Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Biomol Struct Dyn. 2024 Feb 9:1-23. doi: 10.1080/07391102.2024.2308773.
Online  ahead of print.

A discovery of potent kaempferol derivatives as multi-target medicines against 
diabetes as well as bacterial infections: an in silico approach.

Parveen S(1), Shehzadi S(1), Shafiq N(1), Rashid M(1), Naz S(2), Mehmood T(3), 
Riaz R(1), S Almaary K(4), Nafidi HA(5), Bourhia M(6).

Author information:
(1)Synthetic and Natural Product Drug Discovery Laboratory, Department of 
Chemistry, Government College Women University, Faisalabad, Pakistan.
(2)Department of Chemistry, The University of Lahore, Lahore, Pakistan.
(3)Centre for Applied Molecular Biology (CAMB), University of the Punjab, 
Punjab, Pakistan.
(4)Department of Botany and Microbiology, College of Science, King Saud 
University, Riyadh, Saudi Arabia.
(5)Department of Food Science, Faculty of Agricultural and Food Sciences, Laval 
University, Quebec, QC, Canada.
(6)Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, 
Ibn Zohr University, Laayoune, Morocco.

Flavonoids demonstrate beneficial effects on human health because flavonoids 
contain important biological properties. Kaempferol is a flavonol, type of 
flavonoid found in eatable plants and in plants usually employed in ancient 
drugs (Moringa oleifera, Tilia spp., fern genus spp. and gingko etc.). Some 
medicinal studies have shown that the use of foods full of kaempferol decreases 
the risk of many (cancer, vascular) diseases. All the data of 50 kaempferol 
derivatives were collected from PubChem database. Through Schrödinger software, 
3D-QSAR study was performed for 50 compounds by using method of field base. 
Conformer of kaempferol derivatives was docked against anti-diabetic, 
anti-microbial co-crystal structures and protein. To monitor the best 
anti-diabetic and antibacterial agent, particular kaempferol derivatives were 
downloaded from PubChem database. Virtual screening by molecular docking 
provided four lead compounds with four different proteins. These hit compounds 
were found to be potent inhibitor for diabetic enzymes alpha-amylase and DPP IV 
and had the potential to suppress DNA gyrase and dihydrofolate reductase 
synthesis. Molecular dynamic simulation of docked complexes evaluates the value 
of root mean square fluctuation by iMOD server. Kaempferol 3-O-alpha-L-(2, 
3-di-Z-p-coumaroyl) rhamnoside (42) compound used as anti-diabetic and 
kaempferol 3-O-gentiobioside (3) as antibacterial with good results can be used 
for drug discovery.Communicated by Ramaswamy H. Sarma.

DOI: 10.1080/07391102.2024.2308773
PMID: 38334277


2. Sci Rep. 2021 Nov 23;11(1):22796. doi: 10.1038/s41598-021-02266-3.

An integrated method for optimized identification of effective natural 
inhibitors against SARS-CoV-2 3CLpro.

Liao Q(#)(1), Chen Z(#)(1), Tao Y(1), Zhang B(1), Wu X(1), Yang L(2), Wang Q(3), 
Wang Z(1).

Author information:
(1)Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory 
for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, 
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
(2)Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory 
for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, 
Shanghai University of Traditional Chinese Medicine, Shanghai, China. 
yl7@shutcm.edu.cn.
(3)Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory 
for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, 
Shanghai University of Traditional Chinese Medicine, Shanghai, China. 
wangqingzhong3@gmail.com.
(#)Contributed equally

The current severe situation of coronavirus disease 2019 (COVID-19) caused by 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been 
reversed and posed great threats to global health. Therefore, there is an urgent 
need to find out effective antiviral drugs. The 3-chymotrypsin-like protease 
(3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its 
essential role in the regulation of virus reproduction. Here, we report an 
improved integrated approach to identify effective 3CLpro inhibitors from 
effective Chinese herbal formulas. With this approach, we identified the 5 
natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, 
rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. 
Subsequent molecular dynamics simulation additionally revealed that these 
molecules can be tightly bound to 3CLpro and confirmed effectiveness against 
COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside 
were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, 
this optimized integrated strategy for drug screening can be utilized in the 
discovery of antiviral drugs to achieve rapid acquisition of drugs with specific 
effects on antiviral targets.

© 2021. The Author(s).

