Cholinergic cognitive enhancer effect of Salvia triloba L. essential oil inhalation in rats

Abstract

Objective: Current treatment of Alzheimer’s disease is provided by cholinesterase inhibitors. Salvia triloba L. (syn. Salvia fruticosa Mill.), a species mostly consumed as refreshing herbal tea in traditional medicine, is rich in 1,8-cineole that is known to have cholinesterase inhibiting effects. In this study, we investigated cognitive enhancer effects of S. triloba essential oil inhalation on healthy control rats and rats with scopolamine induced memory impairment. Materials and Methods: S. triloba samples from different geographical locations of Turkey were hydro-distilled and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). The optimum sample with the highest 1,8-cineole and lowest camphor, α-thujone and β-thujone content was selected. In vitro cholinergic and antioxidant potentials of the selected essential oil were calculated. Cognitive enhancer and anti-amnestic effects of the inhaled essential oil on rats were assessed by means of Morris water maze. The bioavailability of 1,8-cineole in blood of rats was measured by GC-MS. Results: The group that inhaled S. triloba significantly outperformed control group, namely faster achieving peak escape latency performance in Morris water maze. However, S. triloba inhalation failed to restore scopolamine induced learning impairment. Conclusion: In this study, we report positive effects of inhaling S. triloba essential oil as a complementary treatment for supporting cognitive functions.

Keywords

• Cognitive enhancers
• Essential oil
• Gas chromatography
• 1
• 8-Cineole
• Antioxidants
• Morris water maze

References

1. Association As. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 2018; 14:367-429. doi: 10.1016/j. jalz.2018.02.001.
2. Wilson RS, Segawa E, Boyle PA, Anagnos SE, Hizel LP, Bennett DA. The natural history of cognitive decline in Alzheimer’s disease. Psychol Aging 2012; 27:1008-17. doi: 10.1037/ a0029857.
3. Hampel H, Mesulam M-M, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 2018; 141:1917-33. doi: 10.1093/brain/awy132.
4. Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ. Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 2014; 5:88. doi: 10.3389/ fgene.2014.00088.
5. Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies. Neurosci Biobehav R 2010; 34:1307-50. https://doi.org/10.1016/j.neubiorev.2010.04.001.
6. Yuede CM, Dong H, Csernansky JG. Anti-dementia drugs and hippocampal-dependent memory in rodents. Behav Pharmacol 2007; 18:347-63. doi: 10.1097/FBP.0b013e3282da278d.
7. esavage JA, Mumenthaler MS, Taylor JL, Friedman L, O’Hara R, Sheikh J, et al. Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 2002; 59:123- 5. doi: 10.1212/WNL.59.1.123.
8. Kukolja J, Thiel CM, Fink GR. Cholinergic stimulation enhances neural activity associated with encoding but reduces neural activity associated with retrieval in humans. J Neurosci 2009; 29:8119-28. doi: 10.1523/JNEUROSCI.0203-09.2009.

