Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. In Silico Pharmacol. 2024 Nov 2;12(2):97. doi: 10.1007/s40203-024-00269-2. 
eCollection 2024.

Effects of some anti-ulcer and anti-inflammatory natural products on 
cyclooxygenase and lipoxygenase enzymes: insights from in silico analysis.

Metuge JA(1), Betow JY(2)(3), Bekono BD(2)(4), Tjegbe MJM(2), Ndip RN(2)(5), 
Ntie-Kang F(2)(3)(6).

Author information:
(1)Department of Natural Resources and Environmental Sciences, Alabama A&M 
University, Huntsville, USA.
(2)Center for Drug Discovery, Faculty of Science, University of Buea, Buea, 
Cameroon.
(3)Department of Chemistry, Faculty of Science, University of Buea, Buea, 
Cameroon.
(4)Department of Physics, Ecole Normale Supérieure, University of Yaoundé I, 
Yaoundé, Cameroon.
(5)Department of Microbiology and Parasitology, Faculty of Science, University 
of Buea, Buea, Cameroon.
(6)Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, 
Kurt-Mothes-Strasse 3, 06120 Halle (Saale), Germany.

Gastric and duodenal ulcers are increasingly becoming global health burdens. The 
side effects of conventional treatments such as non-steroid anti-inflammatory 
drugs (NSAIDs), proton pump inhibitors (PPIs), antibiotics, and cytoprotective 
agents have necessitated the search for new medications. Plants are a rich 
source of active metabolites and herbal medicines have been used in the 
treatment of ulcers and cancers. In this study, we used in silico methods like 
molecular docking and MM-GBSA calculations to evaluate the effects of some 
anti-ulcer and anti-inflammatory phytochemicals on some key enzymes, 
cyclooxygenase (COX), and lipoxygenase (LOX), which are implicated in the 
protection and destruction of the gastric mucosa. The phytochemicals were 
retrieved from the literature and docked toward the binding sites of the three 
enzymes (COX-1, COX-2, and 5-LOX). Five compounds, rhamnetin, kaempferol, rutin, 
rosmarinic acid, and chlorogenic acid were observed to putatively bind to 
cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) but not to cyclooxygenase 1 
(COX-1). The interaction mechanisms between these phytochemicals and the target 
proteins are discussed. The compounds' drug metabolism, pharmacokinetics, and 
toxicity have been evaluated to assess their suitability as potential 
next-generation anti-ulcer and anti-inflammatory drugs.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material 
available at 10.1007/s40203-024-00269-2.

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part 
of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or 
other partner) holds exclusive rights to this article under a publishing 
agreement with the author(s) or other rightsholder(s); author self-archiving of 
the accepted manuscript version of this article is solely governed by the terms 
of such publishing agreement and applicable law.

DOI: 10.1007/s40203-024-00269-2
PMCID: PMC11531464
PMID: 39498163

Conflict of interest statement: Competing interestThe authors declare that they 
have no conflicts of interest.


2. Phytochem Anal. 2024 Nov 4. doi: 10.1002/pca.3471. Online ahead of print.

An Integrated Approach to Identify the Q-Markers of Banxia-Houpo Decoction Based 
on Nontargeted Multicomponent Profiling, Network Pharmacology, and Chemometrics.

Wang L(1)(2), Wu W(3), Li G(1), Chen H(1), Fan Y(3), Chen W(4), Zhou G(4), Li 
W(1)(2).

Author information:
(1)College of Pharmaceutical Engineering of Traditional Chinese Medicine, 
Tianjin University of Traditional Chinese Medicine, Tianjin, China.
(2)Tianjin Key Laboratory of Intelligent and Green Pharmaceuticals for 
Traditional Chinese Medicine, Tianjin, China.
(3)Jiuxin (Wuhan) Institute of Traditional Chinese Medicine Co. Ltd., Wuhan, 
China.
(4)Shanghai Zhen Ren Tang Pharmaceutical Co. Ltd., Shanghai, China.

