Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. mSystems. 2024 Jul 23;9(7):e0130123. doi: 10.1128/msystems.01301-23. Epub 2024
 Jun 20.

Gut-derived metabolite 3-methylxanthine enhances cisplatin-induced apoptosis via 
dopamine receptor D1 in a mouse model of ovarian cancer.

Mai Z(#)(1)(2), Han Y(#)(2), Liang D(#)(2), Mai F(3), Zheng H(4), Li P(5), Li 
Y(2), Ma C(2), Chen Y(2), Li W(2), Zhang S(2), Feng Y(6), Chen X(4), Wang Y(1).

Author information:
(1)Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical 
University, Guangzhou, China.
(2)Department of Obstetrics & Gynecology, First people's hospital of Foshan, 
Foshan, China.
(3)Institute of Ecological Sciences, School of Life Sciences, South China Normal 
University, Guangzhou, China.
(4)Department of Obstetrics and Gynecology, The First Affiliated Hospital of 
Ningbo University, Ningbo, Zhejiang Province, China.
(5)Microbiome Research Centre, St. George and Sutherland Clinical School, UNSW, 
Sydney, New South Wales, Australia.
(6)Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare 
Hospital, Southern Medical University, Foshan, China.
(#)Contributed equally

Platinum-based chemotherapy failure represents a significant challenge in the 
management of ovarian cancer (OC) and contributes to disease recurrence and poor 
prognosis. Recent studies have shed light on the involvement of the gut 
microbiota in modulating anticancer treatments. However, the precise underlying 
mechanisms, by which gut microbiota regulates the response to platinum-based 
therapy, remain unclear. Here, we investigated the role of gut microbiota on the 
anticancer response of cisplatin and its underlying mechanisms. Our results 
demonstrate a substantial improvement in the anticancer efficacy of cisplatin 
following antibiotic-induced perturbation of the gut microbiota in OC-bearing 
mice. 16S rRNA sequencing showed a pronounced alteration in the composition of 
the gut microbiome in the cecum contents following exposure to cisplatin. 
Through metabolomic analysis, we identified distinct metabolic profiles in the 
antibiotic-treated group, with a notable enrichment of the gut-derived 
metabolite 3-methylxanthine in antibiotic-treated mice. Next, we employed a 
strategy combining transcriptome analysis and chemical-protein interaction 
network databases. We identified metabolites that shared structural similarity 
with 3-methylxanthine, which interacted with genes enriched in cancer-related 
pathways. It is identified that 3-methylxanthinesignificantly enhances the 
effectiveness of cisplatin by promoting apoptosis both in vivo and in vitro. 
Importantly, through integrative multiomics analyses, we elucidated the 
mechanistic basis of this enhanced apoptosis, revealing a dopamine receptor 
D1-dependent pathway mediated by 3-methylxanthine. This study elucidated the 
mechanism by which gut-derived metabolite 3-methylxanthine mediated 
cisplatin-induced apoptosis. Our findings highlight the potential translational 
significance of 3-methylxanthine as a promising adjuvant in conjunction with 
cisplatin, aiming to improve treatment outcomes for OC patients.IMPORTANCEThe 
precise correlation between the gut microbiota and the anticancer effect of 
cisplatin in OC remains inadequately understood. Our investigation has revealed 
that manipulation of the gut microbiota via the administration of antibiotics 
amplifies the efficacy of cisplatin through the facilitation of apoptosis in 
OC-bearing mice. Metabolomic analysis has demonstrated that the cecum content 
from antibiotic-treated mice exhibits an increase in the levels of 
3-methylxanthine, which has been shown to potentially enhance the therapeutic 
effectiveness of cisplatin by an integrated multiomic analysis. This enhancement 
appears to be attributable to the promotion of cisplatin-induced apoptosis, with 
3-methylxanthine potentially exerting its influence via the dopamine receptor 
D1-dependent pathway. These findings significantly contribute to our 
comprehension of the impact of the gut microbiota on the anticancer therapy in 
OC. Notably, the involvement of 3-methylxanthine suggests its prospective 
utility as a supplementary component for augmenting treatment outcomes in 
patients afflicted with ovarian cancer.

DOI: 10.1128/msystems.01301-23
PMCID: PMC11264688
PMID: 38899930 [Indexed for MEDLINE]

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


2. MedComm (2020). 2024 Jun 17;5(7):e617. doi: 10.1002/mco2.617. eCollection 2024
 Jul.

Metabolic shifts during coffee consumption refresh the immune response: insight 
from comprehensive multiomics analysis.

Ruan P(1), Yang M(1), Lv X(1), Shen K(1), Chen Y(2), Li H(3), Zhao D(4), Huang 
J(4), Xiao Y(5), Peng W(3), Wu H(1), Lu Q(1)(2)(6)(7).

