Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Toxicon. 2024 Oct 19;251:108147. doi: 10.1016/j.toxicon.2024.108147. Online 
ahead of print.

Acute oral toxicity and genotoxicity assessment of the essential oil from Croton 
pulegiodorus Baill (Euphorbiaceae) leaves in mice.

Monteiro Dos Santos PÉ(1), Cavalcanti de Barros M(1), Vieira de Barros A(1), 
Araújo RM(2), de Oliveira Marinho A(1), Arnaldo da Silva A(3), Melo de Oliveira 
MB(1), Giselly Dos Santos Souza T(4), Chagas CA(4), de Albuquerque Lima T(1), 
Leite de Siqueira Patriota L(1), Silva de Oliveira AP(1), Napoleão TH(5), Guedes 
Paiva PM(6).

Author information:
(1)Departamento de Bioquímica, Centro de Biociências, Universidade Federal de 
Pernambuco, Recife, Pernambuco, Brazil.
(2)Instituto de Química, Universidade Federal do Rio Grande do Norte, Natal, Rio 
Grande do Norte, Brazil.
(3)Departamento de Anatomia, Centro de Biociências, Universidade Federal de 
Pernambuco, Recife, Pernambuco, Brazil.
(4)Centro Acadêmico de Vitória, Universidade Federal de Pernambuco, Vitória de 
Santo Antão, Pernambuco, Brazil.
(5)Departamento de Bioquímica, Centro de Biociências, Universidade Federal de 
Pernambuco, Recife, Pernambuco, Brazil. Electronic address: 
thiago.napoleao@ufpe.br.
(6)Departamento de Bioquímica, Centro de Biociências, Universidade Federal de 
Pernambuco, Recife, Pernambuco, Brazil. Electronic address: 
patricia.paiva@ufpe.br.

Essential oils obtained from Croton pulegiodorus leaf are renowned for their 
biological activities; however, data on their toxicity are limited. Therefore, 
this study aimed to evaluate the acute oral toxicity and genotoxicity of a C. 
pulegiodorus leaf essential oil (CPLEO). Chemical characterization of CPLEO was 
conducted by gas chromatography coupled to mass spectrometry (GC-MS). In vitro 
assay was performed to verify the hemolytic capacity of the oil in mice 
erythrocytes. Next, an acute oral toxicity study was conducted on female mice at 
CPLEO doses of 2000, 1000, 500, 250, 100, and 50 mg/kg. Hematological, 
biochemical, and histopathological markers were assessed in mice from groups 
were no death occurred. Relative consumption of water and food and the weight of 
animals and their organs were also recorded. Finally, a genotoxicity analysis 
was performed using the micronucleus and comet assays. The extraction yield of 
CPLEO was 1.149% and its major compounds were ascaridole (23.18%), eucalyptol 
(17.20%), camphor (14.20%), p-cymene (7.91%), α-terpineol (4.69%), and isobornyl 
acetate (4.57%). CPLEO showed a hemolytic effect only at high concentrations 
(185.5-1000 mg/mL). It showed acute oral toxicity in mice with a LD50 of 
460.42 mg/kg. CPLEO (50-250 mg/kg) caused some significant changes in 
hematological and biochemical parameters. Histopathological evaluation indicated 
alterations in liver and kidneys but transaminases, urea and creatinine levels 
remained like the negative control. CPLEO administration impaired weight gain 
and reduced water and food consumption. Finally, it was not genotoxic by both 
comet and micronucleus tests. The results highlight the need for attention when 
choosing doses to evaluate the bioactivities of CPLEO.

Copyright © 2024 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.toxicon.2024.108147
PMID: 39433261

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. Food Chem Toxicol. 2024 Oct;192 Suppl 1:114822. doi:
10.1016/j.fct.2024.114822.  Epub 2024 Jun 16.

RIFM fragrance ingredient safety assessment, isobornyl acetate, CAS Registry 
Number 125-12-2.

Api AM(1), Bartlett A(1), Belsito D(2), Botelho D(1), Bruze M(3), 
Bryant-Freidrich A(4), Burton GA Jr(5), Cancellieri MA(1), Chon H(1), Dagli 
ML(6), Dekant W(7), Deodhar C(1), Farrell K(1), Fryer AD(8), Jones L(1), Joshi 
K(1), Lapczynski A(1), Lavelle M(1), Lee I(1), Moustakas H(1), Muldoon J(1), 
Penning TM(9), Ritacco G(1), Sadekar N(1), Schember I(1), Schultz TW(10), 
Siddiqi F(1), Sipes IG(11), Sullivan G(12), Thakkar Y(1), Tokura Y(13).

