Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Int J Mol Sci. 2023 Nov 6;24(21):16004. doi: 10.3390/ijms242116004.

Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal 
Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress.

Sulistyowati E(1), Huang SE(2)(3), Cheng TL(4)(5)(6), Chao YY(7), Li CY(3), 
Chang CW(2)(3), Lin MX(2)(3), Lin MC(8)(9), Yeh JL(2)(3)(10)(11).

Author information:
(1)Faculty of Medicine, University of Islam Malang, Malang City 65145, 
Indonesia.
(2)Department of Pharmacology, College of Medicine, Kaohsiung Medical 
University, Kaohsiung 807, Taiwan.
(3)Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
University, Kaohsiung 807, Taiwan.
(4)Department of Physiology, College of Medicine, Kaohsiung Medical University, 
Kaohsiung 807, Taiwan.
(5)Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical 
University, Kaohsiung 807, Taiwan.
(6)College of Professional Studies, National Pingtung University of Science and 
Technology, Pingtung 912, Taiwan.
(7)Department of Public Health, College of Health Sciences, Kaohsiung Medical 
University, Kaohsiung 807, Taiwan.
(8)Department of Anesthesiology, Chi Mei Medical Center, Tainan 710, Taiwan.
(9)Department of Medical Laboratory Science and Biotechnology, Chung Hwa 
University of Medical Technology, Tainan 717, Taiwan.
(10)Department of Medical Research, Kaohsiung Medical University Hospital, 
Kaohsiung 807, Taiwan.
(11)Department of Marine Biotechnology and Resources, National Sun Yat-sen 
University, Kaohsiung 804, Taiwan.

Aortic wall inflammation, abnormal oxidative stress and progressive degradation 
of extracellular matrix proteins are the main characteristics of abdominal 
aortic aneurysms (AAAs). The nucleotide-binding oligomerization domain-like 
receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation 
plays a crucial role in aortic damage and disease progression. The first aim of 
this study was to examine the effect of baicalein 
(5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in 
apolipoprotein E-deficient (ApoE-/-) mice. The second aim was to define whether 
baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation 
and inflammation in VSMC culture. For male ApoE-/- mice, a clinically relevant 
AAA model was randomly divided into four groups: saline infusion, baicalein 
intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + 
baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang 
II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, 
preserved elastic structure and density and prevented smooth muscle cell 
contractile protein degradation. Baicalein inhibited rat VSMC proliferation and 
migration following the stimulation of VSMC cultures with Ang II while blocking 
the Ang II-inducible cell cycle progression from G0/G1 to the S phase in the 
synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular 
calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated 
that baicalein inhibited the expression of PCNA and significantly lowered levels 
of phospho-Akt and phospho-ERK, along with an increase in baicalein 
concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that 
baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced 
VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 
were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated 
Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 
2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its 
reactive oxygen species (ROS) production decreased, along with the baicalein 
pretreatment. Our overall results indicate that baicalein could have therapeutic 
potential in preventing aneurysm development.

DOI: 10.3390/ijms242116004
PMCID: PMC10647516
PMID: 37958985 [Indexed for MEDLINE]

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


2. Molecules. 2023 Aug 3;28(15):5861. doi: 10.3390/molecules28155861.

Helichrysum stoechas (L.) Moench Inflorescence Extract for Tomato Disease 
Management.

Sánchez-Hernández E(1), Álvarez-Martínez J(1), González-García V(2), 
Casanova-Gascón J(3), Martín-Gil J(1), Martín-Ramos P(1).

Author information:
(1)Department of Agricultural and Forestry Engineering, ETSIIAA, Universidad de 
Valladolid, Avenida de Madrid 44, 34004 Palencia, Spain.
(2)Department of Agricultural, Forest and Environmental Systems, Agrifood 
Research and Technology Centre of Aragón, Instituto Agroalimentario de 
Aragón-IA2 (CITA-Universidad de Zaragoza), Avda. Montañana 930, 50059 Zaragoza, 
Spain.
(3)Instituto Agroalimentario de Aragón-IA2 (CITA-Universidad de Zaragoza), EPS, 
Universidad de Zaragoza, Carretera de Cuarte s/n, 22071 Huesca, Spain.

