Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Phytomedicine. 2024 Oct 10;135:156134. doi: 10.1016/j.phymed.2024.156134.
Online  ahead of print.

Effects of Rhaponticum carthamoides (Willd.) Iljin on endothelial dysfunction 
and the inflammatory response in type 2 diabetes mellitus mice.

Nan G(1), Wang B(2), Lv X(3), Wang W(4), Luo Z(1), Yang G(1), Ding R(5), Wang 
J(5), Lin R(6), Wang H(7).

Author information:
(1)School of Pharmacy, Xi'an Jiaotong University Health Science Center, Xi'an, 
710061, Shaanxi, PR China.
(2)Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
University Health Science Center, Xi'an, 710061, Shaanxi, PR China.
(3)Department of Pharmacy, Xi'an No.3 Hospital, the Affiliated Hospital of 
Northwest University, Xi'an, Shaanxi, PR China.
(4)Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, 
Xi'an, 710061, Shaanxi, PR China.
(5)Xinjiang Rongcheng Hake Pharmaceutical Co. Ltd, Altay region, 836500, 
Xinjiang, PR China.
(6)Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
University Health Science Center, Xi'an, 710061, Shaanxi, PR China. Electronic 
address: linrong@xjtu.edu.cn.
(7)Department of Cardiovascular Surgery, the First Affiliated Hospital of Xi'an 
Jiaotong University, Xi'an, 710061, Shaanxi, PR China. Electronic address: 
whccvsdc@126.com.

BACKGROUND: Diabetes mellitus (DM) and its complications seriously threaten 
human life and health. Rhaponticum carthamoides (Willd.) Iljin (RC) is widely 
used to treat cardiovascular diseases. Previous studies reported that RC reduces 
blood glucose levels in rats with type 1 DM. However, the effects of RC on type 
2 diabetes and vascular complications, as well as its related active components 
and underlying mechanisms, remain unclear.
PURPOSE: This study aimed to investigate the effects of RC on endothelial 
dysfunction and the inflammatory response in type 2 DM mice and to explore its 
underlying mechanism and active ingredients.
STUDY DESIGN/METHODS: Male C57BL/6J mice were used to establish a type 2 DM 
mouse model. After 12 weeks of oral administration of RC extract (60, 120, and 
240 mg/kg) to mice, blood glucose and lipid levels were assessed. The 
morphological structures of the liver and kidney tissues were observed using 
hematoxylin and eosin (HE) staining, and their functions were evaluated by 
detecting relevant biochemical indicators in the serum. Then, aorta morphology 
was observed via HE staining. In addition, serum levels of markers of 
endothelial function and inflammatory factors were detected, and the expression 
of inflammatory factors and the phosphorylation levels of key proteins in the 
aorta were examined. Furthermore, prediction and enrichment analyses of 
potential targets of RC acting on diabetic vascular lesions were performed on 
the basis of pharmacophore matching using various databases. Then, the 
expression, localization and phosphorylation levels of potential targets in the 
aortas of DM mice treated with RC were assessed using Western blotting, 
immunofluorescence, and RT‒PCR. Finally, the active components of RC were 
identified through virtual screening, and their ability to improve endothelial 
cell dysfunction was verified.
RESULTS: RC reduced blood glucose levels and serum lipid levels of total 
triglyceride (TG), total cholesterol (TC), and low density lipoprotein 
cholesterol (LDL-c), increased high density lipoprotein cholesterol (HDL-c) 
levels, and improved liver and kidney function in type 2 DM mice. RC decreased 
endothelial cell shedding in the aortas of type 2 DM mice, increased serum 
nitric oxide (NO) and nitric oxide synthase (NOS) levels, and reduced soluble 
cluster of differentiation 40 ligand (sCD40L), tumor necrosis factor α (TNF-α), 
and interleukin-1β (IL-1β) levels. Further findings indicated that RC reduced 
the expression of aortic inflammatory factors, namely, CD40, CD40L, IL-1β, and 
interleukin-6 (IL-6), and increased endothelial NOS (eNOS) phosphorylation 
levels. Sirtuin 6 (SIRT6), protein kinase B (AKT), and eNOS were predicted to be 
key node targets of RC acting on DM vascular lesions, and it was confirmed that 
RC increased SIRT6 expression and AKT phosphorylation levels in aortic 
endothelial cells. 20-Hydroxyecdysone (20E), daucosterol (Dau), euscaphic acid 
(Eus), and syringin (Syr) were identified as active components of RC. These 
components protect against TNF-α-induced human umbilical vein endothelial cell 
(HUVEC) damage and decrease the release of lactate dehydrogenase (LDH) and IL-1β 
and increased the release of NO in TNF-α-induced HUVECs in a dose-dependent 
manner.
CONCLUSION: RC reduced blood glucose and lipid levels in mice with type 2 DM and 
protected liver and kidney function. RC promotes SIRT6 expression in endothelial 
cells; upregulates the NO/NOS system by increasing AKT/eNOS phosphorylation 
levels to regulate vascular tone factors; and reduces the levels of inflammatory 
factors such as CD40, TNF-α, and IL-1β to inhibit endothelial inflammatory 
responses. Based on these mechanisms, RC improves endothelial dysfunction.

