Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Food Res Int. 2024 Oct;193:114857. doi: 10.1016/j.foodres.2024.114857. Epub
2024  Aug 2.

Exploration of the mechanism of temperature influence on bitter taste of 
theacrine by activating human bitter taste receptor hTAS2R14.

Xie J(1), Wen H(2), Shi Y(3), Wei F(1), Jiang J(4), Luo L(5), Zeng L(6).

Author information:
(1)Integrative Science Center of Germplasm Creation in Western China (CHONGQING) 
Science City, College of Food Science, Southwest University, Chongqing 400715, 
China; Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and 
Chongqing, Southwest University, Chongqing 400715, China; Chongqing Tea 
Technology and Innovation Center, China.
(2)National Research Center of Engineering and Technology for Utilization of 
Botanical Functional Ingredients, Hunan Agricultural University, Changsha 
410128, China.
(3)Modern Logistics of China Railway No.8 Engineering Group CO., LTD, Chengdu 
610306, Sichuan, China.
(4)Integrative Science Center of Germplasm Creation in Western China (CHONGQING) 
Science City, College of Food Science, Southwest University, Chongqing 400715, 
China; Dayi Tea Group Menghai Tea Factory Co., Yunnan 666100, China.
(5)Integrative Science Center of Germplasm Creation in Western China (CHONGQING) 
Science City, College of Food Science, Southwest University, Chongqing 400715, 
China; Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and 
Chongqing, Southwest University, Chongqing 400715, China; Chongqing Tea 
Technology and Innovation Center, China. Electronic address: 467002526@qq.com.
(6)Integrative Science Center of Germplasm Creation in Western China (CHONGQING) 
Science City, College of Food Science, Southwest University, Chongqing 400715, 
China; Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and 
Chongqing, Southwest University, Chongqing 400715, China; Chongqing Tea 
Technology and Innovation Center, China. Electronic address: 
zengliangbaby@126.com.

Theacrine, a purine alkaloid derived from Camellia assamica var. kucha, has a 
distinct bitter taste. Our previous study found the lower recognition threshold 
of theacrine at 25 °C than 45 °C. This study aims to investigate the bitterness 
characterizations of theacrine at aforementioned temperatures and its taste 
perception mechanism. Sensory analysis exhibited higher bitterness intensity for 
theacrine at 25 °C than 45 °C. Subsequently, flow cytometry was performed to 
verify the above characterization at the cellular level. It revealed that 
theacrine could activated the bitter receptor hTAS2R14 and the calcium signal at 
25 °C was higher than 45 °C. Ultimately, the interaction mechanism was studied 
by molecular dynamics simulations, indicating that the conformation of 
theacrine-hTAS2R14 had a higher binding capacity and better stability at 25 °C. 
Overall, temperature affected the binding of theacrine to the bitter receptor 
hTAS2R14, resulting in the stronger bitterness intensity of theacrine at 25 °C 
than 45 °C.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.foodres.2024.114857
PMID: 39160053 [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.


2. 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.


3. Int J Rheum Dis. 2024 Feb;27(2):e15085. doi: 10.1111/1756-185X.15085.

Theacrine enhances autophagy and inhibits inflammation via regulating 
SIRT3/FOXO3a/Parkin pathway.

Li J(1), Yan W(1), Yuan H(1), Ren F(1).

Author information:
(1)Department of Dermatology, Jinling Hospital, Affiliated Hospital of Medical 
School, Nanjing University, Nanjing, China.

