Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Physiol Plant. 2024 Nov-Dec;176(6):e14615. doi: 10.1111/ppl.14615.

Comparative transcriptome analysis highlights resistance regulatory networks of 
maize in response to Exserohilum turcicum infection at the early stage.

Li M(#)(1), Qi X(#)(1), Li D(#)(1), Wu Z(1), Liu M(1), Yang W(1), Zang Z(1), 
Jiang L(1)(2).

Author information:
(1)College of Agriculture, Jilin Agricultural University, Changchun, China.
(2)Crop Science Post-doctoral Station, Jilin Agricultural University, Changchun, 
China.
(#)Contributed equally

Northern corn leaf blight, caused by Exserohilum turcicum (E. turcicum), is one 
of the most destructive diseases in maize, leading to serious yield losses. 
However, the underlying molecular mechanisms of E. turcicum infection response 
in maize remain unclear. In this study, we performed comparative transcriptome 
analysis in resistant maize inbred line J9D207 (R) and susceptible maize inbred 
line PH4CV (S) after infecting with E. turcicum at 0 h, 24 h and 72 h, 
respectively. Compared with 0 h, 9656 (24 h) and 8748 (72 h) differentially 
expressed genes (DEGs) were identified in J9D207, and 7915 (24 h) and 7865 
(72 h) DEGs were identified in PH4CV. Kyoto Encyclopedia of Genes and Genomes 
(KEGG) enrichment analysis showed that alpha-linolenic acid metabolism, 
benzoxazinoid biosynthesis, flavonoid biosynthesis and phenylpropanoid 
biosynthesis might be involved in maize defense reactions. Some DEGs coded for 
transcription factors, such as MYB-related, ERF, NAC, bZIP, bHLH and WRKY 
families, which indicated that they may participate in resistance against E. 
turcicum. In addition, DEGs involved in SA, JA, ABA and ET signaling pathways 
were revealed. Moreover, 75 SOD activity-related genes and 421 POD 
activity-related genes were identified through weighted gene co-expression 
network analysis (WGCNA), respectively. These results provide a novel insight 
into the resistance mechanism of maize in response to E. turcicum inoculation.

© 2024 Scandinavian Plant Physiology Society.

DOI: 10.1111/ppl.14615
PMID: 39508116 [Indexed for MEDLINE]


2. Immunopharmacol Immunotoxicol. 2024 Nov 6:1-11. doi: 
10.1080/08923973.2024.2424293. Online ahead of print.

An integrative lipidomics and transcriptomics study revealing Bavachin and 
Icariin synergistically induce idiosyncratic liver injury.

Li Y(1)(2), Cao B(1), Lin M(1), Xu J(1), Qi S(1), Wang J(3), Xiao X(4), Li G(1), 
Li C(1).

Author information:
(1)National Cancer Center/National Clinical Research Center for Cancer/Cancer 
Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 
Beijing, China.
(2)Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences 
& Peking Union Medical College, Beijing, China.
(3)School of Traditional Chinese Medicine, Capital Medical University, Beijing, 
China.
(4)China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese 
PLA General Hospital, Beijing, China.

Objectives: Reports of traditional Chinese medicine (TCM)-related liver injury 
have increased over recent years; however, identifying susceptibility-related 
components and biomarkers remains challenging due to the heterogeneous nature of 
TCM and idiosyncratic drug-induced liver injury (IDILI). Psoraleae Fructus (PF) 
and Epimedii Folium (EF), commonly found in TCM prescriptions, have been 
implicated in IDILI, but their constituents and underlying mechanisms are poorly 
understood. Methods: In this study, we identified bavachin (Bav) and icariin 
(Ica) as susceptibility components for IDILI in PF and EF using a TNF-α-mediated 
mouse model. Lipidomics and transcriptomics were used to investigate their 
related mechanism. Results: Liver biochemistry and histopathology analyses 
revealed that co-exposure to Bav, Ica, and a non-toxic dose of TNF-α 
prestimulation induced significant liver injury, while Bav and Ica alone did 
not. Lipidomics identified seven differentially abundant metabolites in the 
Bav/Ica/TNF-α group compared to the Ica/TNF-α or Bav/TNF-α groups, mainly 
enriched in alpha-linolenic acid (ALA), arachidonic acid (AA), and linoleic acid 
(LA) metabolic pathways. Additionally, transcriptomics revealed 49 
differentially expressed genes (DEGs) in the Bav/TNF-α vs Bav/Ica/TNF-α and 
Ica/TNF-α vs Bav/Ica/TNF-α groups, primarily associated with the PI3K/AKT/mTOR 
signaling pathway and sphingolipid metabolism. Integrative lipidomics and 
transcriptomics analyses identified significant positive correlations between 
five differential metabolites (DMs) - PC (O-16:0_14:1), PG (22:1_20:3), PI 
(16:0_14:1), PS (18:0_19:2), and TG (17:0_18:2_22:5) - and ten DEGs - Nr0b2, 
Btbd19, Btg2, Fam222a, Fam83f, Gtse1, Anln, Gja4, Srrm4, and Zfp13. Conslusions: 
Collectively, these results suggest that alterations in intracellular metabolism 
and gene expression levels may contribute to the synergistic induction of IDILI 
by the incompatible pair Bav and Ica in the presence of TNF-α.

