Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Front Microbiol. 2024 Oct 15;15:1400616. doi: 10.3389/fmicb.2024.1400616. 
eCollection 2024.

Understory growth of Paris polyphylla accumulates a reservoir of secondary 
metabolites of plants.

Yan X(#)(1), Wang D(#)(1)(2), Zhang A(#)(1), Xia J(1), Jiao J(1), Ghanim M(3), 
Xiaokun O(2), He X(1), Shi R(1)(2).

Author information:
(1)Key Laboratory for Forest Resources Conservation and Utilization in the 
Southwest Mountains of China, Ministry of Education, International Ecological 
Forestry Research Center of Kunming, Southwest Forestry University, Yunnan, 
Kunming, China.
(2)Ministry of Education Key Laboratory for Microbial Resources, Yunnan 
University, Kunming, Yunnan, China.
(3)Department of Entomology, Institute of Plant Protection, Rishon LeZion, 
Israel.
(#)Contributed equally

Paris polyphylla is an important traditional medicinal plant of the Himalayan 
region. It is extensively used for the production of natural steroidal saponins 
and flavonoids. Although seed dormancy of wild plants can be broken to be 
artificially maintained and regenerated through micropropagation in the 
laboratory, the success of secondary metabolite production in higher quantities 
and the synthesis of superior plant metabolites have been very limited. In this 
study, we present differential metabolic profiling of P. polyphylla plants 
maintained for 8 years in natural and greenhouse conditions. Untargeted 
profiling of the metabolites through ultra-performance liquid 
chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), followed by 
statistical analysis, identified secondary metabolites that were enriched in the 
naturally occurring plant roots compared with the greenhouse plant roots. A 
multivariate statistical analysis revealed the differential distribution of the 
compounds between the two groups. Overall, we identified 1,182 secondary 
metabolites, with 116 metabolites being differentially upregulated and 256 
metabolites being downregulated. Moreover, 810 metabolites showed no significant 
variation under both growing conditions. The Kyoto Encyclopedia of Genes and 
Genomes (KEGG) analysis revealed that the naturally forest-grown P. polyphylla 
plants were significantly enriched in steroidal saponins, lipids, vitamins, 
flavonoids, and flavonols. An analysis of the top 10 differentially upregulated 
secondary metabolites indicated a significantly enriched quantity of 
spirost-5-en-3,12-diol and kaempferol synthesis pathways, which are known to 
reduce the effect of free radicals scavengers inside the cell. In addition, 
veratramine alkaloids were also enriched under natural conditions. Our findings 
indicated that naturally maintained P. polyphylla plants are suitable for the 
extraction of medicinally important compounds. Our study established a causal 
relationship between the metabolic composition of the roots and their natural 
growth condition. This study highlighted the importance of environmental 
conditions in the biosynthesis of secondary metabolites of plants.

Copyright © 2024 Yan, Wang, Zhang, Xia, Jiao, Ghanim, Xiaokun, He and Shi.

DOI: 10.3389/fmicb.2024.1400616
PMCID: PMC11518744
PMID: 39473849

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 a potential conflict of interest.


2. Plant Physiol Biochem. 2024 Nov;216:109087. doi: 10.1016/j.plaphy.2024.109087.
 Epub 2024 Sep 2.

Integration of induction, system optimization and genetic transformation in 
Veratrum californicum var. vitro cultures to enhance the production of 
cyclopamine and veratramine.

Zuo A(1), He D(2), Sun C(1), Wen Y(1), Li H(1), Kou C(3), Shao G(4), Xue Z(3), 
Ma R(5), Wei J(5), Liu J(1), Ma P(6).

Author information:
(1)College of Life Sciences, Northwest A&F University, Yangling, 712100, China.
(2)College of Life Sciences, Northwest A&F University, Yangling, 712100, China. 
Electronic address: hedi1743408942@163.com.
(3)Heilongjiang Key Laboratory of Plant Bioactive Substance Biosynthesis and 
Utilization, Northeast Forestry University, Harbin, 150040, China.
(4)Xian Agricultural Technology Extension Center, Xian, China.
(5)Jilin Provincial Key Laboratory of Agricultural Biotechnology, Jilin Academy 
of Agricultural Sciences, Changchun, 130033, China.
(6)College of Life Sciences, Northwest A&F University, Yangling, 712100, China. 
Electronic address: mapengda@163.com.