DOI: 10.1038/s41598-021-02266-3
PMCID: PMC8611036
PMID: 34815498 [Indexed for MEDLINE]

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


3. Phytochem Anal. 2022 Apr;33(3):373-385. doi: 10.1002/pca.3095. Epub 2021 Nov
8.

Comparative metabolomics analysis revealed biomarkers and distinct flavonoid 
biosynthesis regulation in Chrysanthemum mongolicum and C. rhombifolium.

Duan X(1), Zhang W(1), Li J(1), Xu H(1), Hu J(1), Zhao L(2), Ma Y(1).

Author information:
(1)College of Life and Health Sciences, Northeastern University, Shenyang, 
China.
(2)College of Life Sciences, Yangling, China.

INTRODUCTION: Chrysanthemums are traditional flowers that originated in China 
and have high ornamental, economic and medicinal value. They are widely used as 
herbal remedies and consumed as food or beverages in folk medicine. However, 
little is known about their metabolic composition.
OBJECTIVES: The aims of this work were to determine the metabolic composition of 
and natural variation among different species of Chrysanthemum and to explore 
new potential resources for drug discovery and sustainable utilisation of wild 
Chrysanthemum.
METHODS: The metabolomes of Chrysanthemum mongolicum (Ling) Tzvel. and 
Chrysanthemum rhombifolium H. Ohashi & Yonek. were compared using a widely 
targeted metabolomics approach based on liquid chromatography-tandem mass 
spectrometry (LC-MS/MS).
RESULTS: In total, 477 metabolites were identified, of which 72 showed 
significant differences in expression between C. mongolicum and C. rhombifolium, 
mainly in flavonoids, organic acids and nucleotides. The flavone and flavonol 
biosynthesis pathway showed significant enrichment among the differentially 
expressed metabolites. The contents of genkwanin, trigonelline, diosmin, 
narcissoside, 3,4-dihydroxyphenylacetic acid, linarin, N',N'-p-coumarin, 
C-hexosyl-tricetin O-pentoside, chrysoeriol, acacetin and 
kaempferol-3-O-gentiobioside were significantly different between the two 
species and represent potential biomarkers.
CONCLUSION: The types of flavonoid-related metabolites in the flavonoid 
biosynthesis pathway differed between C. mongolicum and C. rhombifolium. The 
mechanisms underlying the unique adaptations of these two species to their 
environments may involve variations in the composition and abundance of 
flavonoids, organic acids, and nucleotides. These methods are promising to 
identify functional compounds in Chrysanthemum species and can provide potential 
resources for drug discovery and the sustainable utilisation of Chrysanthemum 
plants.

© 2021 John Wiley & Sons, Ltd.

DOI: 10.1002/pca.3095
PMID: 34750870 [Indexed for MEDLINE]


4. Phytother Res. 2021 Nov;35(11):6310-6323. doi: 10.1002/ptr.7278. Epub 2021 Sep
 12.

Kaempferol 3-O-gentiobioside, an ALK5 inhibitor, affects the proliferation, 
migration, and invasion of tumor cells via blockade of the TGF-β/ALK5/Smad 
signaling pathway.

Zhang Z(1), Qiao Y(1), Yang L(2), Chen Z(1), Li T(1), Gu M(1), Li C(1), Liu 
M(1), Li R(1).

Author information:
(1)Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, 
School of Pharmacy, Anhui Medical University, Hefei, China.
(2)Department of Gynecologic Oncology, The Cancer Hospital of the University of 
Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic 
Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Overactivation of TGF-β/ALK5/Smad signaling pathway has been observed in the 
advanced stage of various human malignancies. As a key component of 
TGF-β/ALK5/Smad signaling pathway transduction, TGF-β type I receptor (also 
known as ALK5) has emerged as a promising therapeutic target for cancer 
treatment. In this study, to discover a novel ALK5 inhibitor, a commercial 
natural products library was screened using docking-based virtual screening, 
followed by luciferase reporter assay. A flavonoid glycoside kaempferol 
3-O-gentiobioside (KPF 3-O-G) was identified as a potent ALK5 inhibitor through 
directly bound to the ATP-site of ALK5, resulting in the inhibitory effects on 
phosphorylation and translocation of Smad2 and expression of Smad4. 
Additionally, we found that KPF 3-O-G reduced cell proliferation and inhibited 
TGF-β-induced cell migration and invasion. Moreover, western blotting and 
immunofluorescent analysis showed that KPF 3-O-G significantly reversed the 
TGF-β-induced EMT biomarkers, including upregulation of E-cadherin and 
downregulation of N-cadherin, vimentin, and snail. In vivo study showed that KPF 
3-O-G administration reduced tumor growth in human ovarian cancer xenograft 
mouse model, without obvious toxic effect. This study provided novel insight 
into the anticancer effects of KPF-3-O-G and indicated that KPF-3-O-G might be 
developed as potential therapeutics for cancer treatment after further 
validation.