Helichrysum stoechas is a singular halophyte that has been shown to have 
anti-inflammatory, antioxidant, and allelopathic properties. In the work 
presented herein, we have characterized its inflorescences hydromethanolic 
extract and assessed its antifungal activity for the pre- and postharvest 
management of tomato crop diseases. Gas chromatography-mass spectrometry 
characterization of the extract showed that 4-ethenyl-1,3-benzenediol, 
2,3-dihydro-benzofuran, quinic acid, 
3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-1-benzopyran-4-one, 
1,6-anhydro-β-D-glucopyranose, catechol, scopoletin, and maltol were the main 
constituents. The co-occurrence of pyranones, benzenediols, and quinic acids as 
phytoconstituents of H. stoechas extract resulted in promising in vitro minimum 
inhibitory concentrations of 500, 375, 500, 187.5, 187.5, and 375 μg·mL-1 
against mycelia of Alternaria alternata, Colletotrichum coccodes, Fusarium 
oxysporum f. sp. lycopersici, Rhizoctonia solani, Sclerotinia sclerotiorum, and 
Verticillium dahliae, respectively. Further, to assess the potential of H. 
stoechas inflorescence extract for postharvest tomato crop protection, ex situ 
tests were conducted against C. coccodes, obtaining high protection at a dose of 
750 μg·mL-1. Taking into consideration that the demonstrated activity is among 
the highest reported to date for plant extracts and comparable to that of the 
synthetic fungicides tested as positive controls, H. stoechas inflorescence 
extract may be put forward as a promising biorational and may deserve further 
testing in field-scale studies.

DOI: 10.3390/molecules28155861
PMCID: PMC10421166
PMID: 37570830 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest. The 
funders had no role in the design of the study; in the collection, analyses, or 
interpretation of data; in the writing of the manuscript; or in the decision to 
publish the results.


3. ChemMedChem. 2022 Jan 5;17(1):e202100588. doi: 10.1002/cmdc.202100588. Epub
2021  Nov 11.

Borcalein: a Carborane-Based Analogue of Baicalein with 
12-Lipoxygenase-Independent Toxicity.

Kuhnert R(1), Kuhnert L(2), Sárosi MB(1), George S(3), Draca D(4), Paskas S(4), 
Hofmann B(3), Steinhilber D(3), Honscha W(2), Mijatović S(4), Maksimović-Ivanić 
D(4), Hey-Hawkins E(1).

Author information:
(1)Institute of Inorganic Chemistry, Faculty of Chemistry and Mineralogy, 
Leipzig University, Johannisallee 29, 04103, Leipzig, Germany.
(2)Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary 
Medicine, Leipzig University, An den Tierkliniken 15, 04103, Leipzig, Germany.
(3)Institute of Pharmaceutical Chemistry, University of Frankfurt, 
Max-von-Laue-Straße 9, 60438, Frankfurt, Germany.
(4)Department of Immunology, Institute for Biological Research "Sinisa 
Stankovic", University of Belgrade, Bul. despota Stefana 142, 11060, Belgrade, 
Serbia.

12-Lipoxygenase is crucial for tumour angiogenesis. 
5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable 
inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an 
improvement of the metabolic stability is necessary to enhance the therapeutic 
efficiency. An emerging approach to enhance metabolic stability of carbon-based 
pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, 
such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. 
Therefore, the unsubstituted phenyl ring of baicalein was replaced by 
meta-carborane, resulting in borcalein, the carborane analogue of baicalein. 
This substitution resulted in a decreased inhibitory activity toward 
12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) 
and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour 
selectivity in comparison to baicalein. Surprisingly, borcalein displays a 
different mechanism of cytotoxicity with increased intracellular production of 
reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide 
(NO).

© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.

DOI: 10.1002/cmdc.202100588
PMCID: PMC9298951
PMID: 34694057 [Indexed for MEDLINE]

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


4. Pharmaceutics. 2021 Sep 19;13(9):1516. doi: 10.3390/pharmaceutics13091516.

Synthesis and Biochemical Evaluation of Baicalein Prodrugs.

Son SH(1), Kang J(1), Ahn M(1), Nam S(1), Jung YW(1)(2), Lee KY(1)(2), Jeon 
YH(1)(2), Byun Y(1)(2), Lee K(1)(2).

Author information:
(1)College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Korea.
(2)Institute of Pharmaceutical Science and Translational Research, Korea 
University, 2511 Sejong-ro, Sejong 30019, Korea.

Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog 
from Scutellaria baicalensis, possesses several pharmacological activities 
including antioxidant, antiproliferative, and anti-inflammatory activities. We 
previously reported that baicalein inhibits the thymic stromal lymphopoietin 
(TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active 
ingredient in the treatment of asthma and atopic dermatitis. However, baicalein 
is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which 
limits its preclinical and clinical use. In this study, we designed, 
synthesized, and evaluated baicalein prodrugs that protect the OH group at the 
7-position of the A ring in baicalein with the amino acid carbamate functional 
group. Comprehensive in vitro and in vivo studies identified compound 2 as a 
baicalein prodrug candidate that improved the plasma exposure of baicalein in 
mouse animal studies. Our results demonstrated that this prodrug approach could 
be further adopted to discover oral baicalein prodrugs.

DOI: 10.3390/pharmaceutics13091516
PMCID: PMC8472512
PMID: 34575592

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


5. J Inflamm Res. 2020 Nov 20;13:945-960. doi: 10.2147/JIR.S276925. eCollection 
2020.

Galangin Inhibits LPS-Induced MMP-9 Expression via Suppressing Protein 
Kinase-Dependent AP-1 and FoxO1 Activation in Rat Brain Astrocytes.

Yang CC(1)(2), Hsiao LD(3), Yang CM(3)(4)(5).

Author information:
(1)Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at 
Tao-Yuan, Kwei-San, Tao-Yuan 33302, Taiwan.
(2)School of Traditional Chinese Medicine, College of Medicine, Chang Gung 
University, Kwei-San, Tao-Yuan 33302, Taiwan.
(3)Department of Pharmacology, College of Medicine, China Medical University, 
Taichung 40402, Taiwan.
(4)Program for Biotch Pharmaceutical Industry, China Medical University, 
Taichung 40402, Taiwan.
(5)Department of Post-Baccalaureate Veterinary Medicine, College of Medical and 
Health Science, Asia University, Wufeng, Taichung 41354, Taiwan.

PURPOSE: Neuroinflammation, characterized by the increased expression of 
inflammatory proteins such as matrix metalloproteinases (MMPs), plays a critical 
role in neurodegenerative disorders. Lipopolysaccharide (LPS) has been shown to 
upregulate MMP-9 expression through the activation of various transcription 
factors, including activator protein 1 (AP-1) and forkhead box protein O1 
(FoxO1). The flavonoid 3,5,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one 
(galangin) has been demonstrated to possess antioxidant and anti-inflammatory 
properties in various types of cells. Here, we investigated the mechanisms 
underlying the inhibitory effect of galangin on LPS-induced MMP-9 expression in 
rat brain astrocytes (RBA-1 cells).
METHODS: Pharmacological inhibitors and siRNAs were employed to explore the 
effects of galangin on LPS-challenged RBA-1 cells. Gelatin zymography, Western 
blotting, real-time PCR, and a luciferase reporter assay were used to detect 
MMP-9 activity, protein expression, mRNA levels, and promoter activity, 
respectively. The protein kinases involved in the LPS-induced MMP-9 expression 
were determined by Western blot. A chromatin immunoprecipitation (ChIP) assay 
was employed to evaluate the activity of c-Jun at the MMP-9 promoter.
RESULTS: Galangin treatment attenuated the LPS-mediated induction of MMP-9 
protein and mRNA expression, as well as the activity at the MMP-9 promoter. In 
addition, galangin exerted its inhibitory effects on MMP-9 expression through 
suppressing the LPS-stimulated activation of proline-rich tyrosine kinase 
(Pyk2), platelet-derived growth factor receptor beta (PDGFRβ), phosphoinositide 
3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), 
and mitogen-activated protein kinases (MAPKs). Pretreatment with galangin 
attenuated the LPS-induced phosphorylation of c-Jun and FoxO1. LPS-induced cell 
migration was also suppressed by galangin pretreatment.
CONCLUSION: Galangin attenuates the LPS-induced inflammatory responses, 
including the induction of MMP-9 expression and cell migration, via inhibiting 
Pyk2/PDGFRβ/PI3K/Akt/mTOR/JNK1/JNK2 and p44/p42 MAPK cascade-dependent AP-1 and 
FoxO1 activities. These results provide new insights into the mechanisms through 
which galangin mitigates LPS-induced inflammatory responses, and suggest novel 
strategies for the management of LPS-related brain diseases.

© 2020 Yang et al.

DOI: 10.2147/JIR.S276925
PMCID: PMC7685391
PMID: 33244253

Conflict of interest statement: The authors report no conflicts of interest in 
this work.