9. Grön G, Kirstein M, Thielscher A, Riepe MW, Spitzer M. Cholinergic enhancement of episodic memory in healthy young adults. Psychopharmacology (Berl) 2005; 182:170-9. doi: 10.1007/s00213.005.0043-2.
10. FitzGerald DB, Crucian GP, Mielke JB, Shenal BV, Burks D, Womack KB, et al. Effects of donepezil on verbal memory after semantic processing in healthy older adults. Cogn Behav Neurol 2008; 21:57 64. doi: 10.1097/WNN.0b013e3181799df1.
11. Repantis D, Laisney O, Heuser I. Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 2010; 61:473- 81. doi: 10.1016/j.phrs.2010.02.009.
12. Chuah LY, Chong DL, Chen AK, et al. Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation. Sleep 2009; 32:999-1010. doi: 10.1093/sleep/32.8.999.
13. Sofuoglu M, Herman AI, Li Y, Waters AJ. Galantamine attenuates some of the subjective effects of intravenous nicotine and improves performance on a Go No-Go task in abstinent cigarette smokers: a preliminary report. Psychopharmacology (Berl) 2012; 224:413-20. doi: 10.1007/s00213.012.2763-4.
14. Perry NS, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 2003; 75:651-9. doi: 10.1016/S0091-3057(03)00108-4.
15. Kalaycıoğlu Z, Uzaşçı S, Dirmenci T, Erim FB. α-Glucosidase enzyme inhibitory effects and ursolic and oleanolic acid contents of fourteen Anatolian Salvia species. J Pharm Biomed Anal 2018; 155:284-7. doi: 10.1016/j.jpba.2018.04.014.
16. Sen Utsukarci B, Gurdal B, Bilgin M, Satana D, Demirci B, Tan N, et al. Biological activities of various extracts from Salvia cassia Sam. ex Rech. f. and chemical composition of its most active extract. Rec Nat Prod 2019; 13:24-36. doi: 10.25135/ rnp.68.18.02.090.
17. Bagci E, Akbaba E, Maniu C, Ungureanu E, Hritcu L. Evaluation of antiamnesic activity of Salvia multicaulis essential oil on scopolamine-induced amnesia in rats: in vivo and in silico approaches. Heliyon 2019; 5:e02223. doi: 10.1016/j.heliyon.2019.e02223.
18. Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L.(sage) leaves on memory retention and its interaction with the cholinergic system in rats. Nutrition 2006; 22:321-6. doi: 10.1016/j.nut.2005.06.010.
19. Er M, Tugay O, Özcan MM, Ulukuş D, Fahad A-J. Biochemical properties of some Salvia L. species. Environ Monit Assess 2013; 185:5193-8. doi: 10.1007/s10661.012.2935-z.
20. Ghorbani A, Esmaeilizadeh M. Pharmacological properties of Salvia officinalis and its components. JTCM 2017; 7:433-40. doi: 10.1016/j.jtcme.2016.12.014.
21. Seker Karatoprak G, Goger F, Celik I, Budak U, Akkol EK, Aschner M. Phytochemical profile, antioxidant, antiproliferative, and enzyme inhibition-docking analyses of Salvia ekimiana Celep & Dogan. S Afr J Bot 2022; 146:36-47. doi: 10.1016/j.sajb.2021.09.033.
22. Kupeli Akkol E, Goger F, Kosar M, Baser KH. Phenolic composition and biological activities of Salvia halophila and Salvia virgata from Turkey. Food Chem 2008; 108:942-9. doi: 10.1016/j.foodchem.2007.11.071.
23. Xu J, Wei K, Zhang G, et al. Ethnopharmacology, phytochemistry, and pharmacology of Chinese Salvia species: A review. J Ethnopharmacol 2018; 225:18-30. doi: 10.1016/j. jep.2018.06.029.
24. Bahadori MB, Dinparast L, Zengin G, et al. Functional components, antidiabetic, anti-Alzheimer’s disease, and antioxidant activities of Salvia syriaca L. Int J Food Prop 2017; 20:1761-72. doi: 10.1080/10942.912.2016.1218893.
25. Savelev SU, Okello EJ, Perry EK. Butyryl‐and acetylcholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res 2004; 18:315-24. doi: 10.1002/ptr.1451.
26. Şenol FS, Orhan IE, Erdem SA, Kartal M, Sener B, Kan Y, et al. Evaluation of cholinesterase inhibitory and antioxidant activities of wild and cultivated samples of sage (Salvia fruticosa) by activity guided fractionation. J Med Food 2011; 14:1476-83. doi: 10.1089/jmf.2010.0158.
27. Benny A, Thomas J. Essential oils as treatment strategy for Alzheimers disease: Current and future perspectives. Planta Med 2019; 85:239-48. doi: 10.1055/a-0758-0188
28. Satou T, Hanashima Y, Mizutani I, Koike K. The effect of inhalation of essential oil from Rosmarinus officinalis on scopolamine-induced Alzheimer’s type dementia model mice. Flavour Fragr J 2018; 33:230-4. doi: 10.1002/ffj.3435.