INTRODUCTION: The inherent complexity of traditional Chinese medicine (TCM) 
poses significant challenges in directly correlating quality evaluation with 
clinical efficacy. Banxia-Houpo Decoction (BHD), a classical TCM formula, has 
demonstrated efficacy in treating globus hystericus. However, the intricate 
composition of BHD, which contains both volatile and non-volatile active 
components, complicates efforts to ensure its consistent quality and clinical 
effectiveness.
OBJECTIVE: The aim of this study was to introduce an integrated approach that 
combines non-targeted multicomponent analysis, network pharmacology, and 
multivariate chemometrics to identify quality markers for the effective quality 
control of BHD.
MATERIALS AND METHODS: First, a nontargeted high-definition MSE method based on 
ultraperformance liquid chromatography-quadrupole time-of-flight-mass 
spectrometry (UHPLC-QTOF-MS) was developed for the comprehensive multi-component 
characterization of BHD. Next, the quality markers of nonvolatile compounds in 
BHD were identified through network pharmacology analysis. Subsequently, 
volatile organic compounds (VOCs) in BHD samples were analyzed via headspace 
solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) 
and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). Finally, 
the orthogonal partial least squares discriminant analysis (OPLS-DA) model was 
applied to screen for potential markers.
RESULTS: Based on in-house library-driven automated peak annotation and 
comparison with 25 reference compounds, 128 components were identified for the 
first time. Additionally, honokiol, magnolol, magnoflorine, 6-gingerol, 
rosmarinic acid, and adenosine were preliminarily identified as potential 
quality markers for BHD through network pharmacology analysis. By employing two 
complementary techniques, HS-SPME-GC-MS and HS-GC-IMS, a total of 145 volatile 
compounds was identified in the BHD samples. Four potential differential VOCs in 
the BHD samples were further identified based on the variable importance in 
projection (VIP ≥ 1.5) using HS-GC-IMS combined with chemometric analysis.
CONCLUSION: In conclusion, this study not only contributes to establishing 
quality standards for BHD but also offers new insights into quality assessment 
and identification in the development of classical formulations enriched with 
volatile components.

© 2024 John Wiley & Sons Ltd.

DOI: 10.1002/pca.3471
PMID: 39497523


3. J Ethnopharmacol. 2024 Oct 25:118991. doi: 10.1016/j.jep.2024.118991. Online 
ahead of print.

Phytochemical analysis and evaluation of the inhibitory effect of the Cunila 
lythrifolia Benth aerial parts on abdominal pain and some digestive enzymes.

Flores-Bocanegra L(1), González-Hernández EE(2), Soto-Sosa A(2), 
González-Trujano ME(3), Cristians S(4).

Author information:
(1)Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de 
México 04510, México. Electronic address: lcflores_bocanegra@quimica.unam.mx.
(2)Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de 
México 04510, México.
(3)Laboratorio de Neurofarmacología de Productos Naturales, Dirección de 
Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la 
Fuente Muñiz, Ciudad de México 14370, México.
(4)Jardín Botánico, Instituto de Biología, Universidad Nacional Autónoma de 
México. Universidad Nacional Autónoma de México, Ciudad de México 04510, México.

ETHNOPHARMACOLOGY RELEVANCE: Cunila lythrifolia Benth. (Lamiaceae) commonly 
named "poleo de monte" is a Mexican plant known since pre-Hispanic times because 
of the properties of its aerial parts to treat respiratory and gastrointestinal 
conditions, for postpartum care, and as an aphrodisiac.
AIM OF THE STUDY: To obtain preclinical evidence of the pharmacological 
properties of C. lythrifolia on abdominal pain and some digestive enzymes, as 
well as its chemical composition.
MATERIAL AND METHODS: The preclinical safety of a decoction was evaluated by the 
Lorke method in mice. The antinociceptive effect was assessed using the acetic 
acid-induced writhing test in mice, and the mechanism of action was explored by 
the co-administration of naloxone. Additionally, the inhibition of the lipase 
and α-amylase was carried out using a colorimetric assay to calculate the 
percentage of inhibition. The isolation of specialized metabolites was carried 
out using chromatographic techniques, and characterization was established with 
MS, NMR, and chiroptical analysis. The volatile components of the aerial parts 
were identified by GC-MS analysis of the essential oils, and by HSPM coupled 
with GC-MS. An analytical method by UHPLC was validated under the guidelines of 
the ICH, for the quantification of 1.
RESULTS: The LD50 of the aqueous extract is higher than 5g/kg. The decoction and 
the essential oil have an antinociceptive effect at 100 and 10 mg/kg, 
respectively. The essential oil was active against the lipase enzyme (96-76 % of 
inhibition). The isolated compounds from the decoction were linarin (1), 
7-O-[2-O-acetyl-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside] 
(2), lithospermic acid (3), rosmarinic acid (4), and citrusin C (5). Compound 1 
showed an antinociceptive effect at 316 mg/kg. A UHPLC method was validated for 
the quantification of 1 in three different batches. The volatiloma analysis 
revealed that menthofuran (10), β-caryophyllene (22), spathulenol (31), and 
caryophyllene oxide (32) are the major constituents in the aerial parts. 
(±)-cunildone (27) a new menthofuran derivative was isolated from the essential 
oil of the fresh aerial parts.
CONCLUSION: The results of these studies demonstrate the preclinical safety and 
validate the traditional use of C. lythrifolia as an antinociceptive agent. 
Contribute to the chemical identification of the species and to the quality 
control and establish a method for quantitative analysis of the plant. Overall 
promoting the rational use and quality control of C. lythrifolia.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.jep.2024.118991
PMID: 39490712