© 2021 John Wiley & Sons Ltd.

DOI: 10.1002/ptr.7278
PMID: 34514657 [Indexed for MEDLINE]


5. J Ethnopharmacol. 2016 May 26;184:58-71. doi: 10.1016/j.jep.2016.02.034. Epub 
2016 Feb 27.

Medicinal plants used in the traditional management of diabetes and its sequelae 
in Central America: A review.

Giovannini P(1), Howes MJ(2), Edwards SE(3).

Author information:
(1)Natural Capital and Plant Health Department, Royal Botanic Gardens Kew, 
Wakehurst Place, Ardingly, West Sussex RH17 6TN, United Kingdom; Centre for 
Biocultural Diversity, School of Anthropology and Conservation, Marlowe 
Building, University of Kent, Canterbury, Kent CT2 7NR, United Kingdom. 
Electronic address: peter.giovannini@gmail.com.
(2)Natural Capital and Plant Health Department, Jodrell Laboratory, Royal 
Botanic Gardens Kew, Richmond, Surrey TW9 3AB, United Kingdom; Institute of 
Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins 
Building, King's College London, 150 Stamford Street, London SE1 9NH, United 
Kingdom.
(3)Medicinal Plant Name Services, Royal Botanic Gardens Kew, Richmond, Surrey 
TW9 3 AB, United Kingdom; Center for Pharmacognosy & Phytotherapy, UCL School of 
Pharmacy, Univ. London, 29 - 39 Brunswick Sq., London WC1N 1AX, United Kingdom.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally 387 million people currently have 
diabetes and it is projected that this condition will be the 7th leading cause 
of death worldwide by 2030. As of 2012, its total prevalence in Central America 
(8.5%) was greater than the prevalence in most Latin American countries and the 
population of this region widely use herbal medicine. The aim of this study is 
to review the medicinal plants used to treat diabetes and its sequelae in seven 
Central American countries: Belize, Costa Rica, El Salvador, Guatemala, 
Honduras, Nicaragua and Panama.
MATERIALS AND METHODS: We conducted a literature review and extracted from 
primary sources the plant use reports in traditional remedies that matched one 
of the following disease categories: diabetes mellitus, kidney disease, urinary 
problems, skin diseases and infections, cardiovascular disease, sexual 
dysfunctions, visual loss, and nerve damage. Use reports were entered in a 
database and data were analysed in terms of the highest number of use reports 
for diabetes management and for the different sequelae. We also examined the 
scientific evidence that might support the local uses of the most reported 
species.
RESULTS: Out of 535 identified species used to manage diabetes and its sequelae, 
104 species are used to manage diabetes and we found in vitro and in vivo 
preclinical experimental evidence of hypoglycaemic effect for 16 of the 20 
species reported by at least two sources. However, only seven of these species 
are reported in more than 3 studies: Momordica charantia L., Neurolaena lobata 
(L.) R. Br. ex Cass., Tecoma stans (L.) Juss. ex Kunth, Persea americana Mill., 
Psidium guajava L., Anacardium occidentale L. and Hamelia patens Jacq. Several 
of the species that are used to manage diabetes in Central America are also used 
to treat conditions that may arise as its consequence such as kidney disease, 
urinary problems and skin conditions.
CONCLUSION: This review provides an overview of the medicinal plants used to 
manage diabetes and its sequelae in Central America and of the current 
scientific knowledge that might explain their traditional use. In Central 
America a large number of medicinal plants are used to treat this condition and 
its sequelae, although relatively few species are widely used across the region. 
For the species used to manage diabetes, there is variation in the availability 
and quality of pharmacological, chemical and clinical studies to explain 
traditional use.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.jep.2016.02.034
PMID: 26924564 [Indexed for MEDLINE]