Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Anticancer Agents Med Chem. 2024 Oct 29. doi: 
10.2174/0118715206340868241018075528. Online ahead of print.

In vivo, In vitro, and In silico Studies of Umbelliferone and Irinotecan on 
MDA-MB-231 Breast Cancer Cell Line and Drosophila melanogaster Larvae.

Tamtürk E(1), Yalcin S(2), Ercan F(3), Tunçbilek A(1).

Author information:
(1)Department of Biology, Faculty of Art and Sciences, Erciyes University, 
38100, Kayseri, TÜRKİYE.
(2)Department of Medical Pharmacology, Faculty of Medicine, Kırşehir Ahi Evran 
University, 40100, Kırşehir, TÜRKİYE.
(3)Department of Plant Protection, Faculty of Agriculture, Kırşehir Ahi Evran 
University, 40100, Kırşehir, TÜRKİYE.

AIMS: Deaths from cancer are still very common all over the world and continue 
to be the focus of scientific research. Chemotherapy is one of the primary 
treatments used to prevent deaths from cancer. Side effects of chemotherapeutic 
drugs and resistance of cells to drugs are essential problems that limit the 
treatment process. Drug combination therapy is regarded as a significant 
application that inhibits the growth of tumors and is anticipated to provide a 
solution for the issues encountered. The combination therapy aims at a 
synergistic effect that will limit drug resistance and cytotoxic effects with 
appropriate drug combinations. In this context, we aim to investigate the in 
vitro, in vivo, and in silico effects of single and combined doses of 
umbelliferone and irinotecan, known for their anticarcinogenic and curative 
effects, on MDA-MB-231 breast cancer cell lines and the model organism 
Drosophila melanogaster.
BACKGROUND: Irinotecan is currently used as an anticarcinogenic drug. 
Anticarcinogenic effects of umbelliferone have also been detected. The in vivo, 
in vitro, and in silico impacts of single and combined doses use of these two 
agents are not yet available in the literature.
OBJECTIVE: This study aims to determine the anticarcinogenic effects of single 
and combined use of umbelliferone and irinotecan at the molecular level. It also 
attempts to determine the binding energies of chemicals to cancerrelated 
proteins through docking and molecular dynamic studies.
METHOD: The cytotoxic effects of individual and combinational doses of 
umbelliferone and irinotecan on the MDAMB- 231 cell line and D. melanogaster 
were calculated by XTT and probit analyses. IC50 values for the cancer cells, 
LC50, and LC99 values for D. melanogaster were found. Gene expression analysis 
was performed to determine the effects of chemical agents on miR-7, miR-11, and 
miR-14, and their expression levels were found. The sequences of miRNAs not 
found in the literature were determined, and their molecular imaging was 
performed. In addition, the binding energies of irinotecan and umbelliferone to 
Bcl-2, Bad, and Akt1 proteins, which are known to have apoptotic effects, were 
found by the molecular docking method. Molecular dynamics studies of Bad 
proteins and chemicals were also performed. The drug potential of chemicals was 
determined by ADME/T analysis.
RESULT: The cytotoxic effect on cells was calculated, and the IC50 value of 
umbelliferone was calculated as 158 μM, the IC50 value of irinotecan was 
calculated as 48,3 μM and the IC50 value was calculated as 20 μM. In the probit 
analysis performed to calculate the cytotoxic effects of drugs on D. 
melanogaster, the LC50 value of umbelliferone was 2,5 μM, and the LC99 value was 
13,4 μM. The LC50 value of irinotecan was found to be 0,1 μM, and the LC99 value 
was 0,28 μM. It was concluded that single and combined doses of chemicals in the 
invasion experiment significantly affected the spread of cells. As a result of 
expression analysis, a significant increase in HsamiR- 7 (Homo sapiens miRNA-7), 
Hsa-miR-14 (Homo sapiens miRNA-14), and Hsa-miR-11(Homo sapiens miRNA-11) 
expression was observed in cells treated with umbelliferone irinotecan compared 
to the control groups.
CONCLUSION: In our study, it can be concluded that the cytotoxic effects of 
individual and combination doses of umbelliferone and irinotecan on MDA-MB-231 
cells and D. melanogaster larvae are significant. In addition, the effects of 
umbelliferone and irinotecan on the expression level of miR-7, which is a common 
D. melanogaster and human miRNA, should be widely investigated. Expression 
analyses and docking studies of Hsa-miR-11 and Hsa-miR-14, which have been newly 
studied and are not in data repositories, are important for cancer research. In 
particular, the expression and binding energy of these miRNAs in new drug 
combinations and the expression level in different cancer cell lines are 
important for future studies. Another crucial point is that in vivo tests using 
different model species validate the usage of drugs at both single and mixed 
dosages. Other: As a result of this study, the in vivo, in vitro, and in silico 
effects of single and combined doses of umbelliferone and irinotecan were 
determined. In future studies, it would be useful to determine the binding 
energies of umbelliferone and irinotecan to other cancer-related proteins and to 
find their interactions with different miRNAs. Additionally, studies on 
different model organisms are also important.