Copyright © 2024 Elsevier GmbH. All rights reserved.

DOI: 10.1016/j.phymed.2024.156134
PMID: 39418973

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.


2. Heliyon. 2024 Sep 24;10(19):e38379. doi: 10.1016/j.heliyon.2024.e38379. 
eCollection 2024 Oct 15.

Daucosterol alleviates heart failure with preserved ejection fraction through 
activating PPARα pathway.

Zhou J(1), Wang B(2), Wang M(1), Zha Y(1), Lu S(1), Zhang F(1), Peng Y(1), Duan 
Y(3), Zhong D(2), Zhang S(1).

Author information:
(1)Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui 
Higher Education Institutes, College of Food and Biological Engineering, Hefei 
University of Technology, Hefei, China.
(2)Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
(3)Department of Cardiology, The First Affiliated Hospital of University of 
Science and Technology of China, Hefei, China.

Heart failure with preserved ejection fraction (HFpEF) has been increasing in 
the population in recent years and is mainly characterized by preserved left 
ventricle ejection fraction (LVEF), diastolic dysfunction and systemic 
inflammation. Daucosterol (DAU), a glycoside of β-sitosterol, has good 
anti-inflammatory and antioxidative properties; however, its effects and 
mechanisms in HFpEF have not been investigated. To detect whether DAU could 
alleviate HFpEF, C57BL/6J male mice were fed with N-nitro-l-arginine methyl 
ester (L-NAME) in drinking water and high fat diet (HFD) and treated with DAU by 
gavage (i.g.) for 10 weeks. The results showed that DAU treatment significantly 
alleviated HFpEF in mice. Mechanistically, by controlling PPARα and preventing 
NF-κB phosphorylation, DAU reduced oxidative stress and the inflammatory 
response. In conclusion, our study provides a new clue for natural product DAU 
in alleviating HFpEF.

© 2024 Published by Elsevier Ltd.

DOI: 10.1016/j.heliyon.2024.e38379
PMCID: PMC11481624
PMID: 39416818

Conflict of interest statement: The authors declare the following financial 
interests/personal relationships which may be considered as potential competing 
interests:Shuang Zhang reports financial support was provided by 
10.13039/501100001809National Natural Science Foundation of China. Shuang Zhang 
reports financial support was provided by 10.13039/501100003995Anhui Provincial 
Natural Science Foundation. Shuang Zhang reports financial support was provided 
by Fundamental Research Funds for the Central Universities 
(10.13039/501100013773Hefei University of Technology). Yajun DUAN has patent 
#CN116036107B licensed to The First Affiliated Hospital of USTC (Anhui 
Provincial Hospital). If there are other authors, they declare that they have no 
known competing financial interests or personal relationships that could have 
appeared to influence the work reported in this paper.


3. Heliyon. 2024 Sep 26;10(19):e38541. doi: 10.1016/j.heliyon.2024.e38541. 
eCollection 2024 Oct 15.

Unveiling the therapeutic potential of Canavalia rosea leaves: Exploring 
antioxidant, anti-inflammatory, anti-arthritic, and cytotoxic activities through 
biological and molecular docking evaluation with DFT analysis.

Sazzad N(1), Fahad FI(1), Sakib SA(1), Tayab MA(1), Hanif MA(1), Reza ASMA(1), 
Islam MN(1)(2), Capasso R(3).

