Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Planta. 2023 Dec 27;259(2):30. doi: 10.1007/s00425-023-04311-z.

Modulation of terpenoid indole alkaloid pathway via elicitation with 
phytosynthesized silver nanoparticles for the enhancement of ajmalicine, a 
pharmaceutically important alkaloid.

Verma SK(1)(2), Goyary D(3), Singh AK(2), Anandhan S(4), Raina SN(5), Pandey 
S(6), Kumar S(7), Khare N(8).

Author information:
(1)Nims Institute of Allied Medical Science and Technology, Nims University 
Rajasthan, Delhi-Jaipur Highway, NH-11C, Jaipur, 303121, Rajasthan, India.
(2)National Bureau of Plant Genetic Resources, Pusa Campus, New Delhi, 110012, 
India.
(3)Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, 
Assam, India.
(4)ICAR-Directorate of Onion and Garlic Research, Rajgurunagar, Pune, 410505, 
Maharashtra, India.
(5)Amity Institute of Biotechnology, Amity University Uttar Pradesh, Uttar 
Pradesh, Sector 125, Noida, 201313, India.
(6)School of Bioengineering and Food Technology, Faculty of Applied Sciences and 
Biotechnology, Shoolini University, Solan, 173229, Himachal Pradesh, India.
(7)National Centre for Cell Science, Ganeshkhind, Pune, 411007, Maharashtra, 
India.
(8)Nims Institute of Allied Medical Science and Technology, Nims University 
Rajasthan, Delhi-Jaipur Highway, NH-11C, Jaipur, 303121, Rajasthan, India. 
neerajsnkhare@gmail.com.

The use of silver nanoparticles as elicitors in cell cultures of Rauwolfia 
serpentina resulted in increased levels of ajmalicine, upregulated structural 
and regulatory genes, elevated MDA content, and reduced activity of antioxidant 
enzymes. These findings hold potential for developing a cost-effective method 
for commercial ajmalicine production. Plants possess an intrinsic ability to 
detect various stress signals, prompting the activation of defense mechanisms 
through the reprogramming of metabolites to counter adverse conditions. The 
current study aims to propose an optimized bioprocess for enhancing the content 
of ajmalicine in Rauwolfia serpentina callus through elicitation with 
phytosynthesized silver nanoparticles. Initially, callus lines exhibiting 
elevated ajmalicine content were established. Following this, a protocol for the 
phytosynthesis of silver nanoparticles using seed extract from Rauwolfia 
serpentina was successfully standardized. The physicochemical attributes of the 
silver nanoparticles were identified, including their spherical shape, size 
ranging from 6.7 to 28.8 nm in diameter, and the presence of reducing-capping 
groups such as amino, carbonyl, and amide. Further, the findings indicated that 
the presence of 2.5 mg L-1 phytosynthesized silver nanoparticles in the culture 
medium increased the ajmalicine content. Concurrently, structural genes (TDC, 
SLS, STR, SGD, G10H) and regulatory gene (ORCA3) associated with the ajmalicine 
biosynthetic pathway were observed to be upregulated. A notable increase in MDA 
content and a decrease in the activities of antioxidant enzymes were observed. A 
notable increase in MDA content and a decrease in the activities of antioxidant 
enzymes were also observed. Our results strongly recommend the augmentation of 
ajmalicine content in the callus culture of R. serpentina through 
supplementation with silver nanoparticles, a potential avenue for developing a 
cost-effective process for the commercial production of ajmalicine.

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
part of Springer Nature.

DOI: 10.1007/s00425-023-04311-z
PMID: 38150044 [Indexed for MEDLINE]


2. J Biochem Mol Toxicol. 2024 Jan;38(1):e23614. doi: 10.1002/jbt.23614. Epub
2023  Dec 8.

Ajmalicine induces the pyroptosis of hepatoma cells to exert the antitumor 
effect.

Sun Z(1), Ma C(1), Zhan X(1).

Author information:
(1)Pharmacy Department, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang Province, 
China.