Cyclopamine, a compound found in wild Veratrum has shown promising potential as 
a lead anti-cancer drug by effectively blocking cancer signaling pathways. 
However, its complex chemical structure poses challenges for artificial 
synthesis, thus limiting its supply and downstream drug production. This study 
comprehensively utilizes induction, system optimization, and transgenic 
technologies to establish an efficient suspension culture system for the 
high-yield production of cyclopamine and its precursor, veratramine. 
Experimental results demonstrate that methyl jasmonate (MeJA) effectively 
promotes the content of veratramine and cyclopamine in Veratrum californicum 
var. callus tissue, while yeast extract (YE) addition significantly increases 
cell biomass. The total content of veratramine and cyclopamine reached 0.0638 mg 
after synergistic treatment of suspension system with these two elicitors. And 
the content of the two substances was further increased to 0.0827 mg after the 
optimization by response surface methodology. Subsequently, a genetic 
transformation system for V. californicum callus was established and a crucial 
enzyme gene VnOSC1, involved in the steroidal alkaloid biosynthesis pathway, was 
screened and identified for genetic transformation. Combined suspension culture 
and synergistic induction system, the total content of the two substances in 
transgenic suspension system was further increased to 0.1228 mg, representing a 
276.69% improvement compared to the initial culture system. This study proposes 
a complete and effective genetic transformation and cultivation scheme for V. 
californicum tissue cells, achieving milligram-level production of the 
anticancer agent cyclopamine and its direct precursor veratramine for the first 
time. It provides a theoretical basis for the industrial-scale production of 
these substances.

Copyright © 2024 Elsevier Masson SAS. All rights reserved.

DOI: 10.1016/j.plaphy.2024.109087
PMID: 39241631 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare no conflicts of interest.


3. Nat Commun. 2024 Sep 2;15(1):7639. doi: 10.1038/s41467-024-52134-7.

Divergent syntheses of complex Veratrum alkaloids.

Guo Y(#)(1), Fang R(#)(2), Jiao Y(#)(1), Liu J(1), Lu JT(1), Luo T(3)(4)(5).

Author information:
(1)Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry 
of Education, Beijing National Laboratory for Molecular Science, College of 
Chemistry and Molecular Engineering, Peking University, Beijing, China.
(2)Peking-Tsinghua Center for Life Sciences, Academy for Advanced 
Interdisciplinary Studies, Peking University, Beijing, China.
(3)Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry 
of Education, Beijing National Laboratory for Molecular Science, College of 
Chemistry and Molecular Engineering, Peking University, Beijing, China. 
tuopingluo@pku.edu.cn.
(4)Peking-Tsinghua Center for Life Sciences, Academy for Advanced 
Interdisciplinary Studies, Peking University, Beijing, China. 
tuopingluo@pku.edu.cn.
(5)Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, 
Guangdong, China. tuopingluo@pku.edu.cn.
(#)Contributed equally

The Veratrum alkaloids are a class of highly intricate natural products renowned 
for their complex structural and stereochemical characteristics, which underlie 
a diverse array of pharmacological activities ranging from anti-hypertensive 
properties to antimicrobial effects. These properties have generated substantial 
interest among both synthetic chemists and biologists. While numerous 
advancements have been made in the synthesis of jervanine and veratramine 
subtypes over the past 50 years, the total synthesis of highly oxidized cevanine 
subtypes has remained relatively scarce. Building on the efficiency of our 
previously developed strategy for constructing the hexacyclic carbon skeleton of 
the Veratrum alkaloid family via a stereoselective intramolecular Diels-Alder 
reaction and radical cyclization, here we show the development of a unified 
synthetic approach to access highly oxidized Veratrum alkaloids. This includes 
the total synthesis of (-)-zygadenine, (-)-germine, (-)-protoverine and the 
alkamine of veramadine A, by capitalizing on a meticulously designed sequence of 
redox manipulations and a late-stage neighboring-group participation strategy.

© 2024. The Author(s).

DOI: 10.1038/s41467-024-52134-7
PMCID: PMC11369162
PMID: 39223144 [Indexed for MEDLINE]

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


4. Nat Commun. 2024 Jun 22;15(1):5332. doi: 10.1038/s41467-024-49748-2.

Divergent and gram-scale syntheses of (-)-veratramine and (-)-cyclopamine.

