Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. BMC Complement Med Ther. 2024 Nov 6;24(1):384. doi:
10.1186/s12906-024-04618-8.

Population-pharmacokinetic/pharmacodynamic model of atractylodes lancea (Thunb.) 
DC. administration in patients with advanced-stage intrahepatic 
cholangiocarcinoma: a dosage prediction.

Saeheng T(1)(2), Karbwang J(3), Na-Bangchang K(4)(5)(6).

Author information:
(1)Centre of Excellence in Pharmacology and Molecular Biology of Malaria and 
Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat 
University (Rangsit Campus), 99, moo 18, Phaholyothin Road, Klongneung 
sub-district, Klongluang district, Pathumthani, 12121, Thailand.
(2)Graduate Program in Bioclinical Sciences, Chulabhorn International College of 
Medicine, Thammasat University, Klongluang, Pathumthani, 12120, Thailand.
(3)Drug Discovery and Development Centre, Office of Advanced Science and 
Technology, Thammasat University (Rangsit Campus), Klongluang, Pathumthani, 
Thailand.
(4)Centre of Excellence in Pharmacology and Molecular Biology of Malaria and 
Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat 
University (Rangsit Campus), 99, moo 18, Phaholyothin Road, Klongneung 
sub-district, Klongluang district, Pathumthani, 12121, Thailand. 
kesaratmu@yahoo.com.
(5)Graduate Program in Bioclinical Sciences, Chulabhorn International College of 
Medicine, Thammasat University, Klongluang, Pathumthani, 12120, Thailand. 
kesaratmu@yahoo.com.
(6)Drug Discovery and Development Centre, Office of Advanced Science and 
Technology, Thammasat University (Rangsit Campus), Klongluang, Pathumthani, 
Thailand. kesaratmu@yahoo.com.

BACKGROUND: A recent phase 2A clinical study of Atractylodes lancea (Thunb.) DC. 
(AL) in patients with advanced-stage intrahepatic cholangiocarcinoma (iCCA) 
demonstrated significant reduction of the risk of tumor progression and 
mortality with a dose ranging from 1,000 to 2,000 mg. The present study aimed to 
determine the potential dosage regimen of AL for further phase 2B clinical 
study.
METHODS: Plasma-concentration time profiles of total AL bioactivity and clinical 
efficacy in patients with advanced-stage iCCA were obtained from Phase 2 A 
study. The population pharmacokinetic (pop-PK) model was developed. The pop-PK 
model and Monte-Carlo (MC) simulation, in conjunction with maximum concentration 
of AL (Cmax) as a cut-off criterion, was performed and validated with clinical 
data. The optimal model was used to simulate further dosage regimens and 
clinical efficacy of AL.
RESULTS: The pop-PK properties of total AL bioactivity were best described by a 
compartmental model with zero-order absorption (without delay) and linear 
clearance. None of the investigated covariates improved model accuracy.The 
developed pop-PK with MC simulations following once-daily dosing of 1,000 mg and 
2,000 mg adequately predicted the clinical efficacy (tumor progression and 
mortality). The once-daily dose of 2,500 mg is recommended for further phase 2B 
clinical study due to its relatively high efficacy on tumor progression 
inhibition (73%) and mortality rate reduction (71%) without excessive number of 
the administered capsules (23 capsules) and low risk of toxicities (<5%).
CONCLUSIONS: The applied pop-PK model with MC simulation, along with the 
appropriate cut-off pharmacokinetic parameters, can be used as a potential tool 
for supporting dosage prediction and selection for clinical studies, and thus 
reducing the rate of drug development failures.
TRIAL REGISTRATION: www.thaiclinicaltrials.org , WHO ICTRP search, 
TCTR20210129007 , Registed 29 January 2021.

© 2024. The Author(s).

DOI: 10.1186/s12906-024-04618-8
PMID: 39508255


2. BMC Public Health. 2024 Nov 6;24(1):3064. doi: 10.1186/s12889-024-20557-y.

Longitudinal policy surveillance of state obesity legislation in California, 
1999-2020.

Payán DD(1), Chan-Golston AM(2), Garibay KK(2), Farias C(3).

Author information:
(1)Department of Health, Society and Behavior, Joe C. Wen School of Population & 
Public Health, University of California, Irvine, 856 Health Sciences Quad, 
Irvine, CA, 92697-3957, USA. dpayan@hs.uci.edu.
(2)Department of Public Health, School of Social Sciences, Humanities, and Arts, 
University of California, Merced, 5200 North Lake Rd, Merced, CA, 95343, USA.
(3)Department of Public Health, School of Social Sciences, Humanities, and Arts, 
University of California, Merced, 5200 North Lake Rd, Merced, CA, 95343, USA. 
cfarias4@ucmerced.edu.

