Assessment of Acute Toxicity and Analgesic Effect of Cedrus atlantica (Endl.) G. Manetti ex Carrière Stem Extracts

Main Article Content

Mouna Ameggouz
Soufiane Drioua
Otman El-Guourrami
Hanane Azalmad
Khairo El Baria Metni
Loubna Koursaoui
Ahmed Zahidi
Anass Doukkali
Badr Satrani
Hanane Benzeid

Abstract

Cedrus atlantica is a Mediterranean medicinal plant used traditionally for the treatment of
urinary tract infections and cancer. This study aims to evaluate the toxicity and analgesic
properties of the stem extracts of Cedrus atlantica.Powdered stem of Cedrus atlantica was
extracted successively with cyclohexane, ethyl acetate, and ethanol, in a Soxhlet apparatus, to
yield extracts F1, F2, and F3, respectively. An aqueous extract (F4) was obtained by maceration
of the residue at room temperature. Acute oral toxicity of the extracts was assessed in mice
according to OECD guidelines. Analgesic activity of the extracts (500 mg/kg) was evaluated
using the writhing and tail immersion tests, with aspirin (125 mg/kg), and morphine (0.1 mg/kg)
as positive controls, respectively.Acute toxicity studies showed that Cedrus atlantica stem
extracts have no significant toxic effects at a dose of 2000 mg/kg. In the writhing test, the
aqueous extract (F4) demonstrated the highest analgesic activity with 18.33±1.55 writhes
(50.66% inhibition), followed by the ethyl acetate extract (F2) with 19.33±1.77 writhes (47.97%
inhibition). F2 and F4 were more effective than aspirin which caused 21.66±1.88 writhes
(41.70% inhibition). In the tail immersion test, F2 and F4 showed significant central analgesic
activity, both extracts significantly increased the reaction times, with F2 peaking at 5.02±0.45
seconds and F4 at 4.92±0.30 seconds, compared to morphine with reaction time of 7.70±0.18
seconds. These findings therefore suggest that Cedrus atlantica stem extracts are relatively safe
on acute oral administration, and have potential for use as analgesic agent.

Downloads

Download data is not yet available.

Article Details

How to Cite
Ameggouz, M., Drioua, S., El-Guourrami, O., Azalmad, H., Metni, K. E. B., Koursaoui, L., Zahidi, A., Doukkali, A., Satrani, B., & Benzeid, H. (2024). Assessment of Acute Toxicity and Analgesic Effect of Cedrus atlantica (Endl.) G. Manetti ex Carrière Stem Extracts. Tropical Journal of Natural Product Research (TJNPR), 8(7), 7677-7681. https://doi.org/10.26538/tjnpr/v8i7.7
Section
Articles
Author Biography

Mouna Ameggouz, Laboratory of Analytical Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco

Chemistry and Microbiology Laboratories, Forest Research Center, Avenue Omar Ibn El Khattab, BP 763, Agdal, Morocco.

How to Cite

Ameggouz, M., Drioua, S., El-Guourrami, O., Azalmad, H., Metni, K. E. B., Koursaoui, L., Zahidi, A., Doukkali, A., Satrani, B., & Benzeid, H. (2024). Assessment of Acute Toxicity and Analgesic Effect of Cedrus atlantica (Endl.) G. Manetti ex Carrière Stem Extracts. Tropical Journal of Natural Product Research (TJNPR), 8(7), 7677-7681. https://doi.org/10.26538/tjnpr/v8i7.7

References

Ait Sidi Brahim M, Markouk M, Larhsini M. Moroccan

Medicinal Plants as Antiinfective and Antioxidant Agents.

In New Look to Phytomedicine: Advancements in Herbal

Products as Novel Drug Leads. 2019; p. 91‑142.

https://doi.org/10.1016/B978-0-12-814619-4.00005-7.

Drioua S, Cherkani-Hassani A, El-guourrami O, Ameggouz

M, Zahidi A, Bouyahaya A, Ibrahim Shah S, Mohammed

Al-Worafi Y, Chiau Ming L, Benzaied H, Doukkali A.