BACKGROUND: Psoriasis, a common chronic inflammatory skin condition, impacts 
around 2%-3% of the global population. Theacrine is recognized for its potential 
anti-inflammatory and antioxidant properties. However, the role of theacrine in 
psoriasis remains unclear.
PURPOSES: To investigate the effects of theacrine on psoriasis and explore the 
underlying signaling pathways.
METHODS: For imiquimod (IMQ)-induced Psoriasis-like mice, the psoriatic 
inflammation was monitored using Psoriasis Area and Severity Index (PASI). The 
skin damage was observed using Hematoxylin and Eosin staining. The KI67 and CD4 
in skin tissues were assessed using Immunohistochemistry analysis. Western blots 
were performed to evaluate the expression of Keratin 1 (KRT1), KRT6, LC3, P62, 
Beclin1, T-bet, GATA3, RAR-related orphan receptor (ROR)-γt, Sirtuin-3 (SIRT3), 
Forkhead Box O3a (FOXO3a) and Parkin. Additionally, LC3B expression was analyzed 
using an immunofluorescent assay, while flow cytometry was performed to analyze 
the percentage of Th17, Th1, and Th2 positive cells in skin-draining lymph node.
RESULTS: Theacrine improved skin condition by reducing hyperkeratosis and 
acanthosis, lowering PASI scores, and decreasing KI67-positive cells. Theacrine 
also modulated keratin expression, elevating KRT1 while reducing KRT6 levels. 
Theacrine enhanced autophagy indicated by an increased LC3-II/LC3-I ratio and 
Beclin1, while reduced P62 levels. Additionally, Theacrine reduced CD4-positive 
cells and suppressed Th17 and Th1 cell activation. Theacrine activated the 
FOXO3a/Parkin pathway by upregulating SIRT3 expression, and down-regulation of 
SIRT3 counteracted theacrine's effects in psoriasis-like mice.
CONCLUSION: Theacrine inhibits skin damage, promotes autophagy, and mediates 
inflammation in IMQ-induced psoriasis mice via upregulating SIRT3 to activate 
FOXO3a/Parkin pathway, positioning theacrine as a candidate for psoriasis 
treatment.

© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & 
Sons Australia, Ltd.

DOI: 10.1111/1756-185X.15085
PMID: 38402443 [Indexed for MEDLINE]


4. Ren Fail. 2024 Dec;46(1):2314637. doi: 10.1080/0886022X.2024.2314637. Epub
2024  Feb 21.

Risk factors and renal outcomes of AKI in children with secondary 
steroid-resistant nephrotic syndrome.

Yu N(1), Ouyang X(1), Li J(1), Gao J(1), Zeng S(1), Zhuang H(1), Jiang M(1), Pei 
Y(1), Jiang X(1).

Author information:
(1)Department of Pediatric Nephrology and Rheumatology, The First Affiliated 
Hospital, Sun Yat-sen University, Guangzhou, P.R. China.

BACKGROUND: Acute kidney injury (AKI) is increasingly prevalent in children with 
nephrotic syndrome (NS). It is associated with adverse outcomes in NS, 
especially steroid-resistant nephrotic syndrome (SRNS). The incidence, risk 
factors and outcomes of AKI in secondary SRNS remain undefined. The main 
objectives of this study were to determine the risk factors and prognosis of AKI 
in hospitalized children with secondary SRNS.
MATERIAL AND METHODS: This retrospective study was conducted from January 2014 
to December 2019, involving 172 hospitalizations with secondary SRNS admitted to 
the First Affiliated Hospital of Sun Yat-sen University. AKI was defined and 
classified in accordance with the 2012 Kidney Disease Improving Global Outcomes 
(KDIGO) guidelines.
RESULTS: AKI was found in 67 (39.0%) of 172 hospitalizations with secondary 
SRNS. Average age of onset in our group is 4.4 (3.1, 6.7) years with AKI and 3.7 
(1.8, 5.6) years without AKI. Urea nitrogen level is 5.9 (4.1, 10.0) mmol/L with 
AKI and 5.1 (3.7, 7.0) mmol/L. Uric acid level is 446.0 (340.0, 567.0) umol/L 
with AKI and 401.0 (303.0, 496.0) umol/L. 24-h urinary protein level is 4.14 
(2.9, 6.5) g with AKI and 2.5 (1.3, 5.3) without AKI. Multivariate logistic 
regression revealed that infection (OR = 5.287; 95% confidence interval, 2.349 
to 11.899; p < 0.001), age at onset (OR = 1.180; 95% confidence interval, 1.032 
to 1.349; p = 0.015) and uric acid level (OR = 1.003; 95% confidence interval, 
1.000 to 1.006; p = 0.031) were significantly associated with the development of 
AKI in children with secondary SRNS. Among 72 children with secondary SRNS, six 
went to end-stage kidney disease (ESKD). Children in the AKI group were more 
likely to progress to ESKD compared with children in the non-AKI group 
(p = 0.017) with a median follow-up of 48.5months.
CONCLUSION: AKI occurred in 39.0% of total hospitalizations associated with 
secondary SRNS. Risk factors including infection, age of onset, and uric acid 
level are associated with AKI in children with secondary SRNS. Furthermore, AKI 
was identified as a risk factor for the progression of secondary SRNS to ESKD.

