Preliminary Evaluation of Acute Toxicity and Hypoglycemic Effects of Salvia officinalis L. Extract in Healthy Male Rabbits: An Animal Model Study

Authors

  • Hisham A. Al-khawlani Department of Pharmacy, Albaydha University Institute for Continuing Education, Albaydha University, Albaydha, Yemen. Author
  • Shatha Al-Fthahy Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Safa'a Amer Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Resalh Jubra Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Maram Al-Mashrama Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Malak Al-Magmhi Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Hanan Al-Nahary Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Hadeel Al-Mekhlafi Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Amal Al-Nahary Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Aisha Al-Habri Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author
  • Nabil Ali Al-Mekhlafi Department of Biochemical Technology, Faculty of Applied Science, Thamar University, Dhamar 87246, Yemen. Author
  • Wala'a Amran Department of Pharmacy, Thamar University Institute for Continuing Education, Thamar University, Dhamar 87246, Yemen. Author

DOI:

https://doi.org/10.59167/tj3pbg80

Keywords:

Salvia officinalis, Hypoglycemic, Acute Toxicity, Rabbit Model, Safety Assessment

Abstract

Background: Salvia officinalis L. is an aromatic perennial herb belonging to the Lamiaceae family, known for its diverse pharmacological properties, including potent antioxidant, antimicrobial, anti-inflammatory, neuroprotective, and anti-diabetic activities. Despite its extensive traditional use, the specific roles of S. officinalis in glucose management and its acute toxicity profile in rabbits require further elucidation. Objective: This study provided a preliminary assessment of the acute toxicity profile and the basal glycemic effects of a methanolic extract of S. officinalis in a normoglycemic rabbit model. Methodology: Twelve adult male White rabbits were randomly assigned to four groups (n=3). Group I served as the vehicle control, while Groups II, III, and IV received single oral doses of S. officinalis extract at 1000, 1500, and 2000 mg/kg, respectively. Animals were monitored over 14 days for toxicity, mortality, and body weight, alongside repeated measurements of fasting blood glucose (FBG). Data were analyzed using two-way repeated measures ANOVA. Results: S. officinalis extract demonstrated dose-dependent basal glucose modulation. The repeated measures analysis revealed highly significant effects for both time and dose (P < 0.001). The 1000 mg/kg dose was identified as the No Observed Adverse Effect Level (NOAEL), while the 1500 mg/kg dose was established as the Maximum Tolerated Dose (MTD). At 2000 mg/kg, an observed lethal threshold was recorded with a 66.7% mortality rate. Conclusion: The preliminary findings suggest that S. officinalis extract exhibits potential dose-dependent hypoglycemic activity in normoglycemic models. However, the manifestation of systemic toxicity at higher concentrations defines a narrow therapeutic window for the extract.

References

[1] Belhadj, S., Hentati, O., Hammami, M., Ben Hadj, A., Boudawara, T., Dammak, M., Zouari, S., El Feki, A. (2018) Metabolic impairments and tissue disorders in alloxan-induced diabetic rats are alleviated by Salvia officinalis L. essential oil, Biomedicine & Pharmacotherapy 108: 985-995.

[2] Alarcon‐Aguilar, F.J., Roman‐Ramos, R., Flores‐Saenz, J.L., Aguirre‐Garcia, F. (2002) Investigation on the hypoglycaemic effects of extracts of four Mexican medicinal plants in normal and Alloxan‐diabetic mice, Phytotherapy Research 16: 383-386.

[3] Hossain, M.J., Al‐Mamun, M., Islam, M.R. (2024) Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused, Health Science Reports 2024: e2004.

[4] Eidi, M., Eidi, A., Zamanizadeh, H. (2005) Effect of Salvia officinalis L. leaves on serum glucose and insulin in healthy and streptozotocin-induced diabetic rats, Journal of Ethnopharmacology 100: 310-313.

[5] Willcox, M.L., Elugbaju, C., Al-Anbaki, M., Lown, M., Graz, B. (2021) Effectiveness of Medicinal Plants for Glycaemic Control in Type 2 Diabetes: An Overview of Meta-Analyses of Clinical Trials, Frontiers in Pharmacology 12.

[6] Anjali, Deepak, G., Pragi, Varun, K., Dimple, Monika (2024) A Review of Therapeutic Properties and Uses of Salvia officinalis, Journal of Pharma Insights and Research 2: 146-154.

[7] Ghorbani, A., Esmaeilizadeh, M. (2017) Pharmacological properties of Salvia officinalis and its components, Journal of Traditional and Complementary Medicine 7: 433-440.

[8] Ashkani-Esfahani, S., Noorafshan, A., Ebrahimi, A., Bahmani-Jahromi, M., Imanieh, M.-H., Ebrahimi, S., Hosseini, S., Tanideh, N. (2022) Salvia Officinalis Protects Pancreatic Beta-cells Against Streptozotocin-Induced Damage; A Stereological Study, Jundishapur Journal of Natural Pharmaceutical Products 17: e109906.

