Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Front Pharmacol. 2024 Oct 21;15:1479441. doi: 10.3389/fphar.2024.1479441. 
eCollection 2024.

Scutellarein ameliorates dextran sulfate sodium-induced ulcerative colitis by 
inhibiting colonic epithelial cell proinflammation and barrier disruption.

Tang Q(#)(1), Jia H(#)(2), Qin X(1), Lu Z(1), Huang W(1), Wang Y(1), Cao Z(1).

Author information:
(1)Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational 
Research, School of Traditional Chinese Pharmacy, China Pharmaceutical 
University, Nanjing, Jiangsu, China.
(2)R&D Center, Shanghai Jahwa United Co., Ltd., Shanghai, China.
(#)Contributed equally

INTRODUCTION: Scutellarein (Scu) is a natural occurring flavonoid found in 
multiple traditional Chinese medicines such as Oroxylum indicum (L.) Kurz and 
Scutellaria baicalensis, with various pharmacological activities including 
anti-inflammation, anti-oxidation and myocardial protection. Here, we 
investigated the therapeutic efficacy of Scu on ulcerative colitis (UC) and the 
underlying mechanism.
METHODS: Efficacy of Scu on UC was evaluated in dextran sulfate sodium (DSS) 
induced colitis mouse model. Inflammation in colonic tissues was assessed by 
myeloperoxidase activity assay and RT-qPCR. Barrier proteins expression was 
examined using immunostaining and Western blot. IL-1β-treated HT-29 cells was 
used for mechanical investigation.
RESULTS: Gavage of Scu significantly decreased the DAI score, improved colon 
shortening, ameliorated the pathological score in DSS-treated mice with better 
efficacy than the positive drug, 5-aminosalicylic acid. Scu also inhibited the 
expression levels of cytokines (Il-1β, Tnf-α, Il-1α, Il-6, and Cxcl1) as well as 
barrier proteins (E-cadherin, Occludin, and ZO-1) in colon tissues of DSS mice. 
In intestinal epithelial HT-29 cells, Scu attenuated the IL-1β-downregulated 
expression levels of E-cadherin, occludin, and ZO-1, while reduced 
IL-1β-upregulated IL-6 and IL-8 mRNA levels. Moreover, Scu inhibited the 
phosphorylation and nuclear translocation of NF-κB and suppression of NF-κB 
phosphorylation abolished IL-1β-disrupted epithelial barrier integrity and 
IL-1β-upregulated proinflammatory mediators expression in HT-29 cells.
CONCLUSION: These data demonstrate that Scu is an efficacious therapeutic agent 
to treat UC. Inhibition of inflammatory responses and maintenance of epithelial 
barrier integrity through NF-κB signaling pathway underlines Scu therapeutic 
effect on UC.

Copyright © 2024 Tang, Jia, Qin, Lu, Huang, Wang and Cao.

DOI: 10.3389/fphar.2024.1479441
PMCID: PMC11536309
PMID: 39502535

Conflict of interest statement: Author HJ was employed by Shanghai Jahwa United 
Co., Ltd. The remaining authors declare that the research was conducted in the 
absence of any commercial or financial relationships that could be construed as 
a potential conflict of interest. The author(s) declared that they were an 
editorial board member of Frontiers, at the time of submission. This had no 
impact on the peer review process and the final decision.


2. Heliyon. 2024 Oct 15;10(20):e39402. doi: 10.1016/j.heliyon.2024.e39402. 
eCollection 2024 Oct 30.

Downregulation of aquaporins and PI3K/AKT and upregulation of PTEN expression 
induced by the flavone scutellarein in human colon cancer cell lines.

Tarawneh N(1), Hamadneh L(1)(2), Alshaer W(3), Al Bawab AQ(1), Bustanji Y(4)(5), 
Abdalla S(6).

Author information:
(1)Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University, Amman, 
11733, Jordan.
(2)Department of Basic Medical Sciences, Al-Balqa Applied University, Al-Salt, 
19117, Jordan.
(3)Cell Therapy Center, The University of Jordan, Jordan.
(4)Department of Basic Medical Sciences, College of Medicine, University of 
Sharjah, Sharjah, United Arab Emirates.
(5)Department of Department of Biopharmaceutics and Clinical Pharmacy, School of 
Pharmacy, The University of Jordan, Amman, 11942, Jordan.
(6)Department of Biological Sciences, School of Science, The University of 
Jordan, Amman, 11942, Jordan.