Author information:
(1)Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, 
Woodcliff Lake, NJ, 07677, USA.
(2)Expert Panel for Fragrance Safety, Columbia University Medical Center, 
Department of Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA.
(3)Expert Panel for Fragrance Safety, Malmo University Hospital, Department of 
Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, 
Malmo, SE-20502, Sweden.
(4)Expert Panel for Fragrance Safety, Pharmaceutical Sciences, Wayne State 
University, 42 W. Warren Ave., Detroit, MI, 48202, USA.
(5)Expert Panel for Fragrance Safety, School of Natural Resources & Environment, 
University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 
58109, USA.
(6)Expert Panel for Fragrance Safety, University of Sao Paulo, School of 
Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. dr. 
Orlando Marques de Paiva, 87, Sao Paulo, CEP 05508-900, Brazil.
(7)Expert Panel for Fragrance Safety, University of Wuerzburg, Department of 
Toxicology, Versbacher Str. 9, 97078, Würzburg, Germany.
(8)Expert Panel for Fragrance Safety, Oregon Health & Science University, 3181 
SW Sam Jackson Park Rd., Portland, OR, 97239, USA.
(9)Expert Panel for Fragrance Safety, University of Pennsylvania, Perelman 
School of Medicine, Center of Excellence in Environmental Toxicology, 1316 
Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, 
PA, 19104-3083, USA.
(10)Expert Panel for Fragrance Safety, The University of Tennessee, College of 
Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., 
Knoxville, TN, 37996- 4500, USA.
(11)Expert Panel for Fragrance Safety, Department of Pharmacology, University of 
Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, 
Tucson, AZ, 85724-5050, USA.
(12)Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, 
Woodcliff Lake, NJ, 07677, USA. Electronic address: gsullivan@rifm.org.
(13)Expert Panel for Fragrance Safety, The Journal of Dermatological Science 
(JDS), Department of Dermatology, Hamamatsu University School of Medicine, 
1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.

DOI: 10.1016/j.fct.2024.114822
PMID: 38889847 [Indexed for MEDLINE]

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. We wish to confirm that there are no known conflicts of interest 
associated with this publication and there has been no significant financial 
support for this work that could have influenced its outcome. RIFM staff are 
employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The 
Expert Panel receives a small honorarium for time spent reviewing the subject 
work.


3. Molecules. 2023 Feb 16;28(4):1875. doi: 10.3390/molecules28041875.

Study on Synthesizing Isobornyl Acetate/Isoborneol from Camphene Using 
α-Hydroxyl Carboxylic Acid Composite Catalyst.

Meng ZL(1)(2)(3), Qin RX(1), Wen RS(1), Li GQ(1), Liang ZY(1), Xie JK(1), Zhou 
YH(2), Yang ZQ(1).

Author information:
(1)Guangxi Key Laboratory of Superior Timber Trees Resource Cultivation, Guangxi 
Forestry Research Institute, Nanning 530002, China.
(2)Institute of Chemical Industry of Forest Products, Nanjing 210042, China.
(3)College of Chemical Engineering, Forestry University, Nanjing 210037, China.

This study examined the preparation of isobornyl acetate/isoborneol from 
camphene using an α-hydroxyl carboxylic acid (HCA) composite catalyst. Through 
the study of the influencing factors, it was found that HCA and boric acid 
exhibited significant synergistic catalysis. Under optimal conditions, when 
tartaric acid-boric acid was used as the catalyst, the conversion of camphene 
and the gas chromatography (GC) content and selectivity of isobornyl acetate 
were 92.9%, 88.5%, and 95.3%, respectively. With the increase in the ratio of 
water to acetic acid, the GC content and selectivity of isobornol in the product 
increased, but the conversion of camphene decreased. The yield of isobornol was 
increased by adding ethyl acetate or titanium sulfate/zirconium sulfate to form 
a ternary composite catalyst. When a ternary complex of titanium sulfate, 
tartaric acid, and boric acid was used as the catalyst, the GC content of 
isobornol in the product reached 55.6%. Under solvent-free conditions, mandelic 
acid-boric acid could catalyze the hydration reaction of camphene, the GC 
content of isoborneol in the product reached 26.1%, and the selectivity of 
isoborneol was 55.9%. The HCA-boric acid composite catalyst can use aqueous 
acetic acid as a raw material, which is also beneficial for the reuse of the 
catalyst.

DOI: 10.3390/molecules28041875
PMCID: PMC9964953
PMID: 36838861

Conflict of interest statement: There are no conflicts to declare.


4. Plants (Basel). 2022 Nov 26;11(23):3252. doi: 10.3390/plants11233252.

Anti-Inflammatory Activities of Constituents from Cinnamomum insularimontanum 
Hayata Leaves and Their Mechanisms.

Chen CY(1), Wu PC(2), Tsao NW(3), Tseng YH(1)(4), Chu FH(5), Wang SY(2)(3)(6).

Author information:
(1)Experimental Forest, College of Bio-Resources and Agriculture, National 
Taiwan University, Nantou County 55750, Taiwan.
(2)Department of Forestry, National Chung Hsing University, Taichung 40227, 
Taiwan.
(3)Special Crop and Metabolome Discipline Cluster, Academy Circle Economy, 
National Chung Hsing University, Taichung 40227, Taiwan.
(4)Taiwan Forestry Research Institute, Taipei 10551, Taiwan.
(5)School of Forestry and Resource Conservation, National Taiwan University, 
Taipei 10617, Taiwan.
(6)Agricultural Biotechnology Research Institute, Academia Sinica, Taipei 11529, 
Taiwan.

