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  3. Vol. 21 No. 1 (2025): IJPS_Volume 21_Issue 1 (2025)
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Vol. 21 No. 1 (2025)

January 2025

Anxiolytic and Potential Neurotoxic Effects of Salvia hypoleuca in Mice

  • Marjan Talebi
  • Reyhaneh Alinejad
  • Nima Naderi
  • Faraz Mojab

Iranian Journal of Pharmaceutical Sciences, Vol. 21 No. 1 (2025), 21 January 2025 , Page 410-418
https://doi.org/10.22037/ijps.v21i1.47937 Published: 2025-09-23

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Abstract

Anxiety disorders are prevalent worldwide, significantly impacting various aspects of patients’ lives. The use of Salvia species in ethnobotanical medicine has been well documented, with applications as diuretics, analgesics, anti-hyperhidrosis agents, laxatives, antipyretics, and antitussives. Among these, Salvia hypoleuca, an endemic plant in Iran, is recognized for its tonic, carminative, digestive, antispasmodic, anti-inflammatory, antioxidant, antimicrobial, and anti-nociceptive properties. The objectives of this study were to assess the anxiolytic effects of S. hypoleuca ethanolic extract and its potential neurotoxicity using established pharmacological models in mice. Animals were randomly allocated into five groups: one control group, three groups underwent treatment that received oral doses of S. hypoleuca at 30, 100, and 300 mg/kg, and a positive control group given diazepam at 10 mg/kg. Behavioral evaluations were performed using the light/dark test (LDT) and the elevated plus maze (EPM) tests. To evaluate potential neurotoxic effects, open-field and rotarod tests were also performed. The results specified that S. hypoleuca extract at doses of 30 and 100 mg/kg significantly enhanced entries and time spent in the open arms of the EPM, suggesting anxiolytic effects. In the LDT, the 30 mg/kg dose notably increased the time spent in the light box. However, the rotarod test showed a slight decrease in latency to fall at both 30 and 300 mg/kg doses, indicating possible motor impairment at higher concentrations. Open-field analysis revealed significant reductions in total distance moved and velocity at 30 and 300 mg/kg doses, suggesting potential locomotor suppression.

Additionally, the total phenolic and total flavonoid contents of S. hypoleuca ethanolic extract were measured as 47.26 ± 2.87mg GAE/g DW and 31.73 ± 5.38 mgRE/g DW, respectively. In conclusion, our efforts suggest that oral administration of S. hypoleuca extract exhibits anxiolytic effects in mice, as demonstrated by improved performance in the EPM and LDT. However, the observed locomotor impairment at higher doses warrants further investigation to determine the optimal therapeutic dose and potential safety concerns.

Keywords:
  • Anxiety
  • flavonoids
  • Neurotoxicity
  • Phenolic compounds
  • Phytochemicals
  • Plant extract
  • Salvia hypoleuca
  • IJPS_Volume21_Issue1_Pages409-418

How to Cite

Talebi, M., Alinejad, R., Naderi, N., & Mojab, F. (2025). Anxiolytic and Potential Neurotoxic Effects of Salvia hypoleuca in Mice. Iranian Journal of Pharmaceutical Sciences, 21(1), 410–418. https://doi.org/10.22037/ijps.v21i1.47937
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References

Stein DJ, Lim CCW, Roest AM, de Jonge P, Aguilar-Gaxiola S, Al-Hamzawi A, et al. The cross-national epidemiology of social anxiety disorder: Data from the World Mental Health Survey Initiative. BMC Med 2017;15:1–21.

Chisholm D, Sweeny K, Sheehan P, Rasmussen B, Smit F, Cuijpers P, et al. Scaling-up treatment of depression and anxiety: A global return on investment analysis. Lancet Psychiatry 2016;3:415–24.

Talebi M, Kakouri E, Talebi M, Tarantilis PA, Farkhondeh T, İlgün S, et al. Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer’s disease. Expert Rev Neurother 2021;21.

Moffat JG, Vincent F, Lee JA, Eder J, Prunotto M. Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nat Rev Drug Discov 2017;16:531–43.

Ferrari A. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry 2022;9:137–50.

Arias D, Saxena S, Verguet S. Quantifying the global burden of mental disorders and their economic value. EClinicalMedicine 2022;54:101675.

Starcevic V. Benzodiazepines for anxiety disorders: maximising the benefits and minimising the risks. Advances in Psychiatric Treatment 2012;18:250–8.

