Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Org Biomol Chem. 2023 Oct 18;21(40):8190-8196. doi: 10.1039/d3ob01424j.

Alscholarines A and B, two rearranged monoterpene indole alkaloids from Alstonia 
scholaris.

Zhan G(1), Zhang F(1), Yang K(1), Yang T(1), Zhou R(1), Chen W(1), Zhang J(1), 
Zhang X(1), Guo Z(1).

Author information:
(1)School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 
710061, P.R. China. guozj@mail.xjtu.edu.cn.

Alscholarines A and B (1 and 2), two unprecedented rearranged monoterpene indole 
alkaloids, were isolated from Alstonia scholaris. Alscholarine A (1) features an 
imidazole ring fused with a rearranged vallesamine-type alkaloid possessing an 
unparalleled 6/5/6/6 tetracyclic skeleton through an unprecedented C7-C-19 
connectivity. Alscholarine B (2), incorporating an unusual 
7-oxa-1-azabicyclo[3.2.1]octane moiety, represents a unique rearranged 
vallesamine-type alkaloid with a 6/5/6/6/5 ring system via an unprecedented 
C-6-C-20 connectivity. Their structures were established by spectroscopic 
analysis, X-ray crystallography, and quantum-chemical calculations. Their 
plausible biosynthetic pathways were proposed. The vasorelaxant and 
anti-inflammatory activities of them were also evaluated. Compounds 1-3 showed 
moderate vasorelaxant activities.

DOI: 10.1039/d3ob01424j
PMID: 37788053 [Indexed for MEDLINE]


2. Phytomedicine. 2023 Sep;118:154958. doi: 10.1016/j.phymed.2023.154958. Epub
2023  Jul 8.

Pharmacological investigation of indole alkaloids from Alstonia scholaris 
against chronic glomerulonephritis.

Guo R(1), Shang JH(2), Ye RH(3), Zhao YL(4), Luo XD(5).

Author information:
(1)Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of 
Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan 
Province, School of Chemical Science and Technology, Yunnan University, Kunming 
650500, PR China; Chinese Materia Medica, Yunnan University of Chinese Medicine, 
Kunming 650500, PR China.
(2)State Key Laboratory of Phytochemistry and Plant Resources in West China, 
Kunming Institute of Botany, Chinese Academy of Sciences Kunming 650201, PR 
China.
(3)Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 
650500, PR China.
(4)Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of 
Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan 
Province, School of Chemical Science and Technology, Yunnan University, Kunming 
650500, PR China. Electronic address: zhaoyunli@ynu.edu.cn.
(5)Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of 
Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan 
Province, School of Chemical Science and Technology, Yunnan University, Kunming 
650500, PR China; State Key Laboratory of Phytochemistry and Plant Resources in 
West China, Kunming Institute of Botany, Chinese Academy of Sciences Kunming 
650201, PR China. Electronic address: xdluo@ynu.edu.cn.

BACKGROUND: As one of the most commonly used folk medicines in "Dai" 
ethno-medicine system, Alstonia scholaris (l.) R. Br. has also been used for 
treat "water related diseases", such as chronic kidney disease. However, few 
study was reported for it on the intervention of chronic glomerulonephritis 
(CGN).
PURPOSE: To investigate the effect and potential mechanism of indole alkaloids 
from A. scholaris leaves in ICR mice with adriamycin nephropathy, as well as 
providing experimental evidence for the further application.
METHODS: ICR Mice were selected for injections of adriamycin (ADR) to induce the 
CGN model and administered total alkaloids (TA) and four main alkaloids 
continuously for 42 and 28 days, respectively. The pharmacological effects were 
indicated by serum, urine, and renal pathological observations. The targets and 
pathways of indole alkaloids on CGN intervention were predicted using the 
network pharmacology approach, and the immortalized mice glomerular podocyte 
(MPC5) cells model stimulated by ADR was subsequently selected to further verify 
this by western blotting and RT-qPCR methods.
RESULTS: TA and four major compounds dramatically reduced the levels of urinary 
protein, serum urea nitrogen (BUN), and creatinine (CRE) in ADR - induced CGN 
mice, while increasing serum albumin (ALB) and total protein (TP) levels as well 
as ameliorating kidney damage. Moreover, four alkaloids effected on 33 major 
target proteins and 153 pathways in the CGN, among which, PI3K-Akt as the main 
pathway, an important pathway for kidney protection by network pharmacology 
prediction, and then the four target proteins - HRAS, CDK2, HSP90AA1, and KDR 
were screened. As a result, Val-and Epi can exert a protective effect on 
ADR-stimulated MPC5 cells injury at a concentration of 50 μM. Furthermore, the 
proteins and RNA expression of HRAS, HSP90AA1, and KDR were down-regulated, and 
CDK2 was up-regulated after the intervention of Val-and Epi, which were 
supported by Western blotting and RT-qPCR. Additionally, Val-and Epi inhibited 
ROS production in the MPC5 cells model.
CONCLUSION: This study is the first to confirm the potential therapeutic effect 
of alkaloids from A. scholaris on CGN. TA with major bioactive components 
(vallesamine and 19‑epi-scholaricine) could exert protective effects against the 
ADR-induced CGN by regulating four key proteins: HRAS, CDK2, HSP90AA1, and KDR 
of the PI3K-Akt pathway.