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. Gene. 2024 Oct 26:149057. doi: 10.1016/j.gene.2024.149057. Online ahead of 
print.

Analysis of rosmarinic acid synthase (RAS) gene family and functional study of 
SmRAS1/2/4 in Salvia miltiorrhiza.

Xin Y(1), Zhan H(1), Kang H(1), Li Q(1), Fu F(1), Han L(2), Hua W(3), Cao X(4).

Author information:
(1)Key Laboratory of the Ministry of Education for Medicinal Resources and 
Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource 
Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal 
University, Xi'an 710119, China.
(2)College of Life Science and Food Engineering, Shaanxi Xueqian Normal 
University, Xi'an 710100, China.
(3)College of Life Science and Food Engineering, Shaanxi Xueqian Normal 
University, Xi'an 710100, China. Electronic address: huawenping@126.com.
(4)Key Laboratory of the Ministry of Education for Medicinal Resources and 
Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource 
Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal 
University, Xi'an 710119, China. Electronic address: caoxiaoyan@snnu.edu.cn.

Rosmarinic acid synthase is an essential enzyme involved in the biosynthesis of 
rosmarinic acid (RA), which facilitates the coupling of phenylpropanoid and 
tyrosine-derived pathway products. Our study identified six SmRAS genes in 
Salvia miltiorrhiza, with SmRAS1 being the only one functionally characterized 
to date. Real-time quantitative PCR was employed to analyze the expression 
profiles of the SmRAS gene family, revealing that SmRAS1/2/4 are predominantly 
expressed in the roots, which are the medicinal components of S. miltiorrhiza. 
SmRAS2 and SmRAS4 exhibited significant responses to abscisic acid (ABA), 
gibberellin (GA3), and methyl jasmonate (MeJA) stimuli, while SmRAS1 had notable 
responses to GA3 and MeJA. β-glucuronidase (GUS) staining in transgenic 
Arabidopsis thaliana confirmed a spatiotemporal expression pattern of SmRAS1/2/4 
that was consistent with the qRT-PCR results. SmRAS1/2/4 are primarily localized 
to the cytoplasm and plasma membrane. Our findings suggested that the 
overexpressions of SmRAS1 or SmRAS4 led to increased levels of salvianolic acid 
B (SalB) and RA, with a concomitant decrease in the Danshensu (DSS) content, 
which served as a substrate. In contrast, RNA interference lines exhibited a 
downward trend in the content of these substances. Interestingly, no significant 
changes were detected in the SalB, RA, or DSS contents due to the overexpression 
of SmRAS2 or RNA interference lines. Collectively, our study demonstrated that 
SmRAS1 and SmRAS4 are key regulators of RA and SalB biosynthesis in S. 
miltiorrhiza, while SmRAS2's role appears less impactful, suggesting a complex 
regulatory network that influences the medicinal properties of this plant.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.gene.2024.149057
PMID: 39490649

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.


5. Phytomedicine. 2024 Oct 28;135:156182. doi: 10.1016/j.phymed.2024.156182.
Online  ahead of print.

A stepwise integrated strategy to explore quality markers of Qishen Yiqi 
dripping pills against myocardial ischemia.