Ajmalicine (AJM) is an alkaloid extracted from the root of Yunan Rauvolfia 
verticillata. At present, little research has reported the antitumor 
pharmacological action and mechanism of AJM. Therefore, this work aimed to 
conduct relevant research. The mouse hepatoma cell line H22 was intervened with 
a gradient concentration of AJM. Subsequently, the pyroptosis level was detected 
by flow cytometry. The expression of inflammatory factors and lactate 
dehydrogenase was measured by enzyme-linked immunosorbent assay. Reactive oxygen 
species (ROS) expression was detected by dichlorodihydrofluorescein diacetate 
probe. In addition, the tumor-bearing model mice were also treated with AJM to 
analyze tumor growth as well as the expression levels of tissue inflammatory 
factors and proteins. According to our results, AJM promoted the pyroptosis of 
H22 cells, increased the pyroptosis rate, and upregulated the expression of 
inflammatory factors tumor necrosis factor α, interleukin-1β, and interleukin-6. 
At the same time, it enhanced the openness of membrane pores and increased the 
expression of ROS. Moreover, AJM promoted the expression of Caspase-3 and 
N-terminal gasdermin E (GSDME). The AJM-induced pyroptosis was suppressed after 
N-acetylcysteine treatment to inhibit ROS, while Caspase-3 knockdown also 
inhibited the AJM-induced pyroptosis. In animals, AJM suppressed tumor growth. 
AJM can activate ROS to induce pyroptosis and exert the antitumor effect via the 
noncanonical Caspase-3-GSDME pyroptosis pathway.

© 2023 Wiley Periodicals LLC.

DOI: 10.1002/jbt.23614
PMID: 38064316 [Indexed for MEDLINE]


3. Eur J Pharmacol. 2024 Jan 5;962:176251. doi: 10.1016/j.ejphar.2023.176251.
Epub  2023 Dec 5.

Tetrahydroalstonine possesses protective potentials on palmitic acid stimulated 
SK-N-MC cells by suppression of Aβ1-42 and tau through regulation of PI3K/Akt 
signaling pathway.

Chen K(1), Yu G(2).

Author information:
(1)Department of Neurology, Jiangsu Traditional Chinese Medicine Hospital, The 
Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 
Nanjing, 210029, PR China.
(2)Department of Neurology, Jiangsu Traditional Chinese Medicine Hospital, The 
Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 
Nanjing, 210029, PR China. Electronic address: yushengzh@126.com.

Alzheimer's disease (AD) is the most common neurodegenerative disease. The 
morbidity of Alzheimer's disease is currently on the rise worldwide, but no 
effective treatment is available. Cornus officinalis is an herb and edible plant 
used in traditional Chinese medicine, whose extract has neuroprotective 
properties. In this investigation, we endeavored to refine a systems 
pharmacology strategy combining bioinformatics analysis, drug prediction, 
network pharmacology, and molecular docking to screen tetrahydroalstonine (THA) 
from Cornus officinalis as a therapeutic component for AD. Subsequent in vitro 
experiments were validated using MTT assay, Annexin V-PI flow cytometry, Western 
blotting, and immunofluorescence analysis. In Palmitate acid-induced SK-N-MC 
cells, THA restored the impaired PI3K/AKT signaling pathway, regulated insulin 
resistance, and attenuated BACE1 and GSK3β activity. In addition, THA 
significantly reduced cell apoptosis rate, down-regulated relative levels of 
p-JNK/JNK, Bax/Bcl-2, cytochrome C, active caspase-3 and caspase-3, and 
attenuated Palmitate acid-induced Aβ1-42 and Tau generation. THA may regulate 
the phenotype of AD and reduce cell apoptosis by modulating the PI3K/AKT 
signaling pathway. This systematic analysis provides new ramifications 
concerning the therapeutic utility of tetrahydroalstonine for AD.

Copyright © 2023 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.ejphar.2023.176251
PMID: 38061471 [Indexed for MEDLINE]

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.


4. Molecules. 2023 Mar 4;28(5):2370. doi: 10.3390/molecules28052370.

The Protective Effect of (-)-Tetrahydroalstonine against OGD/R-Induced Neuronal 
Injury via Autophagy Regulation.