DOI: 10.1080/08923973.2024.2424293
PMID: 39505304


3. J Nutr. 2024 Nov 4:S0022-3166(24)01124-6. doi: 10.1016/j.tjnut.2024.10.047. 
Online ahead of print.

The novel lipid emulsion Vegaven is well tolerated and elicits distinct 
biological actions compared with a mixed-oil lipid emulsion containing fish 
oil:a parenteral nutrition trial in piglets.

Lucchinetti E(1), Lou PH(2), Chakravarty A(3), Marcolla CS(4), Pauline ML(4), 
Wizzard PR(4), Field CJ(5), Wine E(4), Hersberger M(3), Wales PW(6), Turner 
JM(7), Krämer SD(8), Zaugg M(9).

Author information:
(1)Department of Anesthesiology and Pain Medicine, University of Alberta, 
Edmonton, Canada.
(2)Department of Anesthesiology and Pain Medicine, University of Alberta, 
Edmonton, Canada; Department of Pharmacology, University of Alberta, Edmonton, 
Canada.
(3)Division of Clinical Chemistry and Biochemistry, Children's Research Center, 
University Children's Hospital Zurich, University of Zurich, Zurich, 
Switzerland.
(4)Department of Pediatrics, University of Alberta, Edmonton.
(5)Faculty of Agriculture, Life and Environmental Sciences, University of 
Alberta, Canada.
(6)Department of Surgery, Cincinnati Children's Hospital Medical Center and 
University of Cincinnati, Ohio, USA.
(7)Department of Pediatrics, University of Alberta, Edmonton; Faculty of 
Agriculture, Life and Environmental Sciences, University of Alberta, Canada.
(8)Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
(9)Department of Anesthesiology and Pain Medicine, University of Alberta, 
Edmonton, Canada; Department of Pharmacology, University of Alberta, Edmonton, 
Canada. Electronic address: mzaugg@ualberta.ca.

BACKGROUND: Vegaven is a novel lipid emulsion for parenteral nutrition (PN) 
based on 18-carbon n-3 fatty acids, which elicits liver protection via 
interleukin-10 (IL10) in the murine model of PN.
OBJECTIVE: In a preclinical model of PN in neonatal piglets, Vegaven was tested 
for efficacy and safety and compared with a mixed-oil lipid emulsion containing 
fish-oil (SMOFlipid).
METHODS: 4-5-day-old male piglets were randomly allocated to isocaloric 
isonitrogenous PN for 14 days that varied only by the type of lipid emulsion 
(Vegaven, N=8; SMOFlipid, N=8). Hepatic IL10 tissue concentration served as 
primary outcome. Secondary outcomes were organ weights, bile flow, blood 
analyses, plasma insulin and glucagon concentrations, insulin signaling, 
proinflammatory cytokines, tissue lipopolysaccharide concentrations, and fatty 
acid composition of phospholipid fractions in plasma, liver, and brain.
RESULTS: Total weight gain on trial, organ weights, and bile flow were similar 
between the Vegaven and the SMOFlipid group. Vegaven elicited higher hepatic 
IL10 (Δ=148 pg/mg protein, p<0.001) and insulin receptor substrate-2 levels 
(Δ=0.08 O.D., p=0.012). Plasma insulin concentrations (Δ=1.46 mU/L, p=0.003) and 
fructosamine (glycated albumin, Δ=12.4 μmol/g protein, p=0.003) were increased 
in SMOFlipid as compared with Vegaven group, indicating insulin resistance. 
Higher hepatic injury markers were observed more frequently in the SMOFlipid 
group compared with the Vegaven group. Lipopolysaccharide, tumor necrosis 
factor-alpha, and interleukin-6 were increased in pancreatic and brain tissues 
of SMOFlipid- vs Vegaven-treated piglets. Insulin signaling was reduced in the 
brains of SMOFlipid-treated piglets. Vegaven and SMOFlipid elicited distinct 
fatty acid profiles in the phospholipid fractions of the rapidly growing brains, 
but showed similar accretion of docosahexaenoic acid and arachidonic acid after 
two weeks of PN.
CONCLUSIONS: Vegaven was well tolerated in this piglet model of PN and 
demonstrated distinct biological actions compared with SMOFlipid, namely lower 
liver, pancreas, and brain inflammation, enhanced insulin signaling, and 
improved whole-body glucose control.

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.tjnut.2024.10.047
PMID: 39505265

Conflict of interest statement: Declaration of Competing Interest A patent 
application related to the novel lipid emulsion has been submitted to the 
European Patent Office (EP 21/204659.3).


4. Theriogenology. 2024 Nov 1;232:9-19. doi:
10.1016/j.theriogenology.2024.10.026.  Online ahead of print.

α-Linolenic acid promotes testosterone synthesis by improving mitochondrial 
function in primary rooster Leydig cells.