Author information:
(1)Department of Dermatology The Second Xiangya Hospital, Central South 
University Hunan Key Laboratory of Medical Epigenomics Changsha China.
(2)Hospital for Skin Diseases Institute of Dermatology Chinese Academy of 
Medical Sciences and Peking Union Medical College Nanjing China.
(3)Department of Integrated Traditional Chinese and Western Medicine The Second 
Xiangya Hospital Central South University Changsha China.
(4)Hunan Academy of Chinese Medicine Hunan University of Chinese Medicine 
Changsha China.
(5)National Clinical Research Center for Metabolic Diseases The Second Xiangya 
Hospital, Central South University Changsha China.
(6)Key Laboratory of Basic and Translational Research on Immune-Mediated Skin 
Diseases Chinese Academy of Medical Sciences Nanjing China.
(7)Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs 
Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union 
Medical College Nanjing China.

Coffee, a widely consumed beverage, has shown benefits for human health but 
lacks sufficient basic and clinical evidence to fully understand its impacts and 
mechanisms. Here, we conducted a cross-sectional observational study of coffee 
consumption and a 1-month clinical trial in humans. We found that coffee 
consumption significantly reshaped the immune system and metabolism, including 
reduced levels of inflammatory factors and a reduced frequency of senescent T 
cells. The frequency of senescent T cells and the levels of the 
senescence-associated secretory phenotype were lower in both long-term coffee 
consumers and new coffee consumers than in coffee nondrinking subjects, 
suggesting that coffee has anti-immunosenescence effects. Moreover, coffee 
consumption downregulated the activities of the The Janus kinase/signal 
transduction and activator of transcription (JAK/STAT) and mitogen-activated 
protein kinases (MAPK) signaling pathways and reduced systemic proinflammatory 
cytokine levels. Mechanistically, coffee-associated metabolites, such as 
1-methylxanthine, 3-methylxanthine, paraxanthine, and ceramide, reduced the 
frequency of senescent CD4+CD57+ T cells in vitro. Finally, in vivo, coffee 
intake alleviated inflammation and immunosenescence in imiquimod-induced 
psoriasis-like mice. Our results provide novel evidence of the anti-inflammatory 
and anti-immunosenescence effects of coffee, suggesting that coffee consumption 
could be considered a healthy habit.

© 2024 The Author(s). MedComm published by Sichuan International Medical 
Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

DOI: 10.1002/mco2.617
PMCID: PMC11181901
PMID: 38887468

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


3. J Med Virol. 2024 Jun;96(6):e29723. doi: 10.1002/jmv.29723.

Circulating metabolites are associated with persistent elevations of ALT in 
patients with chronic hepatitis B with complete viral suppression.

Zheng D(1), Cheng C(1), Tang Y(2), Fang Z(1), Gao X(1), Chen Y(1), You Q(1), 
Wang K(1), Zhou H(1), Lan Z(1), Sun J(1).

Author information:
(1)State Key Laboratory of Organ Failure Research, Key Laboratory of Infectious 
Diseases Research in South China, Ministry of Education, Guangdong Provincial 
Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical 
Research Center for Viral Hepatitis, Guangdong Institute of Hepatology, 
Department of Infectious Diseases, Nanfang Hospital, Southern Medical 
University, Guangzhou, China.
(2)Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Hengyang 
Medical School, University of South China, Hengyang, China.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; 
however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine 
aminotransferase (ALT) levels and sustained disease progression. This study 
provides novel insights into the mechanism and potential predictive biomarkers 
of persistently elevated ALT (PeALT) in patients with CHB after complete viral 
inhibition. Patients having CHB with undetectable HBV DNA at least 12 months 
after antiviral treatment were enrolled from a prospective, observational 
cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 
using propensity score matching. Correlations between plasma metabolites and the 
risk of elevated ALT were examined using multivariate logistic regression. A 
mouse model of carbon tetrachloride-induced liver injury was established to 
validate the effect of key differential metabolites on liver injury. Of the 1238 
patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT 
levels during follow-up (median follow-up: 2.42 years). Additionally, 40 
patients with PnALT levels were matched as controls. Ser-Phe-Ala, 
Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine 
were identified as critical differential metabolites between the two groups and 
independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels 
could be used to discriminate patients with PeALT from those with PnALT. 
Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative 
correlation with ALT levels. NALM supplementation alleviated liver injury and 
hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating 
metabolites may contribute to PeALT levels in patients with CHB who have 
achieved complete viral suppression after antiviral treatment.

© 2024 Wiley Periodicals LLC.

DOI: 10.1002/jmv.29723
PMID: 38828911 [Indexed for MEDLINE]


4. Clin Nutr. 2024 Jun;43(6):1584-1592. doi: 10.1016/j.clnu.2024.05.004. Epub
2024  May 7.

Association between caffeine metabolites in urine and muscle strength in young 
and older adults: A cross-sectional study from NHANES 2011-2012.

Batista-da-Silva B(1), Limirio LS(1), de Oliveira EP(2).

Author information:
(1)Laboratory of Nutrition, Exercise and Health (LaNES), School of Medicine, 
Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil.
(2)Laboratory of Nutrition, Exercise and Health (LaNES), School of Medicine, 
Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil. 
Electronic address: erick_po@yahoo.com.br.