DOI: 10.1080/0886022X.2024.2314637
PMCID: PMC10885744
PMID: 38383285 [Indexed for MEDLINE]

Conflict of interest statement: No potential conflict of interest was reported 
by the authors.


5. Intern Med. 2024 Jun 1;63(11):1539-1548. doi:
10.2169/internalmedicine.2474-23.  Epub 2023 Oct 20.

J-shaped Association between Serum Uric Acid Levels and the Prevalence of a 
Reduced Kidney Function: A Cross-sectional Study Using Japanese Health 
Examination Data.

Kawasoe S(1), Kubozono T(1), Salim AA(1), Ojima S(1), Yamaguchi S(1), Ikeda 
Y(1), Miyahara H(2), Tokushige K(2), Ohishi M(1).

Author information:
(1)Department of Cardiovascular Medicine and Hypertension, Graduate School of 
Medical and Dental Sciences, Kagoshima University, Japan.
(2)Kagoshima Kouseiren Hospital, Japan.

Objective While an association between a reduced kidney function and 
hyperuricemia has been reported, its association with hypouricemia is not well 
understood. The present study therefore investigated this association. Methods 
Using a large Japanese health examination dataset, we performed a multivariable 
logistic regression analysis to assess the association between serum uric acid 
(SUA) levels and a reduced kidney function. The covariates included the age, 
body mass index, alcohol intake, and the presence of hypertension, dyslipidemia, 
or diabetes. Patients This study included 227,672 patients (104,854 men; 46.1%), 
and the analyses were performed separately for men and women. The patients were 
classified into 5 groups: hypouricemia (SUA ≤2.0 mg/dL) (1st) and four other 
(2nd-5th) groups with SUA levels of ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL 
in men and ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL in women, respectively. 
Results The characteristics of the study population were as follows: men, age 
55.9±14.9 years old, SUA 5.9±1.3 mg/dL, estimated glomerular filtration rate 
(eGFR) 80.0±17.2 mL/min/1.73 m2, and a reduced kidney function (eGFR <60.0 
mL/min/1.73 m2) 9.4%; women, age 57.3±15.0 years old, SUA 4.5±1.1 mg/dL, eGFR 
81.2±18.0 mL/min/1.73 m2, and a reduced kidney function 9.4%. Compared with the 
2nd group, the other 4 groups groups had a significantly higher prevalence of a 
reduced kidney function [odds ratio (OR), 2.58; 95% confidence interval (CI), 
1.64-4.06 in men; OR, 1.66; 95% CI, 1.16-2.39 in women]. Conclusion The 
prevalence of a reduced kidney function was high in both men and women in the 
hypouricemia and high-SUA groups. SUA levels and the prevalence of a reduced 
kidney function showed a J-shaped association.

DOI: 10.2169/internalmedicine.2474-23
PMCID: PMC11189714
PMID: 37866917 [Indexed for MEDLINE]

Conflict of interest statement: The authors state that they have no Conflict of 
Interest (COI).