[9] Ezema, C.A., Ezeorba, T.P.C., Aguchem, R.N., Okagu, I.U. (2022) Therapeutic benefits of Salvia species: A focus on cancer and viral infection, Heliyon 8: e08763.

[10] Hasanein, P., Felehgari, Z., Emamjomeh, A. (2016) Preventive effects of Salvia officinalis L. against learning and memory deficit induced by diabetes in rats: Possible hypoglycaemic and antioxidant mechanisms, Neuroscience Letters 622: 72-77.

[11] Rhaimi, S., Brikat, S., Lamtai, M., Ouhssine, M. (2023) Acute Oral Toxicity and Neurobehavioral Effects of Salvia officinalis Essential Oil in Female Wistar Rats, Advances in Animal and Veterinary Sciences 11: 654–662.

[12] Sá, C.M., Ramos, A.A., Azevedo, M.F., Lima, C.F., Fernandes-Ferreira, M., Pereira-Wilson, C. (2009) Sage Tea Drinking Improves Lipid Profile and Antioxidant Defences in Humans, International Journal of Molecular Sciences 10: 3937-3950.

[13] Christensen, K.B., Jørgensen, M., Kotowska, D., Petersen, R.K., Kristiansen, K., Christensen, L.P. (2010) Activation of the nuclear receptor PPARγ by metabolites isolated from sage (Salvia officinalis L.), Journal of Ethnopharmacology 132: 127-133.

[14] Falya, Y., Sumiwi, S.A., Levita, J. (2013) Mini Review: Toxicity Study of Plant Extracts, IOSR Journal of Pharmacy and Biological Sciences 6: 25-32.

[15] Amini, L., Mojab, F., Jahanfar, S., Sepidarkish, M., Raoofi, Z., Maleki-Hajiagha, A. (2020) Efficacy of Salvia officinalis extract on the prevention of insulin resistance in euglycemic patients with polycystic ovary syndrome: A double-blinded placebo-controlled clinical trial, Complementary Therapies in Medicine 48: 102245.

[16] Ollanketo, M., Peltoketo, A., Hartonen, K., Hiltunen, R., Riekkola, M.-L. (2002) Extraction of sage (Salvia officinalis L.) by pressurized hot water and conventional methods: antioxidant activity of the extracts, European Food Research and Technology 215: 158-163.

[17] Mokogwu, A.T.H., Adjekuko, C.O., Oshilonyah, U.H., Ikpefan, J.O., Eyenubo, O.B., Avwioro, O.G. (2022) Hypoglycaemic and Hypolipidemic Effects of Alcoholic Extract of Common Sage (Salvia Officinalis) In Streptozotocin –Induced Diabetic Rabbits, African Journal of Biomedical Research 25: 243-247.

[18] Iravani, M., Mahinpour, R., Zahraei, Z., Toluei, Z., Asgari, F., Haghighipour, N. (2020) Comparison of cytotoxic and antioxidant activities and phenol content of four Salvia L. species from Iran, Journal of Medicinal Plants 19: 59-68.

[19] Nutrizio, M., Gajdoš Kljusurić, J., Badanjak Sabolović, M., Bursać Kovačević, D., Šupljika, F., Putnik, P., Semenčić Čakić, M., Dubrović, I., Vrsaljko, D., Maltar-Strmečki, N., Režek Jambrak, A. (2020) Valorization of sage extracts (Salvia officinalis L.) obtained by high voltage electrical discharges: Process control and antioxidant properties, Innovative Food Science & Emerging Technologies 60: 102284.

[20] Organisation for Economic Co-operation and Development OECD. (2025) Guideline No. 497: Defined Approaches on Skin Sensitisation. OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, France, pp 20.

[21] Chow, P.K.H., Ng, R.T.H., Ogden, B.E. (2008) Using Animal Models in Biomedical Research, World Scientific Publication, Singapore, pp. 308.

[22] Obernier, J.A., Baldwin, R.L. (2006) Establishing an Appropriate Period of Acclimatization Following Transportation of Laboratory Animals, Institute for Laboratory Animal Research (ILAR) Journal 47: 364-369.

[23] Javid, H., Moein, S., Moein, M. (2022) An investigationof the inhibitory effects of dichloromethane and methanol extracts of Salvia macilenta, Salvia officinalis, Salvia santolinifola and Salvia mirzayanii on diabetes marker enzymes, an approach for the treatment diabetes, Clinical Phytoscience 8: 7.