Toxicological Review of Anticancer Plants Used in

Traditional Medicine in Morocco. Prog Microbes Mol Biol.

; 6(1):1‑45. https://doi.org/10.36877/pmmb.a0000328.

Zaher A, Boufellous M, Jaber H, El Hartiti H, Barrahi M,

Ouhssine M, Bourkhiss B. Ethnobotanical Study of

Medicinal Plants Used in the Province of Sidi Slimane

(Morocco). J Bioresource Med. 2018; 06(09):25‑35.

https://doi.org/10.4236/jbm.2018.69003.

Salhi N, El-guourrami O, Rouas L, Moussaid S, Moutawalli

A, Benkhouili F, Ameggouz M, Alshahrani M, Awadh A,

Bouyahya A, My El Abbes F, Cherrah Y. Evaluation of the

Wound Healing Potential of Cynara humilis Extracts in the

Treatment of Skin Burns. Evid Based Complement Alternat

Med. 2023; 2023:1‑12.

https://doi.org/10.1155/2023/5855948.

Salhi N, El Guourrami O, Balahbib A, Rouas L, Moussaid

S, Moutawalli A, Benkhouili F, Ameggouz M, Ullah R,

Alotaibi A, Bouyahya A, Siang Tan C, Chiau Ming L, my

el abbes F, Cherrah Y. Application of Aleppo pine extract

for skin burn treatment. J Appl Biomater Funct Mater.

; 22:22808000241236020.

https://doi.org/10.1177/22808000241236020.

Najem M, Daoudi A, Bouiamrine EH, Ibijbijen J, Nassiri L.

Biodiversity of poisonous medicinal plants solicited in the

traditional phytotherapy of the central Middle Atlas -

Morocco-. Ethnobot Res Appl. 2019; 18:1‑22.

http://dx.doi.org/10.32859/era.18.19.1-22.

Drioua S, Azalmad H, El-Guourrami O, Ameggouz M,

Benkhouili FZ, Assouguem A, Kara M, Ullah R, Ali E A,

Ercisli S, Fidan H, Benzeid H, Doukkali A. Phytochemical

screening and antioxidant activity of Vitex agnus-castus L.

Open Chem. 2024; 22(1):20230190.

https://doi.org/10.1515/chem-2023-0190.

Drioua S, El-Guourrami O, Assouguem A, Ameggouz M,

Kara M, Ullah R , Bari A, Zahidi A, Skender A, Benzeid A,

Doukkali A. Phytochemical study, antioxidant activity, and

dermoprotective activity of Chenopodium ambrosioides

(L.). Open Chem. 2024; 22(1): 20230194.

https://doi.org/10.1515/chem-2023-0194.

Mahraz AM, Elhachmia C, Zakia R, Taleb M. Medicinal

Plants of Moulay Yaâcoub Province in Morocco: An

Ethnobotanical and Biodiversity Survey. Trop J Nat Prod

Res. 2023; 7(8): 3590–3601.

http://www.doi.org/10.26538/tjnpr/v7i8.3.

Serbouti S, Abbas Y, Soussi M, Alaoui I, Squalli W,

Achiban H. Morphological Responses of Cedrus atlantica,

Pinus halepensis, and Tetraclinis articulata in Different

Pedoclimatic Conditions. Trop J Nat Prod Res. 2022;

(12):1919–1924.

http://www.doi.org/10.26538/tjnpr/v6i12.3.

Hamilton AC. Medicinal plants, conservation and

livelihoods. Biodivers Conserv. 2004; 13(8):1477‑517.

Ameggouz M, Drioua S, El-Guourrami O, Azalmad H,

Ouajdi M, Zahidi A, Doukkali A, Satani B, Benzeid H.

Phytochemical Analysis and Evaluation of the Antioxidant

Activity of Cedrus atlantica (Endl.) G. Manetti ex Carrière

Stem Extracts. Trop J Nat Prod Res. 2024;8(3):6741‑6750.

https://doi.org/10.26538/tjnpr/v8i3.40

Bouayyadi L, El Hafian M, Zidane L. Étude floristique et

ethnobotanique de la flore médicinale dans la région du

Gharb, Maroc. J Appl Biosci. 2015; 93(1):8770.

https://doi.org/10.4314/jab.v93i1.10.