Liao Y(1)(2), Wang JY(3), Pan Y(2), Zou X(2)(3), Wang C(2), Peng Y(2), Ao YL(3), 
Lam MF(4), Zhang X(1), Zhang XQ(3)(5), Shi L(1)(2), Zhang S(2).

Author information:
(1)Department of Cardiovascular Surgery, The First Affiliated Hospital, Jinan 
University, Guangzhou 510632, China.
(2)JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, 
College of Pharmacy, Jinan University, Guangzhou 510632, China.
(3)Guangdong Provincial Engineering Research Center for Modernization of TCM, 
College of Pharmacy, Jinan University, Guangzhou 510632, China.
(4)Centro Hospitalar Conde de São Januário, Macau, China.
(5)NMPA Key Laboratory for Quality Evaluation of TCM, Jinan University, 
Guangzhou 510632, China.

Here, (-)-Tetrahydroalstonine (THA) was isolated from Alstonia scholaris and 
investigated for its neuroprotective effect towards oxygen-glucose 
deprivation/re-oxygenation (OGD/R)-induced neuronal damage. In this study, 
primary cortical neurons were pre-treated with THA and then subjected to OGD/R 
induction. The cell viability was tested by the MTT assay, and the states of the 
autophagy-lysosomal pathway and Akt/mTOR pathway were monitored by Western blot 
analysis. The findings suggested that THA administration increased the cell 
viability of OGD/R-induced cortical neurons. Autophagic activity and lysosomal 
dysfunction were found at the early stage of OGD/R, which were significantly 
ameliorated by THA treatment. Meanwhile, the protective effect of THA was 
significantly reversed by the lysosome inhibitor. Additionally, THA 
significantly activated the Akt/mTOR pathway, which was suppressed after OGD/R 
induction. In summary, THA exhibited promising protective effects against 
OGD/R-induced neuronal injury by autophagy regulation through the Akt/mTOR 
pathway.

DOI: 10.3390/molecules28052370
PMCID: PMC10005631
PMID: 36903613 [Indexed for MEDLINE]

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


5. Biotechnol Bioeng. 2022 May;119(5):1314-1326. doi: 10.1002/bit.28040. Epub
2022  Jan 31.

Construction of ajmalicine and sanguinarine de novo biosynthetic pathways using 
stable integration sites in yeast.

Liu T(1), Gou Y(1)(2), Zhang B(1), Gao R(1)(2), Dong C(1)(2), Qi M(1), Jiang 
L(1), Ding X(3), Li C(3), Lian J(1)(2).

Author information:
(1)Key Laboratory of Biomass Chemical Engineering of Ministry of Education, 
Zhejiang University, Hangzhou, China.
(2)Hangzhou Global Scientific and Technological Innovation Center, Zhejiang 
University, Hangzhou, China.
(3)Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, 
Ministry of Industry and Information Technology, Institute of Biochemical 
Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of 
Technology, Beijing, China.

Yeast cell factories have been increasingly employed for producing plant-derived 
natural products. Unfortunately, the stability of plant natural product 
biosynthetic pathway genes, particularly when driven by the same sets of 
promoters and terminators, remains one of the biggest concerns for synthetic 
biology. Here we profile genomic loci flanked by essential genes as stable 
integration sites in a genome-wide manner, for stable maintenance of multigene 
biosynthetic pathways in yeast. We demonstrate the application of our yeast 
integration platform in the construction of sanguinarine (24 expression 
cassettes) and ajmalicine (29 expression cassettes) de novo biosynthetic 
pathways for the first time. Moreover, we establish stable yeast cell factories 
that can produce 119.2 mg L-1 heteroyohimbine alkaloids (containing 61.4 mg L-1 
ajmalicine) in shake flasks, representing the highest titer of monoterpene 
indole alkaloids (MIAs) ever reported and promising the complete biosynthesis of 
other high-value MIAs (such as vinblastine) for biotechnological applications.

© 2022 Wiley Periodicals LLC.

DOI: 10.1002/bit.28040
PMID: 35060115 [Indexed for MEDLINE]