Chang X(1), Li D(1), Guo Y(1), Sheng X(1), Wang X(1), Xing K(1), Xiao L(1), Lv 
X(2), Long C(3), Qi X(4).

Author information:
(1)Animal Science and Technology College, Beijing University of Agriculture, 
Beijing, 102206, China.
(2)Department of Livestock and Poultry Products Testing, Beijing General Station 
of Animal Husbandry, Beijing, 100107, China.
(3)Animal Science and Technology College, Beijing University of Agriculture, 
Beijing, 102206, China. Electronic address: cheng.long@bua.edu.cn.
(4)Animal Science and Technology College, Beijing University of Agriculture, 
Beijing, 102206, China. Electronic address: buaqxl@126.com.

The present study aimed to investigate the direct effects of α-Linolenic acid 
(ALA) on the in vitro production of testosterone and the expression of key 
enzymes and proteins related to steroidogenesis in Leydig cells of roosters.
METHODS: Purified primary Leydig cells isolated from 65-week-old roosters were 
purified and treated with different concentrations of ALA treatments: (0 μm/L 
[control], solvent control group (DMSO), 20 μM/L, 40 μM/L, and 80 μM/L) and cell 
counting-8 (CCK-8) for cell viability assay, Enzyme-linked immunosorbent assay 
(ELISA) kit for the determination of testosterone in cell supernatants, 
quantitative (real-time) PCR, and analysis of activities of antioxidants 
catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA), evaluation 
of mitochondrial membrane potential, pro- and anti-apoptotic proteins/genes 
Bcl-2, Bcl-2-associated X protein (Bax), apoptosis-inducing factor (AIF) were 
done respectively.
RESULTS: Our results showed that ALA significantly increased testosterone 
secretion in primary rooster Leydig cells (P < 0.05), and 40 μM/L is the optimal 
dose. Leydig cells supplemented with ALA (20, 40, 80 μM) increased the 
expression of key enzymes and proteins 3β-hydroxysteroid dehydrogenase (3β-HSD), 
steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage 
enzyme (P450scc) concerning steroidogenesis, enhanced antioxidant capability, 
improved mitochondrial biogenesis, and markedly improved the mitochondrial 
membrane potential (P < 0.05). Furthermore, the expression of the 
apoptosis-suppressive gene Bcl-2 was significantly increased, but Bax and AIF 
expression was decreased in the ALA group compared to that in the control group 
(P < 0.05).
CONCLUSION: ALA promoted testosterone production, enhanced steroidogenic enzyme 
expression, improved mitochondrial function, and antioxidant capacity, and 
reduced apoptosis in primary rooster Leydig cells, with 40 μM/L identified as 
the optimal concentration.

Copyright © 2024 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.theriogenology.2024.10.026
PMID: 39504870

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


5. Mol Pharm. 2024 Nov 4. doi: 10.1021/acs.molpharmaceut.4c00190. Online ahead of
 print.

Methyl-β-cyclodextrin Enhances Tumor Cellular Uptake and Accumulation of 
α-Linolenic Acid-Paclitaxel Conjugate Nanoparticles.

Xu M(1)(2), Liu J(1), Yu J(1), Wang J(1), Li H(1), Zhong T(1), Hao Y(1), Li 
Z(1), Wang J(1), Huang X(1), Wang H(1), Tian Y(1), Zhao H(1), Wei Q(1), Zhang 
X(1)(3).

Author information:
(1)Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking 
University, Beijing 100191, China.
(2)Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang 
Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China.
(3)Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery 
Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, 
China.

Improving nanomedicine uptake by tumor cells is key to achieving intracellular 
drug delivery. In this study, we found that methyl-β-cyclodextrin (MβCD) can 
significantly promote the intracellular accumulation of nanoparticulated 
α-linolenic acid-paclitaxel conjugates (ALA-PTX NPs) via enhanced 
clathrin-mediated endocytosis and limited degradation in lysosomes. Our in vitro 
results indicated that MβCD not only reduced the plasma membrane cholesterol 
content and increased plasma membrane fluidity, leading to ALA-PTX NPs being 
more easily incorporated into the plasma membrane, further enhancing membrane 
fluidity and making the plasma membrane more susceptible to tensile deformation, 
forming intracellular vesicles to enhance ALA-PTX NP cellular uptake, but also 
destroyed lysosomes and then limited ALA-PTX NPs' degradation in lysosomes. In 
HepG2 tumor-bearing mice, MβCD was also able to enhance the antitumor activity 
of ALA-PTX NPs in vivo. Moreover, we found that MβCD specifically promoted 
PUFA-paclitaxel conjugate NP cellular uptake. The cellular uptake of PTX 
liposome which shares an endocytosis pathway with ALA-PTX NPs could be enhanced 
by MβCD combined with ALA or ALA-PTX NPs. Therefore, we suggested that MβCD 
combined with polyunsaturated fatty acid-conjugation would be an effective 
strategy for improving intracellular delivery of nanoparticulated 
chemotherapeutic drugs used for combination administration to enhance antitumor 
efficiency.

DOI: 10.1021/acs.molpharmaceut.4c00190
PMID: 39495317