Phenolic Profiling and OECD-Guided Acute and Subacute Oral Toxicity Assessment of Cannabis sativa L. Seed Hydroethanolic Extract
8 affiliations
- 1Human Nutrition, Bioactives and Oncogenetics Team, Faculty of Sciences, Moulay Ismail University, Meknes 50070, Morocco
- 2Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research Centre, Mohammed V University, Rabat 1014, Morocco
- 3Laboratory of Pharmacology, National Agency for Medicinal and Aromatic Plants, Taounate 34025, Morocco
- 4Applied Chemistry Research Unit, Faculty of Science and Techniques, Abdelmalek Essaadi University, Al-Hoceima 32000, Morocco
- 5Laboratory of Drug Sciences, Faculty of Medicine, Pharmacy, and Dental Medicine of Fez, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco
- 6Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal 23000, Morocco
- 7Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
- 8Department of Biostatistics and Mathematics, Faculty of Pharmacy, Paris Cité University, 4, Avenue de l’Observatoire, 75006 Paris, France
Abstract
Cannabis sativa L. seeds have been traditionally used in Moroccan folk medicine and are increasingly recognized as a valuable source of nutrients and bioactive phytochemicals with promising therapeutic properties. Despite their widespread traditional and nutritional use, scientific evidence supporting their toxicological safety remains limited. This study aimed to characterize the phenolic profile of a hydroethanolic extract of Cannabis sativa L. seeds and to evaluate its acute and 28-day repeated-dose oral toxicity in mice following the Organization for Economic Cooperation and Development (OECD) guidelines. The phenolic composition of the extract was analyzed using high-performance liquid chromatography coupled with diode-array detection (HPLC-DAD). Acute oral toxicity was assessed according to OECD Guideline 423 after a single oral administration of 5000 mg/kg body weight. Repeated-dose oral toxicity was evaluated following OECD Guideline 407 by administering the extract orally at doses of 500 and 1000 mg/kg/day for 28 consecutive days. Clinical observations, body weight, food and water intake, relative organ weights, hematological and biochemical parameters, and histopathological examinations of the liver and kidneys were performed. HPLC-DAD analysis identified seven major phenolic compounds, namely catechin, chlorogenic acid, caffeic acid, vanillin, p-coumaric acid, quercetin, and kaempferol. No mortality, behavioral abnormalities, or treatment-related clinical signs were observed during either the acute or repeated-dose studies. The extract produced no significant alterations in body weight gain, food and water consumption, relative organ weights, liver and kidney histology, or most hematological and biochemical parameters. A significant reduction in serum total cholesterol and triglyceride levels was observed in treated animals, while platelet counts were significantly reduced only in female mice receiving 1000 mg/kg/day. Under the experimental conditions employed, the hydroethanolic extract of Cannabis sativa L. seeds exhibited a favorable oral safety profile, with an estimated LD50 greater than 5000 mg/kg. These findings support the traditional use and potential nutraceutical applications of Cannabis sativa seeds and provide a scientific basis for further pharmacological investigations and long-term safety studies.
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BibTeX
@article{elmernissi2026phenolic,
title = {{Phenolic Profiling and OECD-Guided Acute and Subacute Oral Toxicity Assessment of Cannabis sativa L. Seed Hydroethanolic Extract}},
author = {Rafik El-Mernissi and Naoual El Menyiy and Aziz Zouhri and Yahya El-Mernissi and Ghizlane Nouioura and Mohamed Bouhrim and Moneerah J. Alqahtani and Jawaher H. Alqahtani and Joe Miantezila Basilua and Nadia Senhaji and Oualid Abboussi and Lhoussain Hajji},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203587},
url = {https://www.mdpi.com/1420-3049/31/20/3587},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Phenolic Profiling and OECD-Guided Acute and Subacute Oral Toxicity Assessment of Cannabis sativa L. Seed Hydroethanolic Extract
AU - Rafik El-Mernissi
AU - Naoual El Menyiy
AU - Aziz Zouhri
AU - Yahya El-Mernissi
AU - Ghizlane Nouioura
AU - Mohamed Bouhrim
AU - Moneerah J. Alqahtani
AU - Jawaher H. Alqahtani
AU - Joe Miantezila Basilua
AU - Nadia Senhaji
AU - Oualid Abboussi
AU - Lhoussain Hajji
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203587
UR - https://www.mdpi.com/1420-3049/31/20/3587
AB - Cannabis sativa L. seeds have been traditionally used in Moroccan folk medicine and are increasingly recognized as a valuable source of nutrients and bioactive phytochemicals with promising therapeutic properties. Despite their widespread traditional and nutritional use, scientific evidence supporting their toxicological safety remains limited. This study aimed to characterize the phenolic profile of a hydroethanolic extract of Cannabis sativa L. seeds and to evaluate its acute and 28-day repeated-dose oral toxicity in mice following the Organization for Economic Cooperation and Development (OECD) guidelines. The phenolic composition of the extract was analyzed using high-performance liquid chromatography coupled with diode-array detection (HPLC-DAD). Acute oral toxicity was assessed according to OECD Guideline 423 after a single oral administration of 5000 mg/kg body weight. Repeated-dose oral toxicity was evaluated following OECD Guideline 407 by administering the extract orally at doses of 500 and 1000 mg/kg/day for 28 consecutive days. Clinical observations, body weight, food and water intake, relative organ weights, hematological and biochemical parameters, and histopathological examinations of the liver and kidneys were performed. HPLC-DAD analysis identified seven major phenolic compounds, namely catechin, chlorogenic acid, caffeic acid, vanillin, p-coumaric acid, quercetin, and kaempferol. No mortality, behavioral abnormalities, or treatment-related clinical signs were observed during either the acute or repeated-dose studies. The extract produced no significant alterations in body weight gain, food and water consumption, relative organ weights, liver and kidney histology, or most hematological and biochemical parameters. A significant reduction in serum total cholesterol and triglyceride levels was observed in treated animals, while platelet counts were significantly reduced only in female mice receiving 1000 mg/kg/day. Under the experimental conditions employed, the hydroethanolic extract of Cannabis sativa L. seeds exhibited a favorable oral safety profile, with an estimated LD50 greater than 5000 mg/kg. These findings support the traditional use and potential nutraceutical applications of Cannabis sativa seeds and provide a scientific basis for further pharmacological investigations and long-term safety studies.
SN - 1420-3049
ER -