Scutellarein has an anticancer potential, but the pathway of its action has not 
been elucidated. This study investigated scutellarein efficacy against human 
colorectal cancer (CRC) and explored the possible pathway of its action. MTT 
assay was employed to detect scutellarein effect on HT-29, SW-480, and 
HCT116 cells viability. Scutellarein impact on programmed cell death was studied 
by Annexin V-FITC/PI and its role on migration and invasion was detected by 
wound healing and transwell chambers. Aquaporin (AQP) 1, 3, and 5 expression 
before and after scutellarein treatment was approached by quantitative 
polymerase chain reaction (RT‒qPCR) and immunostaining while Western blotting 
was used to explore scutellarein effect on PI3K/AKT pathway. Scutellarein 
induced apoptosis and necrosis in CRC cells, thus inhibiting proliferation, 
migration, and invasion. Colon cancer cells exhibited positive staining for AQP 
1, 3, and 5 which was downregulated by scutellarein. PI3K/AKT pathway mediating 
cell proliferation and growth was also modulated by scutellarein; phosphatase 
and tensin (PTEN) was upregulated, whereas PI3K, AKT, and p-AKT expressions were 
downregulated, and the downstream mTOR and phosphorylated mTOR were also 
suppressed at the protein level. Data indicated that scutellarein suppressed 
growth, migration as well as invasion of these CRC cells by downregulating the 
expression of AQP 1, 3, and 5 and upregulating PTEN where the latter inhibited 
the genes and the proteins involved in PI3K/AKT pathway. The data indicate that 
scutellarein is a promising therapeutic agent that inhibits growth, migration, 
and invasion of CRC cells by down-regulating the expression of AQP 1, 3, and 5 
and by PTEN up-regulation, thus inhibiting PI3K/AKT. These molecular alterations 
represent potential prognostic biomarkers for the metastasis of colon cancer, 
where the down-regulation of AQPs enhances patient survival.

© 2024 The Authors.

DOI: 10.1016/j.heliyon.2024.e39402
PMCID: PMC11532241
PMID: 39498081

Conflict of interest statement: 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. J Ethnopharmacol. 2024 Oct 26:118999. doi: 10.1016/j.jep.2024.118999. Online 
ahead of print.

Scutellarein inhibits lung cancer growth by inducing cell apoptosis and 
inhibiting glutamine metabolic pathway.

Zhang D(1), Wang Y(1), Yu P(1), Sun J(1), Li J(1), Hu Y(2), Meng X(3), Li J(4), 
Xiang L(5).

Author information:
(1)State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu 
University of Traditional Chinese Medicine, Chengdu 611137, P.R. China.
(2)The School of Preclinical Medicine, Chengdu University, Chengdu 610106, P.R. 
China.
(3)State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu 
University of Traditional Chinese Medicine, Chengdu 611137, P.R. China. 
Electronic address: xlm999@cdutcm.edu.cn.
(4)Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & 
Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of 
Electronic Science and Technology of China, Chengdu 610041, China. Electronic 
address: lijuan74@scszlyy.org.cn.
(5)State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu 
University of Traditional Chinese Medicine, Chengdu 611137, P.R. China. 
Electronic address: xianglydr@cdutcm.edu.cn.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi, a widely used 
Chinese medicinal herb, has shown effectiveness against lung cancer. 
Scutellarein, a key component of Scutellaria baicalensis, also demonstrates 
anticancer properties in lung cancer. However, the underlying mechanisms have 
not yet been clarified.
AIM OF THE STUDY: This study aimed to investigate the effects of scutellarein in 
the treatment of NSCLC and its underlying mechanisms.
METHODS: This study explored the effects of scutellarein on non-small cell lung 
cancer (NSCLC) and its mechanisms. A Lewis lung cancer mouse model was 
established to assess scutellarein's anticancer activity in vivo. Additionally, 
the compound's effects on cell proliferation, colony formation, migration, and 
apoptosis were evaluated in vitro using A549 and H1299 lung cancer cells. 
Metabolomics analysis was conducted to identify changes in cellular metabolism 
due to scutellarein, while molecular docking and western blotting techniques 
were employed to elucidate the molecular mechanisms of its anti-lung cancer 
effects.
RESULTS: Scutellarein significantly inhibited lung cancer xenograft tumor 
growth. In vitro studies showed that scutellarein suppressed migration and 
colony formation in A549 and H1299 cells, induced cell cycle arrest, and 
triggered cell apoptosis. Notably, scutellarein profoundly altered amino acid 
metabolism, particularly affecting glutamine metabolites. It affected key 
glutamine transporters ASCT2 and LAT1, as well as glutaminase GLS1, leading to 
their reduced expression.
CONCLUSION: Scutellarein effectively inhibits lung cancer growth both in vivo 
and in vitro by inducing cell apoptosis and downregulating the glutamine 
metabolic pathway.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.jep.2024.118999
PMID: 39490431

Conflict of interest statement: Declaration of Competing Interest The authors 
declare that they have no conflicts of interest in this article.