Liu LW(1), Tang M(2), Zhang ZB(1), Zhou PP(1), Xue LP(1), Jia QQ(1), Zhao LG(3), 
Zuo LH(4), Sun Z(5).

Author information:
(1)Department of Pharmacy, the First Affiliated Hospital of Zhengzhou 
University, Zhengzhou, Henan Province, 450052, PR China; Henan Engineering 
Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, 
Henan Province, 450052, PR China.
(2)The First Department of Orthopaedics, Zhengzhou Central Hospital Affiliated 
to Zhengzhou University, Zhengzhou, Henan Province, 450007, PR China.
(3)Center for Disease Prevention and Control of Baoan District, Shenzhen, 
Guangdong Province, 518101, PR China.
(4)Department of Pharmacy, the First Affiliated Hospital of Zhengzhou 
University, Zhengzhou, Henan Province, 450052, PR China; Henan Engineering 
Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, 
Henan Province, 450052, PR China. Electronic address: zuolihua2013@126.com.
(5)Department of Pharmacy, the First Affiliated Hospital of Zhengzhou 
University, Zhengzhou, Henan Province, 450052, PR China; Henan Engineering 
Research Center of Clinical Mass Spectrometry for Precision Medicine, Zhengzhou, 
Henan Province, 450052, PR China. Electronic address: sunzhi2013@163.com.

BACKGROUND: Numerous experiments and clinical practices have demonstrated the 
effectiveness of Qishen Yiqi dripping pills (QSYQ) on myocardial ischemia (MI). 
However, the bioactive ingredients and mechanisms remain unclear, leading to 
huge gaps between quality control and biological effect of QSYQ. Discovering 
quality markers (Q-markers) based on effective components is crucial for 
ensuring stable quality and clinical effectiveness of QSYQ.
PURPOSE: To explore Q-markers of QSYQ against MI by a stepwise strategy 
integrating serum pharmacochemistry, network pharmacology, metabolomics, 
quantitative analysis, and cell experiments.
METHODS: Firstly, liquid/gas chromatography-mass spectrometry was applied to 
characterize chemical profiles of QSYQ in vitro and in vivo. Based on the serum 
migrating constituents, a component-target-MI interaction network was 
constructed. Subsequently, pharmacodynamics and metabolomics were conducted to 
evaluate cardioprotective effect and potential mechanism of QSYQ. Next, conjoint 
analysis of network pharmacology and metabolomics was performed to screen 
candidate Q-markers. Finally, the measurability and bioactivity were validated 
to justify their usage as Q-markers.
RESULTS: A total of 97 components were identified in QSYQ, 24 prototypes of 
which were detected in serum. The "component-target-disease" interaction network 
was constructed based on serum migrating constituents. Pharmacodynamic results 
showed that QSYQ effectively improved cardiac function, attenuated inflammatory 
cell infiltration, alleviated myocardial fibrosis, and reduced the levels of 
myocardial enzymes and oxidative stress in MI rats. Metabolomics study 
demonstrated that 59 metabolites were markedly altered in MI rats, 25 of which 
were significantly reversely regulated by QSYQ. After integrative analysis of 
network pharmacology and metabolomics, 12 components were selected as candidate 
Q-markers of QSYQ, and the contents were quantified. These candidate Q-markers 
displayed synergistic protective effects against H2O2-induced injury in H9c2 
cells. Taken together, 12 components with properties of transitivity and 
traceability, effectiveness, measurability, and compatibility contribution were 
defined as representative Q-markers of QSYQ, including Astragaloside IV, Ononin, 
Calycosin, Formononetin, Rosmarinic acid, Cryptotanshinone, Salvianolic acid A, 
Tanshinol, Ginsenoside Rb1, Ginsenoside Rg1, Nerolidol, and Santalol.
CONCLUSION: In this study, a novel stepwise integrated strategy was presented 
for discovering Q-markers related to therapeutic effects of traditional Chinese 
medicine prescriptions. Twelve comprehensive and representative Q-markers of 
QSYQ were identified for the first time to improve its quality control.

Copyright © 2024 Elsevier GmbH. All rights reserved.

DOI: 10.1016/j.phymed.2024.156182
PMID: 39488103

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.