Schnaubelt K. Medical Aromatherapy: Healing with

Essential Oils. Berkeley, CA: Frog [Online]. 1999 [cited

Feb 1]. Available from:

https://www.biblio.com/book/medical-aromatherapyhealing-essential-oils-schnaubelt/d/1276415526.

Lawless J. The encyclopeadia of essential oils: a complete guide to the use of aromatics in aromatherapy, herbalism,

health & well-being. Shaftsbury, Dorset: Element; 1992.

Lawrence BM. Progress in Essential Oils. Perfumer &

Flavorist [Online]. 2012 [cited 2022 Feb 1]. Available from:

https://www.perfumerflavorist.com/fragrance/ingredients/ar

ticle/21859574/progress-in-essential-oils.

Davis P. Aromatherapy: An A-Z Patricia Davis - broché -

Patricia Davis - Achat Livre | fnac [Internet]. 1999 [cité 1

févr 2022]. Disponible sur:

https://livre.fnac.com/mp34287014/Aromatherapy-An-A-Z

Mojay G. Aromatherapy for healing the spirit : restoring

emotional and mental balance with essential oils /. Healing

Arts Press; 1999.

FischerRizzi S. The Complete Aromatherapy Handbook:

Essential Oils for Radiant Health par Susanne FischerRizzi: Used: Acceptable Paperback (1990) | Lady Lisa’s

Bookshop [Online]. 1990 [cited 2022 Feb 1]. Available

from: https://www.abebooks.fr/9780806982229/CompleteAromatherapy-Handbook-Essential-Oils-0806982225/plp.

Pazinato R, Volpato A, Baldissera MD, Santos RCV,

Baretta D, Vaucher RA, Giongo JL, Boligon AA, Stefani

LM, Da Silva AS. In vitro effect of seven essential oils on

the reproduction of the cattle tick Rhipicephalus microplus.

J Adv Res. 2016; 7(6):1029‑1034.

https://doi.org/10.1016/j.jare.2016.05.003.

Benouaklil F, Hamaidi-Chergui F, Hamaidi MS, Saidi F.

Chemical Composition and Antimicrobial Properties of

Algerian Cedrus atlanticam. Essential Oils | Agrobiologia

[Online]. 2017 [cited 2022 Feb 1]. Available from:

https://agrobiologia.net/online/chemical-composition-andantimicrobial-properties-of-algerian-cedrus-atlanticamessential-oils/.

Oukhrib A, Zaki M, Ait El Had M, Karroumi J, Bouamama

H, Benharref A, Urrutigoïty M. Synthesis of cyclopropane

ring derivatives from natural β- himachalene and evaluation

of their antimicrobial activity by bioautography. Rhazes

Gac. 2019; 6:61‑70.

Bennouna F, Lachkar M, EL Abed S, Saad I. Cedrus

atlantica essential oil: Antimicrobial activity and effect on

the physicochemical properties of cedar wood Surface.

Moroc J Biol. 2020; 16:35‑45.

Belkacem N, Khettal B, Hudaib M, Bustanji Y, AbuIrmaileh B, Amrine CSM. Antioxidant, antibacterial, and

cytotoxic activities of Cedrus atlantica organic extracts and

essential oil. Eur J Integr Med. 2021; 42:101292.

https://doi.org/10.1016/j.eujim.2021.101292.

Zrira S and Ghanmi M. Chemical Composition and

Antibacterial Activity of the Essential of Cedrus atlantica

(Cedarwood oil). J. Essent Oil-Bear Plants. 2016;

:1267‑1272.

https://doi.org/10.1080/0972060X.2015.1137499.

Emer AA, Donatello NN, Batisti AP, Oliveira Belmonte

LA, Santos ARS, Martins DF. The role of the

endocannabinoid system in the antihyperalgesic effect of

Cedrus atlantica essential oil inhalation in a mouse model

of postoperative pain. J Ethnopharmacol. 2018;

:477‑484. https://doi.org/10.1016/j.jep.2017.09.011.

