Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Med Chem. 2024 Feb 22;67(4):2802-2811. doi: 10.1021/acs.jmedchem.3c01943.
Epub  2024 Feb 8.

Chelerythrine Chloride is an Affinity-Labeling Inactivator of CYP3A4 by 
Modification of Cysteine239.

Mao X(1)(2), Zhao G(3), Wang Q(3)(4), He J(1), Liu Y(1), Liu T(1), Li W(1), Peng 
Y(3), Zheng J(1)(3).

Author information:
(1)State Key Laboratory of Functions and Applications of Medicinal Plants, 
Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, 
Guiyang 550004, Guizhou, PR China.
(2)Department of Pharmaceutical Analysis, College of Pharmacy, Mudanjiang 
Medical University, Mudanjiang 157011, PR China.
(3)Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 
110016, Liaoning, PR China.
(4)Shuangyashan Disease Control and Prevention Center, Shuangyashan 155100, PR 
China.

Chelerythrine chloride (CHE) is a quaternary benzo[c]phenanthridine alkaloid 
with an iminium group that was found to cause time- and concentration-dependent 
inhibition of CYP3A4. The loss of CYP3A4 activity was independent of NADPH. 
CYP3A4 competitive inhibitor ketoconazole and nucleophile N-acetylcysteine (NAC) 
slowed the inactivation. No recovery of CYP3A4 activity was observed after 
dialysis. Dihydrochelerythrine hardly inhibited CYP3A4, suggesting that the 
iminium group was primarily responsible for the inactivation. UV spectral 
analysis revealed that the maximal absorbance of CHE produced a significant 
red-shift after being mixed with NAC, suggesting that 1,2-addition possibly took 
place between the sulfhydryl group of NAC and iminium group of CHE. Molecular 
dynamics simulation and site-direct mutagenesis studies demonstrated that 
modification of Cys239 by the iminium group of CHE attributed to the 
inactivation. In conclusion, CHE is an affinity-labeling inactivator of CYP3A4. 
The observed enzyme inactivation resulted from the modification of Cys239 of 
CYP3A4 by the iminium group of CHE.

DOI: 10.1021/acs.jmedchem.3c01943
PMID: 38330258 [Indexed for MEDLINE]


2. J Med Chem. 2022 Dec 8;65(23):15738-15748. doi: 10.1021/acs.jmedchem.2c01262. 
Epub 2022 Nov 21.

Riboflavin-Promoted In Situ Photoactivation of Dihydroalkaloid Prodrugs for 
Cancer Therapy.

Yang X(1), Ma L(2), Shao H(2), Zhou Z(1), Ling X(1), Yao M(2), Luo G(2), 
Scoditti S(3), Sicilia E(3), Mazzone G(3), Gao M(1), Tang BZ(4).

Author information:
(1)National Engineering Research Center for Tissue Restoration and 
Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, 
Key Laboratory of Biomedical Materials and Engineering of the Ministry of 
Education, Innovation Center for Tissue Restoration and Reconstruction, South 
China University of Technology, Guangzhou 510006, China.
(2)Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong 
Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
(3)Department of Chemistry and Chemical Technologies, Università della Calabria, 
87036 Arcavacata di Rende, Cosenza, Italy.
(4)Shenzhen Institute of Aggregate Science and Technology, School of Science and 
Engineering, The Chinese University of Hong Kong, 2001 Longxiang Boulevard, 
Longgang, Shenzhen, Guangdong 518172, China.

Cancer therapies usually suffer from poor targeting ability and serious side 
effects. Photoactivatable cancer therapy has the significant advantage of a high 
spatiotemporal resolution, but most photoactivatable prodrugs require decoration 
with stoichiometric photocleavable groups, which are only responsive to 
ultraviolet irradiation and suffer from low reaction efficiency. To tackle these 
challenges, we herein propose a photoactivation strategy with biogenic 
riboflavin as the photosensitizer to promote the in situ transformation of 
noncytotoxic dihydroalkaloid prodrugs dihydrochelerythrine (DHCHE), 
dihydrosanguinarine (DHSAN), and dihydronitidine (DHNIT) into anticancer 
alkaloid drugs chelerythrine (CHE), sanguinarine (SAN), and nitidine (NIT), 
respectively, which can efficiently kill cancer cells and inhibit in vivo tumor 
growth. Meanwhile, the photoactivatable transformation can be in situ monitored 
by green-to-red fluorescence conversion, which will contribute to easy 
controlling of the therapeutic dose. The proposed photoactivatable 
transformation mechanism was also explored by density functional theory (DFT) 
calculations. We believe this riboflavin-promoted and imaging-guided 
photoactivation strategy is promising for precise cancer therapy.