[24] Al-Mekhlafi, N.A., Al-Badaii, F., Al-Ezzi, M.S., Al-Yamani, A., Almakse, E., Alfaqeeh, R., Al-Hatar, G., Al-Twity, M., Al-Masadi, M., Abdullah, M., Al-Qarhami, N. (2023) Phytochemical Analysis and Antibacterial Studies of Some Yemeni Medicinal Plants against Selected Common Human Pathogenic Bacteria, Thamar University Journal of Natural & Applied Sciences 8: 14–18.

[25] Samer, B.S., Al-Mausmi, H., Gailan, A., Ziad, S., Saleh, M., Shalan, A., Hamdan, M., Gharab, A., Al-Ra'ai, A., Al-Ra’ai, N.A.-D., Al-Ezzi, M. (2024) Phytochemical Screening and Antibacterial Activity of Leaf Extracts from Psiadia Punctulata, Thamar University Journal of Natural & Applied Sciences 9: 31–41.

[26] Abubakar, A.R., Haque, M. (2020) Preparation of Medicinal Plants: Basic Extraction and Fractionation Procedures for Experimental Purposes, Journal of Pharmacy and Bioallied Sciences 12: 1-10.

[27] Lamia, A.K.R., Al-Mashhady, A. (2016) Hypoglycemic effect of Salvia officinalis L. extracts on induced diabetic rabbits, International Journal of PharmTech Research 9: 252-260.

[28] Kanana, F.M., Maina, C.M., Kibet, J.M., Clement, J.M. (2020) Hypoglycaemic effects of Salvia officinalis extracts on alloxan-induced diabetic Swiss albino mice, Journal of Medicinal Plants Research 14: 518-525.

[29] Skalli, S., Hassikou, R., Arahou, M. (2019) An ethnobotanical survey of medicinal plants used for diabetes treatment in Rabat, Morocco, Heliyon 5: e01421.

[30] Bouteldja, R., Doucene, R., Aggad, H., Abdi, F.Z., Belkhodja, H., Belal, A., Abdali, M., Zidane, K. (2023) Phytochemical screening, acute toxicity and antidiabetic activity of ethanolic extract of Salvia officinalis L. in Wistar Rat, Agriculturae Conspectus Scientificus 88: 351-357.

[31] Hinad, I., S'Hih, Y., Elhessni, A., Mesfioui, A., Ouahidi, M.l. (2022) Medicinal plants used in the traditional treatment of diabetes in Ksar Elkebir Region (North-Western Morocco), Pan African Medical Journal 42: 319.

[32] Gebru, A., Sibhat, G., Hiben, M. (2014) Preliminary phytochemical screening and blood glucose lowering activity of methanol extract of Salvia tilifolia Vahl aerial part, International Journal of Pharmaceutical and Biological Archive 5: 122-125.

[33] Ben Khedher, M.R., Hammami, M., Arch, J.R.S., Hislop, D.C., Eze, D., Wargent, E.T., Kępczyńska, M.A., Zaibi, M.S. (2018) Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone, PeerJ 6: e4166.

[34] Pereira, O.R., Catarino, M.D., Afonso, A.F., Silva, A.M.S., Cardoso, S.M. (2018) Salvia elegans, Salvia greggii and Salvia officinalis Decoctions: Antioxidant Activities and Inhibition of Carbohydrate and Lipid Metabolic Enzymes, Molecules 23: 3169.

[35] Oliveira, G.O., Braga, C.P., Fernandes, A.A.H. (2013) Improvement of biochemical parameters in type 1 diabetic rats after the roots aqueous extract of yacon [Smallanthus sonchifolius (Poepp.& Endl.)] treatment, Food and Chemical Toxicology 59: 256-260.

[36] Ebru K, F., A, A., K, C. (2017) Extraction and HPLC Analysis of Sage (Salvia officinalis) Plant, Natural Products Chemistry & Research 05: 298.

[37] Dinel, A.-L., Lucas, C., Guillemet, D., Layé, S., Pallet, V., Joffre, C. (2020) Chronic Supplementation with a Mix of Salvia officinalis and Salvia lavandulaefolia Improves Morris Water Maze Learning in Normal Adult C57Bl/6J Mice, Nutrients 12: 1777.

Downloads

Published

29-06-2026

How to Cite

Preliminary Evaluation of Acute Toxicity and Hypoglycemic Effects of Salvia officinalis L. Extract in Healthy Male Rabbits: An Animal Model Study (H. A. . Al-khawlani, S. Al-Fthahy, S. . . Amer, R. . Jubra, M. . Al-Mashrama, M. . Al-Magmhi, H. . Al-Nahary, H. Al-Mekhlafi, A. . Al-Nahary, A. . Al-Habri, N. A. . Al-Mekhlafi, & W. . Amran, Trans.). (2026). Thamar University Journal of Natural & Applied Sciences, 11(1), 34-39. https://doi.org/10.59167/tj3pbg80

Similar Articles

1-10 of 24

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)