4. Microb Cell Fact. 2024 Oct 8;23(1):269. doi: 10.1186/s12934-024-02540-9.

In vitro and in vivo activities of scutellarein, a novel polyphosphate kinase 1 
inhibitor against Acinetobacter baumannii infection.

Song Y(1), Lv H(1)(2), Xu L(2), Liu Z(2), Wang J(2), Fang T(2)(3), Deng X(1)(2), 
Zhou Y(4), Li D(5).

Author information:
(1)Department of Respiratory Medicine, Center for Pathogen Biology and 
Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of 
the Ministry of Education, The First Hospital of Jilin University, Changchun, 
Jilin, 130021, China.
(2)State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic 
Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of 
Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin 
University, Changchun, China.
(3)Jilin Mushuo Breeding Co., Ltd, Changchun, Jilin, 130052, China.
(4)Key Laboratory of Ministry of Education for Conservation and Utilization of 
Special Biological Resources in the Western China, School of Life Sciences, 
Ningxia University, Yinchuan, China.
(5)Department of Respiratory Medicine, Center for Pathogen Biology and 
Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of 
the Ministry of Education, The First Hospital of Jilin University, Changchun, 
Jilin, 130021, China. li_dan@jlu.edu.cn.

BACKGROUND: Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 
(PPK1) has attracted much attention by virtue of its importance in bacterial 
pathogenicity and persistence, as well as its exclusive presence in 
microorganisms. However, only very few drugs have been found to be efficacious 
in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein.
RESULTS: In this study, we identified Scutellarein (Scu), a potent PPK1 
inhibitor that could significantly influence PPK1-regulated motility, biofilm 
formation, and bacterial persistence, which was further validated by the results 
of transcriptome analysis. Mechanistic explorations revealed that Scu achieved 
its enzyme inhibitory activity predominantly through direct engagement with the 
active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae 
was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable 
therapeutic benefits of Scu were also observed in the mouse pneumonia model, 
shown mainly by reduced bacterial colonization, pathological lesions, and 
inflammatory factors.
CONCLUSION: Our results revealed that Scu could attenuate the pathogenicity and 
persistence of A. baumannii by interfering with its important kinase PPK1.

© 2024. The Author(s).

DOI: 10.1186/s12934-024-02540-9
PMCID: PMC11462863
PMID: 39379932 [Indexed for MEDLINE]

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


5. Colloids Surf B Biointerfaces. 2024 Sep 24;245:114269. doi: 
10.1016/j.colsurfb.2024.114269. Online ahead of print.

The effects of plant flavones on the membrane boundary potential and lipid 
packing stress.

Martynyuk VA(1), Efimova SS(1), Malykhina AI(1), Ostroumova OS(2).

Author information:
(1)Institute of Cytology of Russian Academy of Sciences, ikhoretsky 4, Saint 
Petersburg 194064, Russian Federation.
(2)Institute of Cytology of Russian Academy of Sciences, ikhoretsky 4, Saint 
Petersburg 194064, Russian Federation. Electronic address: ostroumova@incras.ru.

Here we have revealed the effects of different plant flavones on the 
physicochemical properties of model lipid membranes. We have demonstrated that 
baicalein increases the boundary potential of membranes composed of 
phosphatidylcholine, while wogonin does not affect it. Other flavones tested 
reduce membrane boundary potential, with this ability increasing among 
scutellarein, chrysin, apigenin, morin, fisetin, and luteolin. Molecular 
dynamics simulations demonstrate connection of alteration in boundary potential 
with the preferential orientation of intrinsic flavone dipole moments in 
membranes. We have also shown that flavones reduce the melting point of 
phosphatidylcholine, and this ability increases in the series of luteolin, 
morin, wogonin, scutellarein, apigenin, baicalein, chrysin, and fisetin. The 
introduction of baicalein, chrysin and fisetin also leads to a significant 
decrease in the sharpness of the lipid phase transition. We have hypothesized 
that the localization of flavones in the glycerol backbone or in the C1-C8 
methylene region of lipid hydrocarbon chains leads to an increase in the area 
per lipid and, as a consequence, to an expansion of the lipid melting peak. 
Replacement of neutral phosphatidylcholine with negatively charged 
phosphatidylserine affects the membrane-modifying activity of flavones which 
given the externalization of phosphatidylserine on the surface of cancer cells 
may be crucial in the flavone anticancer effects.

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

DOI: 10.1016/j.colsurfb.2024.114269
PMID: 39341052

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.