Protective effects of Pluchea lanceolata on dementia induced by omeprazole in experimental rats

Abstract

Omeprazole is the most commonly used proton pump inhibitor (PPI), a prospective cohort study reported that chronic use of PPI’s cause dementia. The present study aimed to evaluate the protective effect of hydro alcoholic extract of Pluchea lanceolata (HAEPL) on dementia induced by omeprazole in experimental rats. Total 42 trained rats were divided into 7 groups, each group with six rats. First group received normal food and water for 21 days. Three groups of animals treated with 20mg/kg of omeprazole for 7, 14 and 21 days respectively. Another three groups of animals received 400mg/kg of HAEPL + 20mg/kg of omeprazole for 7, 14 and 21 days respectively. Behavioural studies were conducted on 0th, 7th, 14th and 21st days of treatment by using actophotometer, elevated plus maze (EPM) and cook’s pole climbing apparatus. The next day of behaviour study respective group animals were sacrificed, brain was isolated for estimation of antioxidant, neurotransmitters and histopathological studies. Locomotor activity, number of entry into open arms and time taken to climb the poles were significantly reduced in 20 mg/kg of omeprazole treated rats whereas activity, learning, memory were restored in 400mg/kg of HAEPL treated rats with respect to duration of exposure. Alteration of antioxidant enzyme, neurotransmitter level and histopathological events were found with disease control rats which also corrected by the administration of 400mg/kg of HAEPL. Co-administration of P, lanceolata extract diminishes the progress of dementia caused by omeprazole and may be a potential corner stone in the treatment strategies for researchers and clinicians.

Keywords

• Omeprazole
• dementia
• Pluchea lanceolata
• antioxidants
• neurotransmitters

References

1. Alisky J. M. (2006). Neurotransmitter depletion may be a cause of dementia pathology rather than an effect. Medical hypotheses, 67(3), 556–560. https://doi.org/10.1016/j.mehy.2006.02.043
2. Casado, A., Encarnación López-Fernández, M., Concepción Casado, M., & de La Torre, R. (2008). Lipid peroxidation and antioxidant enzyme activities in vascular and Alzheimer dementias. Neurochemical research, 33(3), 450–458. https://doi.org/10.1007/s11064-007-9453-3.
3. Cook, L., & Weidley, E. (1957). Behavioral effects of some psychopharmacological agents. Annals of the New York Academy of Sciences, 66(3), 740–752. https://doi.org/10.1111/j.1749-6632.1957.tb40763.x
4. Cooksey, R., Kennedy, J., Dennis, M. S., Escott-Price, V., Lyons, R. A., Seaborne, M., & Brophy, S. (2020). Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK. PloS one, 15(9), e0237676. https://doi.org/10.1371/journal.pone.0237676
5. Ellman G. L. (1959). Tissue sulfhydryl groups. Archives of biochemistry and biophysics, 82(1), 70–77. https://doi.org/10.1016/0003-9861(59)90090-6
6. Gallagher M. (1997) Animal models of memory impairment. Philos Trans R Soc Lond B Biol Sci. 29;352(1362):1711-7. doi: 10.1098/rstb.1997.0153
7. Gloria Ortiz-Guerrero, Diana Amador-Muñoz, Carlos Alberto Calderón-Ospina, Daniel López-Fuentes, Mauricio Orlando Nava Mesa, "Proton Pump Inhibitors and Dementia: Physiopathological Mechanisms and Clinical Consequences", Neural Plasticity, vol. 2018, Article ID 5257285, 9 pages, 2018. https://doi.org/10.1155/2018/5257285
8. https://www.who.int/news-room/fact-sheets/detail/dementia 2 September 2021.

9. Jafarian, S., Ling, K. H., Hassan, Z., Perimal-Lewis, L., Sulaiman, M. R., & Perimal, E. K. (2019). Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats. Alzheimer's & dementia (New York, N. Y.), 5, 637–643. https://doi.org/10.1016/j.trci.2019.09.009
10. Kueper, J. K., Speechley, M., Lingum, N. R., & Montero-Odasso, M. (2017). Motor function and incident dementia: a systematic review and meta-analysis. Age and ageing, 46(5), 729–738. https://doi.org/10.1093/ageing/afx084
11. Kumar, R., Kumar, A., Nordberg, A., Långström, B., & Darreh-Shori, T. (2020). Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme-A plausible missing link for their association with incidence of dementia. Alzheimer's & dementia : the journal of the Alzheimer's Association, 16(7), 1031–1042. https://doi.org/10.1002/alz.12113
12. Ltoh, J., Nabeshima, T. & Kameyama, T. (1990). Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology 101, 27–33. https://doi.org/10.1007/BF02253713
13. Mæhre, H. K., Dalheim, L., Edvinsen, G. K., Elvevoll, E. O., & Jensen, I. J. (2018). Protein Determination-Method Matters. Foods (Basel, Switzerland), 7(1), 5. https://doi.org/10.3390/foods7010005
14. Makunts, T., Alpatty, S., Lee, K.C. et al. (2019) Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory. Sci Rep 9, 17280. https://doi.org/10.1038/s41598-019-53622-3
15. Marcus, D. L., Thomas, C., Rodriguez, C., Simberkoff, K., Tsai, J. S., Strafaci, J. A., & Freedman, M. L. (1998). Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease. Experimental neurology, 150(1), 40–44. https://doi.org/10.1006/exnr.1997.6750
16. Nakamura, S., Koshimura, K., Kato, T., Yamao, S., Iijima, S., Nagata, H., Miyata, S., Fujiyoshi, K., Okamoto, K., & Suga, H. (1984). Neurotransmitters in dementia. Clinical therapeutics, 7 Spec No, 18–34.
17. Novotny M, Klimova B and Valis M (2019) PPI Long Term Use: Risk of Neurological Adverse Events? Front. Neurol. 9:1142. doi: 10.3389/fneur.2018.01142
18. Ortiz-Guerrero, G., Amador-Muñoz, D., Calderón-Ospina, C. A., López-Fuentes, D., & Nava Mesa, M. O. (2018). Proton Pump Inhibitors and Dementia: Physiopathological Mechanisms and Clinical Consequences. Neural plasticity, 2018, 5257285. https://doi.org/10.1155/2018/5257285
19. Palash, M., Kumar, V., Kumar, S., Maurya, S.K., Nandi, M.K., & Damiki, L. (2013). A controversial medicinal plant ‘Rasna’: An overview. International Conference on Global Scenario of Traditional System of Medicine, Ayurveda, Agriculture and Education, 102–105.
20. Raju, A., & Sinchu, Y. (2018). Neuropharmacological study of Humboldtia vahliana Wight. Scholars Academic Journal of Pharmacy, 7(4), 171-183. DOI : 10.21276/sajp.2018.7.4.1
21. Schlumpf, M., Lichtensteiger, W., Langemann, H., Waser, P. G., & Hefti, F. (1974). A fluorometric micromethod for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of brain tissue. Biochemical pharmacology, 23(17), 2437–2446. https://doi.org/10.1016/0006-2952(74)90235-4
22. Soman, I., Mengi, S. A., & Kasture, S. B. (2004). Effect of leaves of Butea frondosa on stress, anxiety, and cognition in rats. Pharmacology, biochemistry, and behavior, 79(1), 11–16. https://doi.org/10.1016/j.pbb.2004.05.022
23. Wilson, R. S., Begeny, C. T., Boyle, P. A., Schneider, J. A., & Bennett, D. A. (2011). Vulnerability to stress, anxiety, and development of dementia in old age. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 19(4), 327–334. https://doi.org/10.1097/JGP.0b013e31820119da