Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. PLoS One. 2024 Mar 29;19(3):e0301348. doi: 10.1371/journal.pone.0301348. 
eCollection 2024.

From Flora to Pharmaceuticals: 100 new additions to angiosperms of Gafargaon 
subdistrict in Bangladesh and unraveling antidiabetic drug candidates targeting 
DPP4 through in silico approach.

Ahmed SS(1), Rahman MO(1).

Author information:
(1)Department of Botany, Faculty of Biological Sciences, University of Dhaka, 
Dhaka, Bangladesh.

Addition to the angiosperm flora provides essential insights into the 
biodiversity of a region, contributing to ecological understanding and 
conservation planning. Gafargaon subdistrict under Mymensingh district in 
Bangladesh represents a diverse population of angiosperms with a multifaceted 
ecosystem that demands re-evaluation of the existing angiosperm diversity of 
Gafargaon to update the status of angiosperm taxa and facilitate their 
conservation efforts. With this endeavor, a total of 100 angiosperm taxa 
belonging to 90 genera and 46 families were uncovered as additional occurrence 
in Gafargaon. The species in the area showcased a variety of life forms, 
including 63 herbs, 14 shrubs, 14 trees, and 9 climbers. Among the recorded 
taxa, Chamaecostus cuspidatus (Nees & Mart.) C.D. Specht & D.W. Stev. was 
selected for antidiabetic drug design endeavor based on citation frequency and 
ethnomedicinal evidence. A total of 41 phytochemicals of C. cuspidatus were 
screened virtually, targeting the Dipeptidyl peptidase 4 protein through 
structure-based drug design approach, which unveiled two lead compounds, such as 
Tigogenin (-9.0 kcal/mol) and Diosgenin (-8.5 kcal/mol). The lead candidates 
demonstrated favorable pharmacokinetic and pharmacodynamic properties with no 
major side effects. Molecular dynamics simulation revealed notable stability and 
structural compactness of the lead compounds. Principal component analysis and 
Gibbs free energy landscape further supported the results of molecular dynamics 
simulation. Molecular mechanics-based MM/GBSA approach unraveled higher free 
binding energies of Diosgenin (-47.36 kcal/mol) and Tigogenin (-46.70 kcal/mol) 
over Alogliptin (-46.32 kcal/mol). The outcome of the present investigation 
would enrich angiosperm flora of Gafargaon and shed light on the role of C. 
cuspidatus to develop novel antidiabetic therapeutics to combat diabetes.

Copyright: © 2024 Ahmed, Rahman. This is an open access article distributed 
under the terms of the Creative Commons Attribution License, which permits 
unrestricted use, distribution, and reproduction in any medium, provided the 
original author and source are credited.

DOI: 10.1371/journal.pone.0301348
PMCID: PMC10980240
PMID: 38551991 [Indexed for MEDLINE]

Conflict of interest statement: The authors have declared that no competing 
interests exist.


2. Org Biomol Chem. 2024 Mar 6;22(10):2081-2090. doi: 10.1039/d3ob02101g.

Total synthesis and cytotoxicity evaluation of the spirostanol saponin gitonin.

Li Y(1)(2), Lv X(3), Liu J(1)(2)(4), Du Y(1)(2)(4).

Author information:
(1)State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research 
Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 
100085, China. junliu@rcees.ac.cn.
(2)School of Chemistry and Chemical Engineering, University of Chinese Academy 
of Sciences, Beijing 100049, China.
(3)CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
(4)Binzhou Institute of Technology, Weiqiao-UCAS Science and Technology Park, 
Binzhou 256606, Shandong Province, China.

The spirostanol saponin gitonin was efficiently synthesized in 12 steps (longest 
linear sequence) in 18.5% overall yield from the commercially available 
isopropyl β-D-1-thiogalactopyranoside (IPTG) and tigogenin. A cascade two-step 
glycosylation and Schmidt's inverse procedure significantly facilitated the 
synthesis of gitonin and its derivatives. The cytotoxic activities of gitonin 
and its structural analogues were evaluated against A549, HepG2, and MCF-7, and 
most of them exhibited moderate to excellent inhibitory activity. Our study 
demonstrates that the removal of the β-D-galactopyranosyl residue (attached at 
C-2 of the glucose unit) from gitonin would not decrease the inhibition 
activities; however, further cleavage of sugar units could seriously reduce the 
activities. A bioassay on these cancer cell lines also suggested that the 
presence of 2α-hydroxy on the aglycone weakened the cytotoxicity of the designed 
saponin.