Copyright© Bentham Science Publishers; For any queries, please email at 
epub@benthamscience.net.

DOI: 10.2174/0118715206340868241018075528
PMID: 39473207


2. J Agric Food Chem. 2024 Oct 30;72(43):23832-23843. doi: 
10.1021/acs.jafc.4c04580. Epub 2024 Oct 21.

Peroxyl Radical Trapping Antioxidant Activity of Essential Oils and Their 
Phenolic Components.

Pan W(1), Velasco Abadia A(1), Guo Y(1), Gabbanini S(2), Baschieri A(3), Amorati 
R(1), Valgimigli L(1)(4).

Author information:
(1)Department of Chemistry "G. Ciamician", University of Bologna, Via P. Gobetti 
85, 40129 Bologna, Italy.
(2)R&D Division, BeC s.r.l., Via C. Monteverdi 49, 47122 Forlì, Italy.
(3)Institute for Organic Synthesis and Photoreactivity (ISOF), National Research 
Council of Italy (CNR), Via P. Gobetti 101, I-40129 Bologna, Italy.
(4)Tecnopolo di Rimini, Via D. Campana 71, 47922 Rimini, Italy.

Essential oils (EOs) are gaining importance as sustainable food antioxidants, 
but kinetic data on peroxyl radical trapping are missing. Thirteen EOs from 11 
botanical species were studied in the inhibited autoxidation of cumene by 
oxygen-uptake kinetics. EOs of Juniperus oxycedrus, Syzygium aromaticum, Thymus 
vulgaris, Thymbra capitata, Betula alba, Pimenta racemosa, and Satureja montana, 
containing 23-86% phenolic components by gas chromatography/mass spectrometry 
(GC-MS) analysis, afforded inhibition rate constants kinh in the order of 104 
M-1 s-1 at 30 °C similar to reference butylhydroxytoluene 
(2,6-di-tert-butyl-4-methylphenol) (BHT). They matched or outperformed BHT in 
the protection of olive oil. The EOs Daucus carota and Cedrus atlantica with <1% 
phenols and those of Apium graveolens and Tagetes minuta with no phenolics had 
no chain-breaking activity. Key components carvacrol, thymol, eugenol, 
dihydroeugenol, umbelliferone, conyferyl alcohol, o-cresol, m-cresol, p-cresol, 
4-allylphenol, 2,3-xylenol, 2,4-xylenol, and phenol had kinh in the range of 
103-104 M-1 s-1 and, along with EOs containing them, could potentially replace 
BHT in the protection of food products.

DOI: 10.1021/acs.jafc.4c04580
PMID: 39433300 [Indexed for MEDLINE]


3. Chem Biodivers. 2024 Oct 16:e202401128. doi: 10.1002/cbdv.202401128. Online 
ahead of print.

Friedericia chica, a medicinal plant from the Amazon region, is repellent 
against Aedes aegypti: in vivo and molecular docking evidence.

Miorando D(1), Maccagnan JC(2), Vecchia CAD(1), Ferraz CV(3), Monteiro M(4), 
Busato MA(4), Lutinski JA(4), Roman MI(5), de Souza Rezende R(6), Gutiérrez 
MV(7), Hage-Melim LIS(8), Pontes FMM(9), Barison A(10), Nepel A(11), Veselinova 
A(12), Roman Junior WA(13).