Copyright © 2023 Elsevier GmbH. All rights reserved.

DOI: 10.1016/j.phymed.2023.154958
PMID: 37453192 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest We reaffirm 
that this publication has no known conflicts of interest and has received no 
substantial financial assistance that would have affected the research's 
conclusion.


3. J Sep Sci. 2023 Sep;46(17):e2200843. doi: 10.1002/jssc.202200843. Epub 2023
Jun  22.

Targeted quantitative analysis of monoterpenoid indole alkaloids in Alstonia 
scholaris by ultra-high-performance liquid chromatography coupled with 
quadrupole time of flight mass spectrometry.

Qin Y(#)(1), He YJ(#)(1)(2), Zhao YL(1), Zhou ZS(1), Wang ZJ(1), Zhu YY(1), Luo 
XD(1)(3).

Author information:
(1)Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of 
Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan 
Province, School of Chemical Science and Technology, Yunnan University, Kunming, 
P. R. China.
(2)State Environmental Protection Key Laboratory of Integrated Surface 
Water-Groundwater Pollution Control, School of Environmental Science and 
Engineering, Southern University of Science and Technology, Shenzhen, P. R. 
China.
(3)State Key Laboratory of Phytochemistry and Plant Resources in West China, 
Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, P. R. China.
(#)Contributed equally

Monoterpene indole alkaloids exhibit structural diversity in herbal resources 
and have been developed as promising drugs owing to their significant biological 
activities. Confidential identification and quantification of monoterpene indole 
alkaloids is the key to quality control of target plants in industrial 
production but has rarely been reported. In this study, quantitative performance 
of three data acquisition modes of ultra-high-performance liquid chromatography 
coupled with quadrupole time-of-flight mass spectrometry including full scan, 
auto-MS2 and target-MS2 , was evaluated and compared for specificity, 
sensitivity, linearity, precision, accuracy, and matrix effect using five 
monoterpene indole alkaloids (scholaricine, 19-epi-scholaricine, vallesamine, 
picrinine, and picralinal). Method validations indicated that target-MS2 mode 
showed predominant performance for simultaneous annotation and quantification of 
analytes, and was then applied to determine monoterpene indole alkaloids in 
Alstonia scholaris (leaves, barks) after extraction procedures optimization 
using Box-Behnken design of response surface methodology. The variations of A. 
scholaris monoterpene indole alkaloids in different plant parts, harvest 
periods, and post-handling processes, were subsequently investigated. The 
results indicated that target-MS2 mode could improve the quantitative capability 
of ultra-high-performance liquid chromatography coupled with quadrupole 
time-of-flight mass spectrometry for structure-complex monoterpene indole 
alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, 
quadrupole time of flight mass spectrometry, qualitative and quantitative 
analysis, ultra-high-performance liquid chromatography.

© 2023 Wiley-VCH GmbH.

DOI: 10.1002/jssc.202200843
PMID: 37349854 [Indexed for MEDLINE]


4. Nat Prod Rep. 2023 May 24;40(5):1022-1044. doi: 10.1039/d2np00052k.

Chemistry, bioactivity, biosynthesis, and total synthesis of stemmadenine 
alkaloids.

Fan M(1), Zou L(1), Tian K(1), Chen G(1), Cheng K(1), Li Y(1).

Author information:
(1)Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals 
Process, Shaoxing University, Shaoxing, 312000, People's Republic of China. 
liyong@usx.edu.cn.