BACKGROUND: Elevated levels of reactive oxygen species may contribute to the 
gradual decline in muscle strength over time. Although caffeine and its 
metabolites have antioxidant properties that can mitigate oxidative stress, the 
association of caffeine and its metabolites with muscle strength remains 
unknown.
AIM: To investigate whether caffeine metabolites in urine are associated with 
muscle strength in young and older adults.
METHODS: A cross-sectional study was conducted with 1145 individuals aged over 
20 years (n = 801 < 60 years and n = 344 ≥ 60 years) from the National Health 
and Nutrition Examination Survey (NHANES) 2011-2012. Muscle strength was 
assessed using a handgrip dynamometer, and combined grip strength was determined 
by summing the highest value from each hand. Caffeine and its metabolites in 
urine were quantified using ultra-high-performance liquid 
chromatography-electrospray ionization-tandem mass spectrometry (1-methyluric 
acid, 3-methyluric acid, 7-methyluric acid, 1,3-dimethyluric acid, 
1,7-dimethyluric acid, 3,7-dimethyluric acid, 1,3,7-trimethyluric acid, 
1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 
1,7-dimethylxanthine, 3,7-dimethylxanthine, 1,3,7-trimethylxanthine, 
5-acetylamino-6-amino-3-methyluracil). Linear regression analyses were performed 
to determine the association of caffeine and its metabolites with muscle 
strength in young and older adults, adjusting for confounders.
RESULTS: Positive associations between muscle strength and levels of 
7-methyluric acid (β = 0.029; p = 0.021), 1,3-dimethyluric acid (β = 0.008; 
p = 0.004), 3,7-dimethyluric acid (β = 0.645; p = 0.012), 3-methylxanthine 
(β = 0.020; p = 0.002), 7-methylxanthine (β = 0.020; p = 0.006), 
1,3-dimethylxanthine (theophylline) (β = 0.030; p = 0.004) and 
3,7-dimethylxanthine (theobromine) (β = 0.035; p = 0.029) were observed in older 
adults. In contrast, no such associations were noted in young adults.
CONCLUSION: Our study indicates a positive association between certain caffeine 
metabolites in urine and muscle strength in older adults, but not in younger 
individuals. These findings indicate that specific caffeine metabolites may 
contribute to an antioxidant role especially in older adults.

Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and 
Metabolism. All rights reserved.

DOI: 10.1016/j.clnu.2024.05.004
PMID: 38759491 [Indexed for MEDLINE]

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


5. J Chromatogr A. 2024 Jul 5;1726:464973. doi: 10.1016/j.chroma.2024.464973.
Epub  2024 May 7.

Insights into the selectivity of polar stationary phases based on quantitative 
retention mechanism assessment in hydrophilic interaction chromatography.

Guo Y(1), Baran D(2), Ryan L(2).

Author information:
(1)School of Pharmacy and Health Sciences, Fairleigh Dickinson University, 230 
Park Ave. Florham Park, New Jersey 07932, USA. Electronic address: 
yongguo@fdu.edu.
(2)School of Pharmacy and Health Sciences, Fairleigh Dickinson University, 230 
Park Ave. Florham Park, New Jersey 07932, USA.

Hydrophilic interaction chromatography (HILIC) offers different selectivity than 
reversed-phase liquid chromatography (RPLC). However, our knowledge of the 
driving force for selectivity is limited and there is a need for a better 
understanding of the selectivity in HILIC. Quantitative assessment of retention 
mechanisms makes it possible to investigate selectivity based on understanding 
the underlying retention mechanisms. In this study, selected model compounds 
from the Ikegami selectivity tests were evaluated on different polar stationary 
phases. The study results revealed significant insights into the selectivity in 
HILIC. First, hydroxy and methylene selectivity is driven by hydrophilic 
partitioning; but surface adsorption for 2-deoxyuridine or 5-methyluridine 
reduces the selectivity factor. Furthermore, the retention of 2-deoxyuridine or 
5-methyluridine by surface adsorption in combination with the phase ratio 
explain the difference in hydroxy or methylene selectivity observed among 
different stationary phases. Investigations on xanthine positional isomers 
(1-methylxanthine/3-methylxanthine, theophylline/theobromine) indicate that 
isomeric selectivity is controlled by surface adsorption; however, hydrophilic 
partitioning may contribute to resolution by enhancing overall retention. In 
addition, two pairs of nucleoside isomers (adenosine/vidarabine, 2'-deoxy and 
3'-deoxyguanosine) provide an example that isomeric selectivity can also be 
controlled by hydrophilic partitioning if their partitioning coefficients are 
significantly different in HILIC. Although more data is needed, the current 
study provides a mechanistic based understanding of the selectivity in HILIC and 
potentially a new way to design selectivity tests.

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

DOI: 10.1016/j.chroma.2024.464973
PMID: 38729044 [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.