Cinnamomum insularimontanum is an endemic species of Taiwan. Although most 
Cinnamomum plants have significant biological activity, the bioactivity 
investment of C. insularimontanum is rare. Since inflammation plays an important 
role in many diseases, anti-inflammatory compounds can be developed into 
healthcare products. Therefore, we first conducted a study on the 
anti-inflammatory activity of C. insularimontanum leaves. First, we examined the 
antiinflammation activity of essential oil from C. insularimontanum leaves, and 
it revealed potent anti-inflammatory activity. A total of 23 volatile compounds 
were identified in C. insularimontanum leaves' essential oil by using GC/MS 
analysis. Among them were 1,8-cineole (35.94%), α-eudesmol (6.17%), pinene 
(7.55%), sabinene (5.06%), and isobornyl acetate (4.81%). According to previous 
studies, 1,8-cineole might be an anti-inflammation principal compound of C. 
insularimontanum leaves. Next, the ethanolic extracts of C. insularimontanum 
leaves also exhibited good anti-inflammatory activity. Two bioactive compounds, 
isoburmanol (F1) and burmanol (F2), were isolated from the ethyl acetate soluble 
fraction by using the bioactivity-guided separation protocol and spectroscopic 
analysis. F1 was obtained from C. insularimontanum for the first time, and F2 
was isolated for the first time from natural resources. Both F1 and F2 could 
inhibit the production of nitric oxide (NO), and the IC50 values were 14.0 μM 
and 43.8 μM, RAW 264.7 cells after induction of lipopolysaccharide. Furthermore, 
F1 and F2 also revealed significant inhabitation effects on iNOS and COX-2 
protein expression. The anti-inflammation activity of F1 and F2 was different 
from the common pathway of inhibiting NF-κB. Both of them could inhibit the 
production of NO and PGE2 by directly inhibiting the AP-1 (c-Jun) protein and 
then inhibiting the downstream iNOS and COX-2. Although both F1 and F2 possessed 
significant anti-inflammatory activity, the activity of F1 was better than F2. 
Through molecular docking simulation analysis, the results show that F1 and F2 
interact with AP-1, inhibit the binding of AP-1 to DNA, and cause AP-1 to fail 
to transcribe the related factors of inflammation. The binding ability of AP-1 
and F1 was stronger than F2, and that is the reason why F1 exhibited better 
activities in both downstream proteins and inflammatory cytokines. Based on the 
results obtained in this study, the essential oil and F1 and F2 isolated from C. 
insularimontanum leaves have good anti-inflammatory activities, and it is 
expected to be used as a reference for the development of medical care products 
in the future.

DOI: 10.3390/plants11233252
PMCID: PMC9736326
PMID: 36501293

Conflict of interest statement: The authors declare that there is no conflict of 
interest.


5. Plants (Basel). 2022 Apr 13;11(8):1054. doi: 10.3390/plants11081054.

Essential Oil Biodiversity of Achillea ligustica All. Obtained from Mainland and 
Island Populations.

Bader A(1), AlQathama A(1), Cioni PL(2), Ceccarini L(3), Abdelhady MIS(4), 
Al-Shareef W(5), Ascrizzi R(2), Flamini G(2).

Author information:
(1)Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, 
Makkah 21955, Saudi Arabia.
(2)Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, 
Italy.
(3)Department of Agriculture, Food and Environment, University of Pisa, Via del 
Borghetto 80, 56124 Pisa, Italy.
(4)Pharmacognosy Department, Faculty of Pharmacy, Helwan University, Cairo 
11795, Egypt.
(5)12 Tekne' Ricerche, Cittadella della Ricerca, S.S.7 Mesagne, 72100 Brindisi, 
Italy.

BACKGROUND: The genus Achillea is rich in essential oil (EO) with high chemical 
diversity. In this study, eight EO samples obtained from flowers and leaves of 
Achillea ligustica All. collected on the Mediterranean mainland and island 
locations were analyzed to evaluate their possible chemical diversity.
METHODS: Sixteen samples of EO were analyzed by GC-MS, leading to the 
identification of 95 compounds in the leaves and 86 compounds in the flowers; a 
statistical analysis was performed to determine the chemical polymorphism.
RESULTS: Monoterpenes, such as β-pinene, borneol, ɑ-terpineol and isobornyl 
acetate, were more abundant in the continental samples, while the insular 
samples were richer in 1,8-cineole. Fragranyl acetate and fragranol were 
detected in remarkable concentrations in sample 8. The fruits of sample 8 were 
then cultivated under controlled agronomic conditions, providing plants rich in 
these compounds (sample 9). The geographical variability influenced the EO 
compositions, with unique observed chemotypes and a high degree of diversity 
among samples collected in various areas (mainland or island). Statistical 
analyses did not reveal any pattern between the geographical provenience and the 
compositions.
CONCLUSION: Samples were distributed based on the plant organ, confirming the 
already reported high degree of chemical polymorphism of this species. Sample 8 
could be used as a source of fragranol and fragranyl acetate, with potential 
applications in the insecticidal and pheromone industries.

DOI: 10.3390/plants11081054
PMCID: PMC9027389
PMID: 35448782

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