Covering: up to July 2022Stemmadenine alkaloids are a restrictive sub-group of 
monoterpene indole alkaloids, represented by two congeners: stemmadenine and 
vallesamine. Their skeleton is defined by the cleavage of the C-3-C-7 bond of 
the Strychnos group's pentacyclic scaffold in monoterpene indole alkaloids. The 
parent alkaloid stemmadenine acts as a key intermediate in the biosynthesis of 
several major monoterpene indole alkaloid families, including regular Strychnos 
alkaloids, Aspidosperma alkaloids, and Iboga alkaloids. In this review, a 
complete coverage of the stemmadenine alkaloids, from the early reports till the 
present day at 2022, are presented, and their diverse biological activities are 
briefly described. Moreover, the biosynthetic proposal for stemmadenine and the 
proposed biogenetic conversion of stemmadenine-type alkaloids into 
vallesamine-type congeners are discussed in detail. Moreover, the successful 
synthetic strategies to access the strained stemmadenine scaffolds are fully 
reviewed.

DOI: 10.1039/d2np00052k
PMID: 36728407 [Indexed for MEDLINE]


5. Antibiotics (Basel). 2022 Aug 24;11(9):1146. doi: 10.3390/antibiotics11091146.

Antibacterial and Antifungal Alkaloids from Asian Angiosperms: Distribution, 
Mechanisms of Action, Structure-Activity, and Clinical Potentials.

Sulaiman M(1), Jannat K(2), Nissapatorn V(3), Rahmatullah M(2), Paul AK(4), de 
Lourdes Pereira M(5), Rajagopal M(6), Suleiman M(7), Butler MS(8), Break MKB(9), 
Weber JF(10), Wilairatana P(11), Wiart C(7).

Author information:
(1)Department of Chemistry, Faculty of Science, University of Malaya, Kuala 
Lumpur 50603, Malaysia.
(2)Department of Biotechnology & Genetic Engineering, University of Development 
Alternative, Dhaka 1207, Bangladesh.
(3)School of Allied Health Sciences and World Union for Herbal Drug Discovery 
(WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand.
(4)School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 
7001, Australia.
(5)CICECO-Aveiro Institute of Materials & Department of Medical Sciences, 
University of Aveiro, 3810-193 Aveiro, Portugal.
(6)Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, 
Malaysia.
(7)Institute for Tropical Biology & Conservation, Universiti Malaysia Sabah, 
Kota Kinabalu 88400, Malaysia.
(8)MSBChem Consulting, Brisbane, QLD 4005, Australia.
(9)Department of Pharmaceutical Chemistry, College of Pharmacy, University of 
Hail, Hail 81411, Saudi Arabia.
(10)UFR Sciences Pharmaceutiques, INRAE, Bordeaux INP, UR ŒNOLOGIE, EA 4577, USC 
1366, ISVV, Université de Bordeaux, 210 Chemin de Leysotte, 33882 Villenave 
d'Ornon, France.
(11)Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, 
Mahidol University, Bangkok 10400, Thailand.

The emergence of multidrug-resistant bacteria and fungi requires the development 
of antibiotics and antifungal agents. This review identified natural products 
isolated from Asian angiosperms with antibacterial and/or antifungal activities 
and analyzed their distribution, molecular weights, solubility, and modes of 
action. All data in this review were compiled from Google Scholar, PubMed, 
Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 
1979 to 2022. One hundred and forty-one antibacterial and/or antifungal 
alkaloids were identified during this period, mainly from basal angiosperms. The 
most active alkaloids are mainly planar, amphiphilic, with a molecular mass 
between 200 and 400 g/mol, and a polar surface area of about 50 Å2, and target 
DNA and/or topoisomerase as well as the cytoplasmic membrane. 
8-Acetylnorchelerythrine, cryptolepine, 8-hydroxydihydrochelerythrine, 
6-methoxydihydrosanguinarine, 2'-nortiliacorinine, pendulamine A and B, 
rhetsisine, sampangine, tiliacorine, tryptanthrin, tylophorinine, vallesamine, 
and viroallosecurinine yielded MIC ≤ 1 µg/mL and are candidates for the 
development of lead molecules.

DOI: 10.3390/antibiotics11091146
PMCID: PMC9495154
PMID: 36139926

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