Author information:
(1)Unochapeco, PPGCS, Servidão Anjo da Guarda, Chapecó, 89809-900, Chapecó, 
BRAZIL.
(2)Unochapeco, PPGCS, Servidão Anjo da Guarda, 89809-900, Chapecó, BRAZIL.
(3)Unochapeco, PPGCS, Servidão Anjo da Guarda, Chapecó, Chapecó, BRAZIL.
(4)Unochapeco, PPGCS, Servidão Anjo da Guarda, Chapecó, BRAZIL.
(5)Unochapeco, Lab. Pharmacognosy, Servidão Anjo da Guarda, Chapecó, BRAZIL.
(6)Unochapeco, PPGCA, Servidão Anjo da Guarda, Chapecó, BRAZIL.
(7)Universidad de Sonora, Department of Chemical, Biological and Agricultural 
Sciences, Servidão Anjo da Guarda, Sonora, MEXICO.
(8)Federal University of Amapa, Pharmacy Course, Servidão Anjo da Guarda, 
Macapá, BRAZIL.
(9)Federal University of Amapá, Pharmacy Course, Servidão Anjo da Guarda, 
Macapá, BRAZIL.
(10)Federal University of Parana, Laboratory of RMN, Servidão Anjo da Guarda, 
Curitiba, BRAZIL.
(11)Unochapeco, Laboratory of RMN, Servidão Anjo da Guarda, Curitiba, BRAZIL.
(12)Universidad de Salamanca, Department of Physical Chemistry, Servidão Anjo da 
Guarda, Salamanca, SPAIN.
(13)Community University of Chapeco Region, PPGCS, 1330 Rua Quatorze de Agosto - 
E, casa, 89801-251, Chapecó, BRAZIL.

Fridericia chica is widely distributed in Brazil, where it is commonly known as 
crajiru or pariri in several regions. Despite its popular use for treating 
inflammations and as an insect repellent, there has been limited assessment of 
its chemical and biological properties, including its bioinsecticide activities. 
In this study, we conducted phytochemical analyses and investigated the 
larvicidal and repellent effects of F. chica against the mosquito Aedes aegypti. 
The F. chica (HEFc) hydroalcoholic extract was partitioned using column 
chromatography, and subfractions were analyzed using chromatographic and 
spectroscopic analyses (ESI-IT-MSn and NMR). In addition, HEFc was evaluated for 
its larvicidal and repellent activities. Phytochemical analyses revealed the 
presence of 17 constituents, including 2,4-dihydroxybenzoic and p-coumaric 
acids, along with umbelliferone, acetovanilone, myricetin-3-O-glucuronide, and 
cis-isorhapontigenin, which are reported for the first time in this species. 
Although no larvicidal effect was observed at the doses tested, the HEFc 
exhibited promising repellent effects against A. aegypti, which aligns with its 
ethnopharmacological potential. In addition, molecular docking studies 
demonstrated that the compounds of HEFc interacted efficiently with insect 
odorant binding proteins (OBPs), providing repellent effects. Consistent with 
the chemical profile and in silico studies, preparations of F. chica have 
considerable repellent potential.

© 2024 Wiley‐VCH GmbH.

DOI: 10.1002/cbdv.202401128
PMID: 39412496


4. J Mol Med (Berl). 2024 Oct 4. doi: 10.1007/s00109-024-02491-z. Online ahead of
 print.

Umbelliferone alleviates impaired wound healing and skin barrier dysfunction in 
high glucose-exposed dermal fibroblasts and diabetic skins.

Kim DY(1), Kang YH(2), Kang MK(3).

Author information:
(1)Department of Food Science and Nutrition, Andong National University, 1375, 
Gyeongdong-ro, Andong-si, Gyeongsangbuk-do, 36729, Republic of Korea.
(2)Department of Food and Nutrition, Hallym University, 1, Hallymdaehak-gil, 
Chuncheon-si, Gangwon-do, Republic of Korea.
(3)Department of Food Science and Nutrition, Andong National University, 1375, 
Gyeongdong-ro, Andong-si, Gyeongsangbuk-do, 36729, Republic of Korea. 
mkkang@anu.ac.kr.

Skin wound healing is a complex process involving various cellular and molecular 
events. However, chronic wounds, particularly in individuals with diabetes, 
often experience delayed wound healing, potentially leading to diabetic skin 
complications. In this study, we examined the effects of umbelliferone on skin 
wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic 
mouse model. Our results demonstrate that umbelliferone enhances several crucial 
aspects of wound healing. It increases the synthesis of key extracellular matrix 
components such as collagen I and fibronectin, as well as proteins involved in 
cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the 
secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of 
cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates 
levels of skin hydration-related proteins like HAS2 and AQP3. Notably, 
umbelliferone reduces the expression of HYAL, thereby potentially decreasing 
tissue permeability. As a result, it promotes extracellular matrix deposition, 
activates cell migration and proliferation, and stimulates pro-angiogenic 
factors while maintaining skin barrier functions. In summary, these findings 
underscore the therapeutic potential of umbelliferone in diabetic wound care, 
suggesting its promise as a treatment for diabetic skin complications. KEY 
MESSAGES: Umbelliferone suppressed the breakdown of extracellular matrix 
components in the skin dermis while promoting their synthesis. Umbelliferone 
augmented the migratory and proliferative capacities of fibroblasts. 
Umbelliferone activated the release of angiogenic factors in diabetic wounds, 
leading to accelerated wound healing. Umbelliferone bolstered intercellular 
adhesion and reinforced the skin barrier by preventing moisture loss and 
preserving skin hydration.