Penninx BW, Pine DS, Holmes EA, Reif A. Anxiety disorders. Lancet 2021;397:914–27.

Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus anti-depressants in anxiety disorders: A systematic review and meta-analysis. Psychother Psychosom 2013;82:355–62.

Talebi M, Ayatollahi SA, As’Habi MA, Kobarfard F, Khoramjouy M, Boroujeni FN, et al. Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer’s disease. Heliyon 2025;11:e42412.

Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A. Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. European Neuropsychopharmacology 2011;21:841–60.

Ortiz-Mendoza N, Zavala-Ocampo LM, Martínez-Gordillo MJ, Eva González-Trujano M, Basurto Peña FA, Bazany-Rodríguez IJ, et al. Anti-nociceptive and anxiolytic-like effects of a neo-clerodane diterpene from Salvia semiatrata aerial parts. Pharm Biol 2020;58:620–9.

Nickavar B, Mojab F, Asgarpanah J. Volatile composition of the essential oil of Salvia hypoleuca Benth. International Journal of Aromatherapy 2005;15:51–3.

Esfahani HM, Amirshahrokhi K, Boroujeni HB, Dehpour A, Miran M. Anti-Anxiety Effect of Salvia hypoleuca. Research Journal of Pharmacognosy (RJP) 2020;7:1–4.

Sonboli A, Salehi P, Gharehnaghadeh S. Chemical variability in the essential oil composition of Salvia hypoleuca, an endemic species from Iran. Journal of Essential Oil Research 2016;28:421–7.

Imanshahidi M, Hosseinzadeh H. The pharmacological effects of Salvia species on the central nervous system. Phytotherapy Research 2006;20:427–37.

Lopresti AL. Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects. Drugs in R and D 2017;17:53–64.

Abdelhalim A, Hanrahan J. Biologically active compounds from Lamiaceae family: Central nervous system effects. Studies in Natural Products Chemistry 2021;68:255–315.

Nickavar B, Abolhasani L, Izadpanah H. α-Amylase Inhibitory Activities of Six Salvia Species. Iran J Pharm Res 2008; 7: 297-303.

Asghari B, Mafakheri S, Ghorbani Nohooji M. Evaluation of phytochemical, antioxidant and enzymatic inhibitory content of extracts obtained with different solvents from Salvia hypoleuca Benth. Eco-Phytochemical Journal of Medicinal Plants 2022;9:93–109.

Eidi A, Parivar K, Mazouji A, Akhtari Z. Anti-nociceptive effects of essential oil of Salvia hypoleuca L. in mice. Medical Science Journal of Islamic Azad Univesity - Tehran Medical Branch 2006;16:165–9.

Gharehbagh HJ, Ebrahimi M, Dabaghian F, Mojtabavi S, Hariri R, Saeedi M, et al. Chemical composition, cholinesterase, and α-glucosidase inhibitory activity of the essential oils of some Iranian native Salvia species. BMC Complement Med Ther 2023;23:184.

Shekarchi M, Hajimehdipoor H, Saeidnia S, Gohari AR, Hamedani MP, Hajimehdipoor H. Comparative study of rosmarinic acid content in some plants of Labiatae family n.d.:29.

Saeidnia S, Ghamarinia M, Gohari AR, Shakeri A. Terpenes From the Root of Salvia hypoleuca Benth. Daru 2012; 20.

Askari SF, Avan R, Tayarani-Najaran Z, Sahebkar A, Eghbali S. Iranian Salvia species: A phytochemical and pharmacological update. Phytochemistry 2021; 183: 112619.

Gabbas Z El, Bezza K, Laadraoui J, Makbal R, Aboufatima R, Chait A. Salvia officinalis induces antidepressant-like effect, anxiolytic activity and learning improvement in hippocampal lesioned and intact adult rats. Bangladesh J Pharmacol 2018;13:367–78.

Rabbani M, Sajjadi SE, Jafarian A, Vaseghi G. Anxiolytic effects of Salvia reuterana Boiss. on the elevated plus-maze model of anxiety in mice. J Ethnopharmacol 2005;101:100–3.

Herrera-Ruiz M, García-Beltrán Y, Mora S, Díaz-Véliz G, Viana GSB, Tortoriello J, et al. Anti-depressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans. J Ethnopharmacol 2006;107:53–8.