BACKGROUND: Obesity rates among children and adults continue to accelerate in 
the U.S., particularly among marginalized and low-income populations. Obesity 
prevention and reduction policies can significantly impact population health by 
improving environmental conditions and increasing access to health-promoting 
resources. Limited research has been conducted to examine state obesity policy 
change over time. The primary aim of this study is to examine legislative 
approaches used to prevent and reduce obesity in the state of California (U.S.).
METHODS: We used quantitative policy surveillance methods to develop a state 
database of obesity-related legislation (bills, resolutions) introduced in 
California's legislature between 1999 and 2020. Descriptive statistics were used 
to examine trends of introduced and enacted policy by legislative and policy 
characteristics. Chi-square tests were used to determine differences in 
characteristics between enacted and non-enacted legislation. Legislative session 
and policy characteristics found to be associated with enactment were used to 
predict adoption in a logistic regression.
RESULTS: A total of 284 obesity-related bills and resolutions were introduced in 
California's legislature between 1999 and 2020 with a peak of 43 in 2005-2006. 
On average, 25.8 bills and resolutions were introduced each 2-year legislative 
cycle. Findings indicate that (a) children and schools were the most frequently 
specified population and setting; (b) the most common policy topics were 
nutrition (45%) and physical activity (33%); and (c) only 15% of legislation 
mentioned race/ethnicity. Overall, 24.9% of bills were enacted compared to 82.1% 
of resolutions adopted. Legislation to raise awareness about obesity had 5.4 
times the odds of being passed compared to other topics. Yet this difference was 
not statistically significant in a sensitivity analysis when we excluded 
resolutions.
CONCLUSIONS: This database can be leveraged to advance our knowledge of 
effective and equitable policy instruments to prevent and reduce obesity. 
Results reveal important policy elements that may impact legislative success, 
including policy topic, and contribute to a nascent evidence base for public 
health law research, legal epidemiology, and practice. Future work should 
investigate the role of policy effectiveness research and evidence on 
legislative policymaking.

© 2024. The Author(s).

DOI: 10.1186/s12889-024-20557-y
PMID: 39508251


3. HIV Med. 2024 Nov 7. doi: 10.1111/hiv.13730. Online ahead of print.

Burden of liver steatosis and liver fibrosis in a large cohort of people living 
with HIV.

Laguno M(1)(2)(3), de Lazzari E(1)(2)(3), Berrocal L(1)(2), Inciarte A(1)(2)(3), 
Martínez-Rebollar M(1), de la Mora L(1), Torres B(1)(2)(3), Gonzalez-Cordón 
A(1), Chivite I(1), Foncillas A(1), Calvo J(1), Sempere A(1), Ambrosioni 
J(1)(2)(3), Blanco JL(1)(2)(3), Miro JM(1)(2)(3), Mallolas J(1)(2)(3), Martínez 
E(1)(2)(3).

Author information:
(1)HIV Unit, Infectious Diseases Service. Hospital Clínic of Barcelona, 
Barcelona, Spain.
(2)Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques 
August Pi I Sunyer. (IDIBAPS), Barcelona, Spain.
(3)Centro de Investigación Biomédica en Red, CIBERINFEC, Madrid, Spain.

BACKGROUND: Liver steatosis (LS) and liver fibrosis (LF) can increase the risk 
of cardiovascular disease in people with HIV, but their prevalence and 
associated factors are poorly understood. This study aimed to assess the 
prevalence of and factors associated with LS and LF in a large cohort of people 
with HIV.
METHODS: We conducted a cross-sectional study of consecutive people with HIV 
attending the Clinic of Barcelona from September 2022 to September 2023, 
excluding those with chronic B or/and C hepatitis virus coinfection. LS was 
assessed using the Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI), 
and LF was assessed using the Non-Alcoholic Fatty Liver Disease Fibrosis Score 
(NFS), Fibrosis-4 score (FIB-4), and the European AIDS Clinical Society (EACS) 
algorithm in both the whole cohort (cohort 1) and in a specific cohort more 
susceptible to liver disease (cohort 2). We identified independent variables 
associated with LS and LF using logistic regression.
RESULTS: Cohort 1 included 4664 people with HIV; 76% and 37% of them had 
available HSI and FLI data, LS was present in 28% and 19%, respectively. LF risk 
was present in 1%, 2%, and 1% of people with HIV according to NFS, FIB-4, and 
EACS algorithm scores, respectively. Cohort 2 included 1345 people with HIV; 60% 
and 30% of them had available HSI and FLI data, LS affected 55% and 43% and LF 
2%, 5%, or 3%, respectively. Factors associated with LS included current CD4 
cell count, diabetes, and hypertension, whereas LF was associated with previous 
exposure to dideoxynucleoside drugs and current CD4 to LF. Current integrase 
strand transfer inhibitor (INSTI) therapy appeared protective for LF in cohort 
1.
CONCLUSIONS: In this study, one in four people with HIV had LS, and the 
prevalence rose to one in two in those with cardiovascular risk factors. The 
prevalence of LF was low, but it should be considered in older people with HIV 
with low CD4 counts or high aspartate transaminase levels. A possible protective 
effect from INSTIs deserves further investigation.

© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf 
of British HIV Association.

DOI: 10.1111/hiv.13730
PMID: 39508213


4. RNA Biol. 2024 Jan;21(1):70-81. doi: 10.1080/15476286.2024.2417152. Epub 2024 
Nov 7.

Plant ribosomes as a score to fathom the melody of 2'-O-methylation across 
evolution.

Neumann SA(1)(2), Gaspin C(3)(4), Sáez-Vásquez J(1)(2).

Author information:
(1)CNRS, Laboratoire Génome et Développement des Plantes (LGDP), UMR 5096, 
Perpignan, France.
(2)University Perpignan Via Domitia, LGDP, UMR 5096, Perpignan, France.
(3)Université Fédérale de Toulouse, INRAE, MIAT, Castanet-Tolosan, France.
(4)Université Fédérale de Toulouse, INRAE, BioinfOmics, Genotoul Bioinformatics 
Facility, Castanet-Tolosan, France.

2'-O-ribose methylation (2'-O-Me) is one of the most common RNA modifications 
detected in ribosomal RNAs (rRNA) from bacteria to eukaryotic cells. 2'-O-Me 
favours a specific RNA conformation and protects RNA from hydrolysis. Moreover, 
rRNA 2'-O-Me might stabilize its interactions with messenger RNA (mRNA), 
transfer RNA (tRNA) or proteins. The extent of rRNA 2'-O-Me fluctuates between 
species from 3-4 sites in bacteria to tens of sites in archaea, yeast, algae, 
plants and human. Depending on the organism as well as the rRNA targeting site 
and position, the 2'-O-Me reaction can be carried out by several site-specific 
RNA methyltransferases (RMTase) or by a single RMTase associated to specific RNA 
guides. Here, we review current progresses in rRNA 2'-O-Me (sites/Nm and 
RMTases) in plants and compare the results with molecular clues from unicellular 
(bacteria, archaea, algae and yeast) as well as multicellular (human and plants) 
organisms.

DOI: 10.1080/15476286.2024.2417152
PMID: 39508203 [Indexed for MEDLINE]


5. Inorg Chem. 2024 Nov 7. doi: 10.1021/acs.inorgchem.4c04050. Online ahead of 
print.

Tuning the Properties of Rigidified Acyclic DEDPA(2-) Derivatives for 
Application in PET Using Copper-64.

Torralba-Maldonado D(1), Marlin A(2), Lucio-Martínez F(3), Freire-García A(3), 
Whetter J(2), Brandariz I(3), Iglesias E(3), Pérez-Lourido P(4), Ortuño RM(1), 
Boros E(2), Illa O(1), Esteban-Gómez D(3), Platas-Iglesias C(3).

Author information:
(1)Departament de Química, Universitat Autònoma de Barcelona, 08193, Cerdanyola 
del Vallès, Spain.
(2)Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 
53706, United States.
(3)Centro Interdisciplinar de Química e Bioloxía (CICA) and Departamento de 
Química, Facultade de Ciencias, Universidade da Coruña, Galicia, 15071 A Coruña, 
Spain.
(4)Departamento de Química Inorgánica, Facultad de Química, Universidade de 
Vigo, As Lagoas, Marcosende, 36310 Pontevedra, Spain.

We present a detailed investigation of the coordination chemistry toward 
[natCu/64Cu]copper of a series of H2DEDPA derivatives (H2DEDPA = 
6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing 
cyclohexyl (H2CHXDEDPA), cyclopentyl (H2CpDEDPA) or cyclobutyl (H2CBuDEDPA) 
spacers. Furthermore, we also developed a strategy that allowed the synthesis of 
a H2CBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl 
ring, which can be used for conjugation to targeting units. The X-ray structures 
of the Cu(II) complexes evidence distorted octahedral coordination around the 
metal ion in all cases. Cyclic voltammetry experiments (0.15 M NaCl) evidence 
quasi-reversible reduction waves associated with the reduction of Cu(II) to 
Cu(I). The complexes show a high thermodynamic stability, with log KCuL values 
of 25.11(1), 22.18(1) and 20.19(1) for the complexes of CHXDEDPA2-, CpDEDPA2- 
and CBuDEDPA2-, respectively (25 °C, 1 M NaCl). Dissociation kinetics 
experiments reveal that both the spontaneous- and proton-assisted pathways 
operate at physiological pH. Quantitative labeling with 64CuCl2 was observed at 
0.1 nmol for CHXDEDPA2- and CpDEDPA2-, 0.025 nmol for CBuDEDPA2- and 1 nmol for 
CBuDEDPA-NHBoc2-, with no significant differences observed at 15, 30, and 60 
min. The radio-complexes are stable in PBS over a period of 24 h.

DOI: 10.1021/acs.inorgchem.4c04050
PMID: 39508185