Author information:
(1)Department of Pharmacy, International Islamic University Chittagong, 
Chittagong, 4318, Bangladesh.
(2)Department of Pharmacy, Jahangirnagar University, Savar, Dhaka 1342, 
Bangladesh.
(3)Department of Agricultural Sciences, University of Naples Federico II, 80055, 
Portici, Naples, Italy.

BACKGROUND: Canavalia rosea is a common tropical seacoast flowering plant from 
the family of Fabaceae which is reported as bay bean and coastal jack bean; has 
a wide range of therapeutic and nutraceutical properties.
AIM: The present research aims to explore some pharmacological insights of the 
methanol extract C. rosea of leaves (MECR) and its chloroform fraction (CFCR) 
and n-hexane fraction (NFCR) through in-vitro and in-silico approaches.
METHODS: Different fractions of C. rosea were subjected to ferric reduction 
assay and total phenolic and flavonoid content assay to explore their 
antioxidant potential. The anti-inflammatory activity was assessed on the 
hypotonic-induced human erythrocyte-lysis model, while the protein denaturation 
method was applied for screening anti-arthritis properties of plant extract; and 
the cytotoxic activity was evaluated by brine shrimp lethality bioassay. In the 
in-silico study, molecular docking, pass prediction and ADME/T, analysis was 
used to investigate anti-arthritic, anti-inflammatory, antioxidant and cytotoxic 
potency of five selected compounds of C. rosea. Finally, the quantum chemical 
density functional test analysis was applied to investigate the chemical and 
physical properties of those compounds.
RESULTS: All the soluble organic extracts of C. rosea demonstrated moderate 
toxicity with strong antioxidants potential, in which MECR manifested the peak 
level of scavenging activity (2.49) on ferric reduction assay. MECR, CFCR & NFCR 
significantly protected lysis of human erythrocyte membrane induced by hypotonic 
solution, whereas MECR and CFCR were exhibited partially equal inhibitory 
activity. The in-vitro anti-arthritis assay, MECR, NFCR and CFCR showed strongly 
significant (p˂0.001) inhibitory potency at 500 μg/mL & 1000 μg/mL 
concentrations. The molecular docking simulations revealed strong binding of all 
compounds to specific receptors, with Rutin showing the highest biological 
reactivity followed by Daucosterol, β-Sitosterol, Stigmasterol, and Guanidine. 
All the compounds showed favorable reactivity patterns, with O and H atoms 
poised for nucleophilic and electrophilic attacks in chemical density functional 
calculations.
CONCLUSION: The recent investigation suggests that C. rosea could have the 
potential source of antioxidant, anti-inflammatory, anti-arthritis and cytotoxic 
activity, prompting further investigation into their mechanisms.

© 2024 The Authors.

DOI: 10.1016/j.heliyon.2024.e38541
PMCID: PMC11471479
PMID: 39403519

Conflict of interest statement: 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. Heliyon. 2024 Aug 8;10(16):e35971. doi: 10.1016/j.heliyon.2024.e35971. 
eCollection 2024 Aug 30.

Exploring the mechanism of action of Vanda tessellata extract for the treatment 
of osteoarthritis through network pharmacology, molecular modelling and 
experimental assays.

Padhee S(1), Mohanty D(1), Sahoo A(1), Jena S(1), Chandra Panda P(1), Ray A(1), 
Nayak S(1).

Author information:
(1)Centre for Biotechnology, Siksha O Anusandhan (Deemed to be University), 
Kalinganagar, Ghatikia, Bhubaneswar, India.