DOI: 10.1039/d3ob02101g
PMID: 38363172 [Indexed for MEDLINE]


3. J Biomol Struct Dyn. 2024 Jan 4:1-22. doi: 10.1080/07391102.2023.2299743.
Online  ahead of print.

Natural sapogenins as potential inhibitors of aquaporins for targeted cancer 
therapy: computational insights into binding and inhibition mechanism.

Alotaibi MO(1), Alotaibi NM(1), Alwaili MA(1), Alshammari N(2), Adnan M(2), 
Patel M(3).

Author information:
(1)Department of Biology, College of Science, Princess Nourah bint Abdulrahman 
University, Riyadh, Saudi Arabia.
(2)Department of Biology, College of Science, University of Ha'il, Ha'il, Saudi 
Arabia.
(3)Research and Development Cell, Department of Biotechnology, Parul Institute 
of Applied Sciences, Parul University, Vadodara, India.

Aquaporins (AQPs) are membrane proteins that facilitate the transport of water 
and other small molecules across biological membranes. AQPs are involved in 
various physiological processes and pathological conditions, including cancer, 
making them as potential targets for anticancer therapy. However, the 
development of selective and effective inhibitors of AQPs remains a challenge. 
In this study, we explored the possibility of using natural sapogenins, a class 
of plant-derived aglycones of saponins with diverse biological activities, as 
potential inhibitors of AQPs. We performed molecular docking, dynamics 
simulation and binding energy calculation to investigate the binding and 
inhibition mechanism of 19 sapogenins against 13 AQPs (AQP0-AQP13) that are 
overexpressed in various cancers. Our results showed that out of 19 sapogenins, 
8 (Diosgenin, Gitogenin, Tigogenin, Ruscogenin, Yamogenin, Hecogenin, 
Sarsasapogenin and Smilagenin) exhibited acceptable drug-like characteristics. 
These sapogenin also exhibited favourable binding affinities in the range of 
-7.6 to -13.4 kcal/mol, and interactions within the AQP binding sites. 
Furthermore, MD simulations provided insights into stability and dynamics of the 
sapogenin-AQP complexes. Most of the fluctuations in binding pocket were 
observed for AQP0-Gitogenin and AQP4-Diosgenin. However, remaining 
protein-ligand complex showed stable root mean square deviation (RMSD) plots, 
strong hydrogen bonding interactions, stable solvent-accessible surface area 
(SASA) values and minimum distance to the receptor. These observations suggest 
that natural sapogenin hold promise as novel inhibitors of AQPs, offering a 
basis for the development of innovative therapeutic agents for cancer treatment. 
However, further validation of the identified compounds through experiments is 
essential for translating these findings into therapeutic 
applications.Communicated by Ramaswamy H. Sarma.

DOI: 10.1080/07391102.2023.2299743
PMID: 38174738


4. Int J Mol Sci. 2023 Jul 14;24(14):11487. doi: 10.3390/ijms241411487.

6-Oxofurostane and (iso)Spirostane Types of Saponins in Smilax sieboldii: 
UHPLC-QToF-MS/MS and GNPS-Molecular Networking Approach for the Rapid 
Dereplication and Biodistribution of Specialized Metabolites.

Avula B(1), Bae JY(1), Ahn J(1), Katragunta K(1), Wang YH(1), Wang M(1), Kwon 
Y(1), Khan IA(1)(2), Chittiboyina AG(1).

Author information:
(1)National Center for Natural Products Research, School of Pharmacy, University 
of Mississippi, University, MS 38677, USA.
(2)Division of Pharmacognosy, Department of BioMolecular Sciences, School of 
Pharmacy, University of Mississippi, University, MS 38677, USA.