Lin YS, Peng WH, Shih MF, Cherng JY. Anxiolytic effect of an extract of Salvia miltiorrhiza Bunge (Danshen) in mice. J Ethnopharmacol 2021;264.

Naderi N, Akhavan N, Ahari FA, Zamani N, Kamalinejad M, Shokrzadeh M, et al. Effects of Hydroalcoholic Extract from Salvia verticillata on Pharmacological Models of Seizure, Anxiety and Depression in Mice. Iran J Pharm Res 2011;10:535.

Jahani R, Behzad S, Saffariha M, Toufan Tabrizi N, Faizi M. Sedative-hypnotic, anxiolytic and possible side effects of Salvia limbata C. A. Mey. Extracts and the effects of phenological stage and altitude on the rosmarinic acid content. J Ethnopharmacol 2022;282:114630.

Braida D, Capurro V, Zani A, Rubino T, Viganò D, Parolaro D, et al. Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents. Br J Pharmacol 2009;157:844.

Talebi M, Oskouie AA, Mahboubi A, Khani M, Mojab F. Analysis of Eremostachys hyoscyamoides essential oil composition and assessing the antibacterial and antioxidant properties of the ethanol extract. Heliyon 2024:e38389.

Pérez M, Dominguez-López I, Lamuela-Raventós RM. The Chemistry Behind the Folin–Ciocalteu Method for the Estimation of (Poly)phenol Content in Food: Total Phenolic Intake in a Mediterranean Dietary Pattern. J Agric Food Chem 2023;71:17543–53.

Faizi M, Khazaee R, Mojab F, Jahani R. Psychopharmacological assessment of antidepressant-like, anxiolytic, and sedative-hypnotic effects of Tilia platyphyllos Scop. extract using experimental animal models: Antidepressant-like, anxiolytic, and sedative-hypnotic properties of Tilia platyphyllos. Iranian Journal of Pharmaceutical Sciences 2022;18:116–27.

Jahani R, Mojab F, Mahboubi A, Nasiri A, Tahamtani A, Faizi M. An In-Vivo Study on Anticonvulsant, Anxiolytic, and Sedative-Hypnotic Effects of the Polyphenol-Rich Thymus Kotschyanus Extract; Evidence for the Involvement of GABAA Receptors. Iran J Pharm Res 2019;18:1456.

Jones SK, McCarthy DM, Vied C, Stanwood GD, Schatschneider C, Bhide PG. Transgenerational transmission of aspartame-induced anxiety and changes in glutamate-GABA signaling and gene expression in the amygdala. Proc Natl Acad Sci U S A 2022;119.

Shafaghi B, Naderi N, Tahmasb L, Kamalinejad M. Anxiolytic Effect of Echium amoenum L. in Mice. Iranian Journal of Pharmaceutical Research 2002 1:1 2002;1:37–41.

Caesar LK, Cech NB. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Nat Prod Rep 2019;36:869–88.

Motaghi S, Teimouri M. Investigation of anxiolytic and hypnotic effects of aqueous and hydroalcoholic extracts of Salvia officinalis in adult mice. Iranian Journal of Physiology and Pharmacology 2018;2:151–144.

Piątczak E, Owczarek A, Lisiecki P, Gonciarz W, Kozłowska W, Szemraj M, et al. Identification and quantification of phenolic compounds in Salvia cadmica Boiss. and their biological potential. Ind Crops Prod 2021;160:113113.

Zhumaliyeva G, Zhussupova A, Zhusupova GE, Błońska-Sikora E, Cerreto A, Omirbekova N, et al. Natural Compounds of Salvia L. Genus and Molecular Mechanism of Their Biological Activity. Biomedicines 2023;11:3151.

Lu Y, Yeap Foo L. Polyphenolics of Salvia—a review. Phytochemistry 2002;59:117–40.

Ayoub IM, George MY, Menze ET, Mahmoud M, Botros M, Essam M, et al. Insights into the neuroprotective effects of Salvia officinalis L. and Salvia microphylla Kunth in the memory impairment rat model. Food Funct 2022;13:2253–68.

Ebrahimi M, Jazayeri Gharehbagh H, Dabaghian F, Mojtabavi S, Khademian S, Saeedi M, et al. Salvia mirzayanii and Salvia hypoleuca Essential Oils: Chemical Composition, Alpha-Glucosidase Inhibitory, and Synergistic Effects of Selected Components. Jundishapur J Nat Pharm Prod 2024;19.

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