DOI: 10.1021/acs.jmedchem.2c01262
PMID: 36410876 [Indexed for MEDLINE]


3. Evid Based Complement Alternat Med. 2022 Sep 19;2022:2322417. doi: 
10.1155/2022/2322417. eCollection 2022.

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an 
Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell 
Experiments.

Zeng L(1), Lin Z(1)(2), Kang P(1)(3)(4), Zhang M(5), Tang H(1)(3), Li 
M(1)(3)(4), Xu K(6), Liu Y(1)(2), Jiang Z(7), Huo S(7).

Author information:
(1)Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
(2)College of Basic Medicine, Guangzhou University of Chinese Medicine, 
Guangzhou 510006, China.
(3)Department of Joint Orthopaedic, The First Affiliated Hospital of Guangzhou 
University of Chinese Medicine, Guangzhou 510405, China.
(4)Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, 
Guangzhou 510405, China.
(5)Department of Orthopedics, Henan Provincial People's Hospital, People's 
Hospital of Zhengzhou University, People's Hospital of Henan University, 
Zhengzhou 450003, China.
(6)Shi's Center of Orthopedics and Traumatology, Shuguang Hospital, Affiliated 
to Shanghai University of Traditional Chinese Medicine, Institute of 
Traumatology & Orthopedics, Shanghai Academy of Traditional Chinese Medicine, 
Shanghai, China.
(7)Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, 
Shenzhen 518048, China.

BACKGROUND: This study aimed to investigate the molecular mechanism of 
Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty 
arthritis (GA) and interleukin-1-beta (IL-1β) inhibitors by using network 
pharmacology, molecular docking, and cell experiments.
METHODS: In this study, the compounds of TFDC and the potential inflammatory 
targets of GA were obtained from Traditional Chinese Medicine Systems 
Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian 
Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential 
targets interaction network was accomplished by the STRING database. The 
TFDC-active compound-potential target-GA network was constructed using Cytoscape 
software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) 
pathway enrichment analyses were used to further explore the GA mechanism and 
therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to 
verify whether the TFDC inhibited IL-1β in GA. Molecular docking technology was 
used to analyze the optimal effective compounds from the TFDC for docking with 
IL-1β.
RESULT: 133 active compounds and 242 targets were screened from the TFDC, and 25 
of the targets intersected with GA inflammatory targets, which were considered 
as potential therapeutic targets. Network pharmacological analysis showed that 
the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, 
rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had 
better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, 
SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory 
signaling pathways of the active compounds for treating GA are IL-17 signaling 
pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B 
signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling 
pathway, etc. The TFDC reduced IL-1β mRNA expression in GA by qPCR. Molecular 
docking results suggested that rutaecarpine was the most appropriate natural 
IL-1β inhibitor.
CONCLUSION: Our findings provide an essential role and bases for further 
immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1β 
inhibitors development in GA.

Copyright © 2022 Liying Zeng et al.

DOI: 10.1155/2022/2322417
PMCID: PMC9526673
PMID: 36193152

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as potential conflicts of interest.


4. Phytochemistry. 2022 Oct;202:113321. doi: 10.1016/j.phytochem.2022.113321.
Epub  2022 Jul 31.

Isoquinoline alkaloids from Hylomecon japonica and their potential anti-breast 
cancer activities.

Cao Z(1), Zhu S(1), Xue Z(1), Zhang F(1), Zhang L(1), Zhang Y(1), Guo Y(1), Zhan 
G(1), Zhang X(2), Guo Z(3).

Author information:
(1)School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China.
(2)School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China. 
Electronic address: zhangxinxin360@126.com.
(3)School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, PR China. 
Electronic address: guozj@xjtu.edu.cn.