Identifying novel phytochemical secondary metabolites following classical 
pharmacognostic investigations is tedious and often involves repetitive 
chromatographic efforts. During the past decade, Ultra-High Performance Liquid 
Chromatography-Quadrupole Time of Flight-Tandem Mass Spectrometry 
(UHPLC-QToF-MS/MS), in combination with molecular networking, has been 
successfully demonstrated for the rapid dereplication of novel natural products 
in complex mixtures. As a logical application of such innovative tools in 
botanical research, more than 40 unique 3-oxy-, 3, 6-dioxy-, and 3, 6, 
27-trioxy-steroidal saponins were identified in aerial parts and rhizomes of 
botanically verified Smilax sieboldii. Tandem mass diagnostic fragmentation 
patterns of aglycones, diosgenin, sarsasapogenin/tigogenin, or laxogenin were 
critical to establishing the unique nodes belonging to six groups of nineteen 
unknown steroidal saponins identified in S. sieboldii. Mass fragmentation 
analysis resulted in the identification of 6-hydroxy sapogenins, believed to be 
key precursors in the biogenesis of characteristic smilaxins and sieboldins, 
along with other saponins identified within S. sieboldii. These analytes' 
relative biodistribution and characteristic molecular networking profiles were 
established by analyzing the leaf, stem, and root/rhizome of S. sieboldii. 
Deducing such profiles is anticipated to aid the overall product integrity of 
botanical dietary supplements while avoiding tedious pharmacognostic 
investigations and helping identify exogenous components within the finished 
products.

DOI: 10.3390/ijms241411487
PMCID: PMC10380369
PMID: 37511246 [Indexed for MEDLINE]

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


5. Nat Prod Res. 2023 Nov-Dec;37(24):4239-4243. doi:
10.1080/14786419.2023.2174538.  Epub 2023 Feb 16.

The interaction of anti-inflammatory and anti-tumor components in the 
traditional Chinese medicine Solanum lyratum Thunb.

Zou D(1)(2)(3), Li X(4), Zhou X(1)(2)(3), Luo B(1)(2)(3), Faruque MO(5), Hu 
S(6), Chen J(6), Hu X(1)(2)(3).

Author information:
(1)Intitute of Medicinal Plants, College of Plant Science and Technology, 
Huazhong Agricultural University, Wuhan, China.
(2)National & Local Joint Engineering Research Center for Medicinal Plant 
Breeding and Cultivation, Wuhan, China.
(3)Hubei Provincial Engineering Research Center for Medicinal Plants, Wuhan, 
China.
(4)College of Life Science and technology, Wuhan Polytechnic University, Wuhan, 
China.
(5)Ethnobotany and Pharmacognosy Lab, Department of Botany, University of 
Chittagong, Chattogram, Bangladesh.
(6)Department of Head and Neck Surgery, Hubei Cancer Hospital, Tongji Medical 
College, Huazhong University of Science and Technology, Wuhan, China.

Solanum lyratum Thunb is a traditional Chinese medicinal with a significant 
clinical outcome for tumor treatment; however, chemicals or fractions separated 
from the herb did not exhibit strong and comparable efficacy. To investigate the 
potential synergy or antagonism among chemicals in the extract, we obtained the 
compounds solavetivone (SO), tigogenin (TI) and friedelin (FR) from the herb. 
The anti-tumor effects of these three monomer compounds alone or in combination 
with the anti-inflammatory compound DRG were also tested in this study. SO, FR 
and TI used alone did not inhibit the proliferation of A549 and HepG2 cells, but 
the combination of the three achieved 40% inhibition. In vitro anti-inflammatory 
analysis showed that DRG had a stronger anti-inflammatory effect than TS at the 
same concentration, and the combination of DRG with SO, FR or TI inhibited the 
anti-tumor effect of DRG. This is the first study that documented the 
synergistic and antagonistic interactions between different compounds in a 
single herb.

DOI: 10.1080/14786419.2023.2174538
PMID: 36794855 [Indexed for MEDLINE]