The present study employed a comprehensive approach of network pharmacology, 
molecular dynamic simulation and in-vitro assays to investigate the underlying 
mechanism of the anti-osteoarthritic potential of Vanda tessellata extract 
(VTE). Thirteen active compounds of VTE were retrieved from the literature and 
the Vivek-Ananth, R. P., Mohanraj, K., Sahoo, A. K., & Samal, A. (2023). IMPPAT 2.0: An Enhanced and Expanded Phytochemical Atlas of Indian Medicinal Plants. ACS omega, 8(9), 8827–8845. https://doi.org/10.1021/acsomega.3c00156 database. All of these passed the drug likeness and oral 
bioavailability parameters. A total of 535 VTE targets and 2577 osteoarthritis 
related targets were obtained. The compound-target-disease network analysis 
revealed vanillin, daucosterol, gigantol and syringaldehyde as the core key 
components. Protein-protein interaction analysis revealed BCL2, FGF2, ICAM 1, 
MAPK1, MMP1, MMP2, MMP9, COX2, STAT3 and ESR1 as the hub genes. Kyoto 
Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed AGE-RAGE 
signalling pathway, HIF-1 signalling pathway and ESR signalling pathway as the 
major signalling pathway of VTE involved in treating osteoarthritis. Molecular 
docking analysis showed daucosterol and gigantol to have good binding affinity 
with BCL2, ESR1 and MMP9, and the results were further confirmed through 
molecular dynamics simulation analysis. The mechanism predicted by network 
pharmacology was validated in vitro on IL-1β-induced SW982 synovial cells. VTE 
did not show any cytotoxicity and inhibited the migration of SW982 cells. VTE 
inhibited the expression level of IL-6, IL-8, TNF-α, PGE-2, MMP-2 and MMP-9 in a 
dose-dependent manner. VTE inhibited nuclear translocation of NF- κβ and 
suppressed phosphorylation of p38, extracellular signal-regulated kinase (ERK), 
and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase 
(MAPK) signalling pathway. The results showed that VTE exerted an 
anti-osteoarthritic effect by a multi-target, multi-component and 
multi-signalling pathway approach.

© 2024 The Authors.

DOI: 10.1016/j.heliyon.2024.e35971
PMCID: PMC11367146
PMID: 39224251

Conflict of interest statement: 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. Cell Biochem Biophys. 2024 Aug 31. doi: 10.1007/s12013-024-01486-4. Online
ahead  of print.

Investigation of Cissus populnea as a Potential Therapeutic Agent for Erectile 
Dysfunction.

Akinjiyan MO(1)(2), Elekofehinti OO(3)(4), Oluwatuyi AO(3)(4), Nwanna EE(5), 
Lawal AO(3).

Author information:
(1)Bioinformatics and Molecular Biology Unit, Department of Biochemistry, 
Federal University of Technology, Akure, Ondo State, Nigeria. 
moakinjiyan@futa.edu.ng.
(2)Teady Bioscience Research Laboratory, Akure, Ondo State, Nigeria. 
moakinjiyan@futa.edu.ng.
(3)Bioinformatics and Molecular Biology Unit, Department of Biochemistry, 
Federal University of Technology, Akure, Ondo State, Nigeria.
(4)Teady Bioscience Research Laboratory, Akure, Ondo State, Nigeria.
(5)Functional foods and Nutrigenomics unit, Department of Biochemistry, Federal 
University of Technology, Akure, Ondo State, Nigeria.

Cissus populnea (CP) is a plant reported to possess an erection-enhancing 
ability, though mechanisms remain unclear. Drugs targeting phosphodiesterase 5 
(PDE5) inhibition, such as sildenafil, have been employed to treat erectile 
dysfunction (EDRF), but they are associated with several complications. This 
study investigated the effect of C. populnea extracts (aqueous and saponin-rich) 
on the activity and gene expressions of proteins related to erection. PDE5, 
Nitric oxide synthase (NOS) and androgen receptor (AR) genes were studied using 
RT-PCR on CP-treated paroxetine-induced ERDF-rats. It also employed Schrödinger 
suites for investigations such as molecular and induced-fit docking, MMGBSA, 
ADMET, and QSAR profiling of CP-phytocompounds. C. populnea extracts reduce the 
activity and downregulate the expression of the PDE5 gene while upregulating the 
expressions of AR and NOS genes in the ERDF-rats relative to the control group. 
Five (leading) compounds with induced-fit docking (IFD) scores in kcal/mol, 
namely, stigmasterol (-638.73), daucosterol (-644.73), furostanol (-639.29), 
papaverine (-639.03), and capsaicin (-642.88), had better docking scores of 
-9.936, -9.824, -9.064, -8.863, and -8.736 kcal/mol, respectively, compared with 
those of sildenafil (-8.611 kcal/mol). They also showed an excellent ADMET 
profile, satisfying Lipinski's rule of five. The MMGBSA predictions revealed 
that stigmasterol, daucosterol, papaverine, and capsaicin had binding free 
energies of -45.29, -59.14, -50.63, and -50.47 kcal/mol, respectively, 
suggesting that they are significant inhibitors of PDE5. The QSAR model revealed 
that lead compounds possess good pIC50 values. These results indicate that C. 
populnea is a more promising possible treatment for controlling EDRF and 
deserves further research.

© 2024. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s12013-024-01486-4
PMID: 39217270