© 2024. The Author(s).

DOI: 10.1007/s00109-024-02491-z
PMID: 39363131


5. Sci Rep. 2024 Sep 23;14(1):21987. doi: 10.1038/s41598-024-69607-w.

Phytochemical, biological, and computational investigations of Ephedra alata 
Decne. growing in salinity conditions of Arabian Peninsula.

Mohammed HA(1), Said R(2)(3), Abbas MM(3)(4), Al-Najjar BO(2)(3), Abd-Elmoniem 
E(5), Khan RA(1), Alsohim AS(6), Almahmoud SA(1), Kedra TA(7), Shehata SM(8), 
Ismail A(9).

Author information:
(1)Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 
Qassim University, Qassim, 51452, Saudi Arabia.
(2)Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman 
University, Amman, 19328, Jordan.
(3)Pharmacological and Diagnostic Research Laboratory, Al-Ahliyya Amman 
University, Amman, 19328, Jordan.
(4)Department of Medical Laboratory Sciences, Faculty of Allied Medical 
Sciences, Al-Ahliyya Amman University, Amman, 19328, Jordan.
(5)Department of enviromental and natural resources, College of Agriculture and 
Food, Qassim University, P.O. Box 6622, Buraydah, 51452, Qassim, Saudi Arabia.
(6)Department of Plant Production, College of Agriculture and Food, Qassim 
University, P.O. Box 6622, Buraydah, 51452, Qassim, Saudi Arabia.
(7)Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, 
Al-Azhar University, Cairo, 11371, Egypt.
(8)Clinical Pathology Department, Ain Shams University Hospitals, Cairo, Egypt.
(9)Pharmacognosy Department, Faculty of Pharmacy, Fayoum University, Fayoum, 
63514, Egypt. Ahmed_ph_fut@yahoo.com.

Ephedra alata Decne is a medicinal plant widely used in traditional medicine for 
the management of bronchial asthma and cancer. Phytochemical analysis and 
biological activities, including antioxidant and anticancer effects, were 
investigated in the current work as new findings for the plant E. alata, a 
species growing wildly in the marsh and saline environments of the central area 
of Saudi Arabia. The Ultra Pressure Liquid Chromatography coupled with Electron 
spray ionization-Quadropole-Time of flight (UPLC-ESI-Q-TOF) system was used for 
the phytochemical analysis of the plant constituents. In addition, Polyphenolic 
profiling including the total phenolic (TPC) and flavonoid (TFC) contents of the 
plant extracts were measured. Phenolic acids were found at the highest relative 
percentages among all the identified compounds and were measured at 66.07 mg GAE 
(Gallic acid equivalent). The UPLC analysis of the E. alata extract indicated 
the presence of chlorogenic acid, syringic acid, caffeic acid, vanillic acid, 
rosmarinic acid, umbelliferone, isorhoifolin, and apigenin at the highest 
relative percentages. Mineral analysis indicated that the microelement content 
of E. alata was relatively low, except for magnesium (Mg). In vitro antioxidant 
assays revealed the ability of the plant to scavenge DPPH free radicals, reduced 
molybdenum ions, and ferrous at levels of 14.63, 19.97, and 27.78 mg Trolox 
equivalents, respectively. The extract induced transition metal chelation at 
31.36 mg EDTA equivalents. The extract induced cytotoxic effects against MDA-231 
and A549 cell lines at IC50 levels of 25.31 and 39.81 µg/mL, respectively. The 
plant extract inhibited the colonization and migration of cancer cells as part 
of its potential anticancer effects. In addition, major E. alata constituents 
like isorhoifolin, chlorogenic acid, apigenin, and rosmarinic acid exhibited the 
lowest binding energy to the CAIX enzyme at - 8.41, - 6.64, - 6.32, and 
- 6.26 kcal/mol, respectively, compared to the binding energy (- 7.72 kcal/mol) 
of the co-crystallized ligand (Y0R). The docking results further supported the 
selection of the CAIX enzyme as a standard predictive therapeutic target, 
since it exhibited significant binding interactions with the major constituents 
of the plant.

© 2024. The Author(s).

DOI: 10.1038/s41598-024-69607-w
PMCID: PMC11420223
PMID: 39313524 [Indexed for MEDLINE]

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