanism involved in inducing oxidative damage 
in bone tissue, which was verified via the use of machine-learning data from 
human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to 
construct a purine metabolism disorder model. The activity and differentiation 
ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing 
indicated that autophagic flux damage was involved in purine metabolism-induced 
oxidative stress in osteoblasts. Additionally, we performed serum metabolomics 
combined with network pharmacology to determine the pharmacological mechanism of 
metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the 
potential target filtered from the hub genes, and FoxO1 signalling was the key 
pathway mediating the effect of metformin in osteoblasts. We also revealed that 
SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to 
increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism 
and prevented the accumulation of ROS caused by purine catabolism to reverse 
oxidative damage in osteoblasts. We propose that purine metabolism 
disorder-induced oxidative stress is important for the pathogenesis of 
postmenopausal osteoporosis. The therapeutic mechanism of metformin should be 
confirmed through subsequent drug optimization and development studies to 
improve bone health in postmenopausal women.

© 2024. The Author(s).

DOI: 10.1038/s41419-024-07177-5
PMCID: PMC11538437
PMID: 39500875 [Indexed for MEDLINE]

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


5. Pak J Pharm Sci. 2024 Sep;37(5):1151-1161.

Novel pyrimidine derivatives and black cumin as xanthine oxidase inhibitors: 
Synthesis, docking study and formulation.

Ahjel SW(1), Humadi SS(1), Mohamed Awad S(2), El-Shehry MF(3), Mansour YE(4), 
El-Rashedy AAE(5).

Author information:
(1)Pharmacy Department, Al-Zahrawi University College, Karbala, Iraq.
(2)Pharmacy Department, Al-Zahrawi University College, Karbala, 
Iraq/Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Helwan, Egypt.
(3)Pharmacy Department, Al-Zahrawi University College, Karbala, Iraq/Pesticides 
Chemistry Department, National Research Centre, Dokki, Giza, Egypt.
(4)Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Helwan, Egypt.
(5)Chemistry of Natural and Microbial Products, National Research Centre, Dokki, 
Giza, Egypt.

In this work, to attempt discovery of novel xanthine oxidase (XO) inhibitors, we 
developed a method for optimizing the Nigella sativa oil extraction by 
considering the seed size particles, the liquid seed ratio, the duration of the 
extraction procedure and the temperature of extraction. On the other hand, new 
pyrimidine and triazolopyrimidine derivatives were prepared in an attempt to 
mimic the pyrazolpyrimidine structure of allopurinol (a well-known xanthine 
oxidase inhibitor drug). Most of the developed compounds were shown to have 
strong xanthine oxidase inhibitory activities, while Nigella sative extract and 
compound 6b ranked as the most effective inhibitors (IC50=1.87 and 0.63μg/ml, 
respectively, versus Allupurinol's IC50=0.62μg/ml). Nigella sative extract and 
compound 6b showed potent activity (IC50=0.60μg/ml). In addition, compound 6b 
was formulated as effervescent granules and exhibited good flow-ability 
properties. To further understand the approach of binding between synthesized 
compounds 6a-c and xanthine oxidase, a molecular docking investigation was 
conducted. These findings highlight the discovery of a novel group of xanthine 
oxidase inhibitors with the potential to improve the state-of-the-art treatment 
for gout.

PMID: 39495856 [Indexed for MEDLINE]