Four pairs of undescribed enantiomeric isoquinoline alkaloids 
(6S/R-(N,N-diethylacetamido)yl-dihydrochelerythrine, 
6R/S-acetonyl-9-hydroxy-dihydrochelerythrine, 
6S/R-acroleinyl-dihydrochelerythrine, 6S/R-acetatemethyl-dihydrochelerythrine), 
five undescribed isoquinoline alkaloids (6,10-dimethoxydihydrochelerythrine, 
6-ethoxy-ethaniminyl-dihydrochelandine, 9-hydroxy-dihydrochelerythrine, 
9-methoxy-10-hydroxy-norchelerythrine, chelidoniumine A), together with 13 known 
isoquinoline alkaloids were isolated from an extract of the roots and rhizomes 
of Hylomecon japonica. The structures of the undescribed compounds were 
identified by NMR, HRESIMS, UV, IR, and their absolute configurations were 
defined via electronic circular dichroism data and optical rotation. All of the 
isolated compounds were tested for their anti-breast cancer activities in 
MCF-7 cells. Among them, the undescribed alkaloids 
6S/R-acroleinyl-dihydrochelerythrine, 6,10-dimethoxydihydrochelerythrine, 
6-ethoxy-ethaniminyl-dihydrochelandine, 9-methoxy-10-hydroxy-norchelerythrine 
and other known alkaloids 6-methoxydihydrosanguinarine, 
6-acetaldehyde-dihyrochelerythrine, dihydrosanguinaline and 10-methoxy 
boconoline had good inhibitory effects on MCF-7 cells of breast cancer with an 
IC50 lower than 20 μM.

Copyright © 2022. Published by Elsevier Ltd.

DOI: 10.1016/j.phytochem.2022.113321
PMID: 35921889 [Indexed for MEDLINE]


5. Molecules. 2022 Jul 22;27(15):4693. doi: 10.3390/molecules27154693.

Fluorescence, Absorption, Chromatography and Structural Transformation of 
Chelerythrine and Ethoxychelerythrine in Protic Solvents: A Comparative Study.

Cao J(1), Zheng Y(2), Liu T(1), Liu J(1), Liu J(1), Wang J(3), Sun Q(3), Li 
W(1), Wei Y(3).

Author information:
(1)Department of Environmental and Chemical Engineering, Hebei College of 
Industry and Technology, Shijiazhuang 050091, China.
(2)Department of Preschool and Arts Education, Shijiazhuang Vocational College 
of Finance & Economics, Shijiazhuang 050061, China.
(3)College of Chemistry and Material Science, Hebei Normal University, 
Shijiazhuang 050024, China.

Chelerythrine (CH) and ethoxychelerythrine (ECH) are chemical reference 
substances for quality control of Chinese herbal medicines, and ECH is the 
dihydrogen derivative of CH. In this study, their fluorescence and absorption 
spectra, as well as their structural changes in different protic solvents were 
compared. It was observed that their emission fluorescence spectra in methanol 
were almost the same (both emitted at 400 nm), which may be attributed to the 
nucleophilic and exchange reactions of CH and ECH with methanol molecules with 
the common product of 6-methoxy-5,6-dihydrochelerythrine (MCH). When diluted 
with water, MCH was converted into CH, which mainly existed in the form of 
positively charged CH+ under acidic and near-neutral conditions with the 
fluorescence emission at 550 nm. With the increase of pH value of the aqueous 
solution, CH+ converted to 6-hydroxy-5,6-dihydrochelerythrine (CHOH) with the 
fluorescence emission at 410 nm. The fluorescence quantum yields of MCH and CHOH 
were 0.13 and 0.15, respectively, and both the fluorescence intensities were 
much stronger than that of CH+. It is concluded that CH and ECH can substitute 
each other in the same protic solvent, which was further verified by 
high-performance liquid chromatography. This study will help in the 
investigation of structural changes of benzophenanthridine alkaloids and will 
provide the possibility for the mutual substitution of standard substances in 
relevant drug testing.

DOI: 10.3390/molecules27154693
PMCID: PMC9331999
PMID: 35897862 [Indexed for MEDLINE]

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