Hou W(1), Lin H(1), Wu Y(1), Li C(1), Chen J(1), Liu XY(2), Qin Y(3).

Author information:
(1)Key Laboratory of Drug-Targeting and Drug Delivery System of the Education 
Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced 
Drug and Sichuan Research Center for Drug Precision Industrial Technology, West 
China School of Pharmacy, Sichuan University, Chengdu, China.
(2)Key Laboratory of Drug-Targeting and Drug Delivery System of the Education 
Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced 
Drug and Sichuan Research Center for Drug Precision Industrial Technology, West 
China School of Pharmacy, Sichuan University, Chengdu, China. xyliu@scu.edu.cn.
(3)Key Laboratory of Drug-Targeting and Drug Delivery System of the Education 
Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced 
Drug and Sichuan Research Center for Drug Precision Industrial Technology, West 
China School of Pharmacy, Sichuan University, Chengdu, China. 
yongqin@scu.edu.cn.

Veratramine and cyclopamine, two of the most representative members of the 
isosteroidal alkaloids, are valuable molecules in agricultural and medicinal 
chemistry. While plant extraction of these compounds suffers from uncertain 
supply, efficient chemical synthesis approaches are in high demand. Here, we 
present concise, divergent, and scalable syntheses of veratramine and 
cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive 
dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both 
target natural products by utilizing a biomimetic rearrangement to form the 
C-nor-D-homo steroid core and a stereoselective reductive 
coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.

© 2024. The Author(s).

DOI: 10.1038/s41467-024-49748-2
PMCID: PMC11193734
PMID: 38909052 [Indexed for MEDLINE]

Conflict of interest statement: Y.Q., X.Y.L., and W.H. are listed as inventors 
on patents ‘Synthesis of veratramine’ (CN2023118206686) and ‘Synthesis of 
cyclopamine’(CN2024103595370) filed by Sichuan University on some aspects of the 
work in this paper. The other authors declare no competing interests.


5. Phytochem Anal. 2024 Oct;35(7):1577-1586. doi: 10.1002/pca.3401. Epub 2024 Jun
 11.

Determination of Veratrum alkaloid contents in three Veratrum species by 
HPLC-MS/MS.

Siegle J(1), Pietsch J(1).

Author information:
(1)Institute of Legal Medicine, Medical Faculty Carl Gustav Carus, Technical 
University Dresden, Fetscherstraße 74, Dresden, D-01307, Germany.

INTRODUCTION: Veratrum alkaloids have gained attention due to their toxic 
effects and potential pharmaceutical applications, particularly in cancer and 
cardiology. Over 200 alkaloids are found in species of the Veratrum genus. The 
alkaloid composition and concentrations can greatly vary in plants depending on 
factors like species, plant part, location, season, weather, or nutrients.
OBJECTIVE: This study aims an analytical approach to analyze and quantify 
Veratrum alkaloids in different plant parts of Veratrum species. The purpose is 
to contribute essential alkaloid concentration data for future research on the 
pharmacological and toxicological aspects of Veratrum alkaloids.
METHODS: This study focuses on five Veratrum alkaloids (cevadine, jervine, 
protoveratrine A, veratramine, and veratridine) in three Veratrum species 
(Veratrum album L., Veratrum californicum Durand, and Veratrum nigrum L.) 
collected from four German botanical gardens (Dresden, Leipzig, Marburg, and 
Schellerhau). A liquid-liquid extraction method and a sensitive high-performance 
liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method 
operating in multiple reaction monitoring (MRM) mode were applied for the 
alkaloid determination.
RESULTS: Quantification revealed varying alkaloid concentrations among plant 
parts and Veratrum species in the μg/g to mg/g range. Protoveratrine A exhibited 
the highest content, while veratramine concentrations were generally lower. 
Especially in fruit, roots and rootstock of Veratrum album L. alkaloid 
concentrations were significant high.
CONCLUSION: The developed HPLC-MS/MS method successfully determined Veratrum 
alkaloid concentrations in plant samples. The study contributes valuable data on 
Veratrum alkaloid distribution in different species and plant parts, crucial for 
understanding their potential medicinal and toxicological significance.

© 2024 The Author(s). Phytochemical Analysis published by John Wiley & Sons Ltd.

DOI: 10.1002/pca.3401
PMID: 38863228 [Indexed for MEDLINE]