29. Aydın D, Katar N, Katar D, Olgun M. Determination of the effect of different drying temperatures on the content and chemical composition of essential oil of Greek sage (Salvia fruticosa Mill.= Salvia triloba L.). International Journal of Agricultural Wildlife Sciences 2019; 5:103-9. doi: 10.24180/ ijaws.450195.
30. Rao PS, Kalva S, Yerramilli A, Mamidi S. Free radicals and tissue damage: Role of antioxidants. Free radicals and antioxidants 2011; 1:2-7. doi: 10.5530/ax.2011.4.2.
31. Kim GH, Kim JE, Rhie SJ, Yoon S. The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 2015; 24:325- 40. doi: 10.5607/en.2015.24.4.325.
32. Orhan I, Kartal M, Naz Q, et al. Antioxidant and anticholinesterase evaluation of selected Turkish Salvia species. Food Chem 2007; 103:1247-54. doi: 10.1016/j. foodchem.2006.10.030.
33. Zhu X, Raina AK, Lee H-g, Casadesus G, Smith MA, Perry G. Oxidative stress signalling in Alzheimer’s disease. Brain Res 2004; 1000:32-9. doi: 10.1016/j.brainres.2004.01.012.
34. Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012; 69:836-41. doi: 10.1001/ archneurol.2012.85.
35. Marucci G, Buccioni M, Dal Ben D, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology 2021;190:108352. doi: 10.1016/j.neuropharm.2020.108352.
36. Barak TH, Bölükbaş E, Bardakcı H. Evaluation of marketed rosemary essential oils (Rosmarinus officinalis L.) in terms of European Pharmacopoeia 10.0 Criteria. Turk J Pharm Sci 2023; 20:253-60. doi: 10.4274/tjps.galenos.2022.78010
37. Servi H, Demir U, Servi EY, Gundogdu B, Barak TH. Antiproliferative and antibacterial activities of four commercial essential oil samples from Boswellia carteri, B. serrata, and two chemotypes of Canarium luzonicum. J Essent Oil-Bear Plants 2023;26:79-94. doi: 10.1080/0972060X.2023.216.5167
38. İnan Y, Kurt-Celep I, Akyüz S, Barak TH, Celep E, Yesilada E. An investigation on the enzyme inhibitory activities, phenolic profile and antioxidant potentials of Salvia virgata Jacq. S Afr J Bot 2021;143:350-8. doi: 10.1016/j.sajb.2020.12.007.
39. Bardakci H, Cevik D, Barak TH, Gozet T, Kan Y, Kirmizibekmez H. Secondary metabolites, phytochemical characterization and antioxidant activities of different extracts of Sideritis congesta PH Davis et Hub.-Mor. Biochem Syst Ecol 2020; 92:104120. doi: 10.1016/j.bse.2020.104120.
40. Selçuk SS, Ozek T, Özek G, Yur, et al. The leaf and the gall volatiles of salvia fruticosa miller from Turkey: Chemical composition and biological activities. Rec Nat Prod 2021; 15:10-24. doi: 10.25135/rnp.185.20.03.1579.
41. Gali-Muhtasib H. Anticancer and medicinal properties of essential oil and extracts of East Mediterranean sage (salvia triloba). In: Khan MTH, Ather A, eds. Lead Molecules from Natural Products: Discovery and New Trends. Advances in Phytomedicine. Amsterdam: Elsevier Science, 2006: 171,180.
42. Németh ÉZ, Nguyen HT. Thujone, a widely debated volatile compound: What do we know about it? Phytochem Rev 2020; 19:405-23. doi: 10.1007/s11101.020.09671-y.
43. Smith MA, Harris PL, Sayre LM, Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A 1997; 94:9866-8. doi: 10.1073/pnas.94.18.986.
44. Wong KK-K, Ho MT-W, Lin HQ, et al. Cryptotanshinone, an acetylcholinesterase inhibitor from Salvia miltiorrhiza, ameliorates scopolamine-induced amnesia in Morris water maze task. Planta Med 2010; 76:228-34. doi: 10.1055/s- 0029.118.6084.
45. Dinel A-L, Lucas C, Guillemet D, Layé S, Pallet V, Joffre C. Chronic supplementation with a mix of salvia officinalis and salvia lavandulaefolia improves Morris water maze learning in normal adult C57Bl/6J Mice. Nutrients 2020; 12:1777. doi: 10.3390/nu12061777.
46. Tildesley N, Kennedy D, Perry E, Ballard C, Wesnes K, Scholey A. Cognitive and mood effects of acute administration of Salvia lavandulaefolia (Spanish Sage) to healthy young volunteers. Physiol Behav 2005; 83:699-709. doi: 10.1016/ S0091-3057(03)00122-9.
47. Solari N, Hangya B. Cholinergic modulation of spatial learning, memory and navigation. Eur J Neurosci 2018;48:2199-230. doi: 10.1111/ejn.14089.
48. Makhaeva GF, Lushchekina SV, Boltneva NP, et al. 9-Substituted acridine derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors possessing antioxidant activity for Alzheimer’s disease treatment. Bioorg Med Chem 2017; 25:5981-94. doi: 10.1016/j.bmc.2017.09.028.
49. Garthe A, Kempermann, G. An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis. Front Neurosci 2013; 7:63. doi: 10.3389/fnins.2013.00063.