Hung PH, Hsieh MC, Lee SC, Huang XF, Chang KF, Chen

SY, Lee MS, Tsai NM. Effects of Cedrus atlantica extract

on acute myeloid leukemia cell cycle distribution and

apoptosis. Mol Biol Rep. 2020; 47(11):8935‑8947.

https://doi.org/10.1007/s11033-020-05947-w.

Chang KF, Chang JT, Huang XF, Huang YC, Li CY, Weng

JC, Hsiao CY, Hsu HJ, Tsai NM. Cedrus atlantica Extract

Suppress Glioblastoma Growth through Promotion of

Genotoxicity and Apoptosis: In Vitro and In Vivo Studies.

Int J Med Sci. 2021; 18(11):2417‑2430.

https://doi.org/10.7150/ijms.54468.

Orchard A, Van vuuren S, Viljoen A. Commercial Essential

Oil Combinations against Topical Fungal Pathogens. Nat

Prod Commun. 2019; 14:1934578X1901400.

https://doi.org/10.1177/1934578X1901400139.

Ainane A, Benhima R, Khammour F, el Kouali M, Talbi M,

Abba EH, Cherroud S, Tarik A. Chemical composition and

insecticidal activity of five essential oils: Cedrus atlantica,

Citrus limonum, Rosmarinus officinalis, Syzygium

aromaticum and Eucalyptus globules. Mater Today: Proc.

; P 474-485.

https://doi.org/10.1016/j.matpr.2019.04.004.

Alves TJS, Murcia A, Wanumen AC, Wanderley-Teixeira

V, Teixeira ÁAC, Ortiz A, Medina P. Composition and

Toxicity of a Mixture of Essential Oils Against

Mediterranean Fruit Fly, Ceratitis capitata (Wiedemann)

(Diptera: Tephritidae). J Econ Entomol. 2019;

(1):164‑172. https://doi.org/10.1093/jee/toy275.

Fadel H, Benayache F, Samir B. Antioxidant properties of

four Algerian medicinal and aromatic plants Juniperus

oxycedrus L., Juniperus phoenicea L., Marrubium vulgare

L. and Cedrus atlantica (Manetti ex Endl). Sch Res J. 2016;

:72‑79.

Jaouadi I, Cherrad S, Bouyahya A, Koursaoui L, Satrani B,

Ghanmi M, Chaouch A. Chemical variability and

antioxidant activity of Cedrus atlantica Manetti essential

oils isolated from wood tar and sawdust. Arab J Chem.

; 14(12):103441.

https://doi.org/10.1016/j.arabjc.2021.10344.

Rostagno MA and Prado JM. Natural Product Extraction:

Principles and Applications. RSC; 2013. 1032 p.

Koster R, Anderson W, De Beer E. Acetic acid for

analgesic screening. In Federation Proceedings; 1959.

El-guourrami O, Drioua S, Ameggouz M, Salhi N, Sayah K,

Zengin G, Zahidi A, Doukkali A, Benzeid H. Antioxidant

activity, analgesic activity, and phytochemical analysis of

Ammi majus (L.) extracts. Int J Second Metabol. 2023;

:23‑37. https://doi.org/10.21448/ijsm.1139246.

Sewell RDE and Spencer PSJ. Antinociceptive activity of

narcotic agonist and partial agonist analgesics and other

agents in the tail-immersion test in mice and rats.

Neuropharmacol. 1976; 15(11):683‑688.

El-guourrami O, Salhi N, Benkhouili FZ, Zengin G, Yilmaz

MA, Ameggouz M, Zahidi A, Rouas L, Bouyahya A, Goh

KW, Sam TH, Ming LC, Doukkali A, Benzeid H.

Phytochemical composition and toxicity assessment of

Ammi majus L. Asian Pac J Trop Biomed. 2023; 13(4):165.

https://doi.org/10.4103/2221-1691.374233

Karrat L, Abajy MY, Nayal R. Investigating the antiinflammatory and analgesic properties of leaves ethanolic

extracts of Cedrus libani and Pinus brutia. Heliyon. 2022;

(4):e09254.