Exploring The Anxiolytic and Neurobehavioral Benefits of Serratiopeptidase in Mice

Abdul Hameed, Younes; Naser, Ahmad

doi:10.21608/javs.2024.330246.1455

Exploring The Anxiolytic and Neurobehavioral Benefits of Serratiopeptidase in Mice

Document Type : Original Article

Authors

Younes Abdul hameed ¹
Ahmad Naser ²

¹ Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq

² Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq.

10.21608/javs.2024.330246.1455

Abstract

Serratiopeptidase exhibits therapeutic efficacy in a variety of disease models; in addition to its ability to mediate anti-inflammatory action, it is also responsible for regulating several biological activities by targeting different signaling pathways. Our study aimed to evaluate the central nervous effect of serratiopeptidase on neurobehavioral activities and to eliminate anxiety manifestations in mice. Male mice were subjected to neurobehavioral tests, including open field, negative geotaxis, head poking, and swimming tests, in addition to methods of screening for antianxiety, such as elevated pulse maze and light-dark box tests, after one hour of serratiopeptidase at 5, 10, and 20 mg/kg orally. Serratiopeptidase at 20 mg/kg produced a significant increase in the number of squares cut and rearing compared to the control group. Serratiopeptidase at 5, 10, and 20 mg/kg resulted in a decrease in the time required to correct the position of mice in comparison with the control group in negative geotaxis, and there was an increase in the number of stockings compared with the control group. Serratiopeptidase (20 mg/kg) significantly increased the duration of time spent in the open arm and significantly decreased the amount of time spent in the closed arm compared with the control group and the light-dark box test. Serratiopeptidase at 20 mg/kg significantly increased the time spent on the light side of mice and significantly decreased the time spent on the dark side. Serratiopeptidase at 20 mg/kg demonstrated superior effects to the group treated with sertraline in reducing anxiety-like behavior in both tests. In conclusion, serratiopeptidase has a stimulatory effect on the central nervous system, and a high dose may produce anxiolytic-like effects.

Keywords

Main Subjects

Pharmacology and toxicology

References

AL-AWADHI, R. M., KILANY, O. E., ABDALLAH, O. M., NAGUIB, F. M., and NAGEH, H., 2024. Neuroprotective Effects of Grape Seed Extract against Cadmium Toxicity in Broilers. Journal of Applied Veterinary Sciences, 9(3), 86–101. DOI: 10.21608/javs.2024.293367.1344

AL-JUMAA, Z. M., AL-TAEE, S. K., JABER, M. T., and RAHHAWI, A. M., 2024. Histopathological Alteration and Molecular Detection of Gills Rot Fungus in Carp Fish. Journal of Applied Veterinary Sciences, 9(4), 54–59. DOI: 10.21608/javs.2024.301499.1373

AL-SHALCHI, R. F., and MOHAMMAD, F. K., 2024. Adverse neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with statins. Veterinary World, 17(1), 82. https://doi.org/10.14202/vetworld.2024.82-88

ALBADRANY, Y. M., NASER, A. S., and HASAN, M. M., 2021. Study the analgesic effect of diclofenac and silymarin coadministration in chicks. Iraqi Journal of Veterinary Sciences, 35(5), 25-31. https://doi.org/10.33899/ijvs.2021.127065.1453

ALBADRANY, Y., and NASER, A., 2020 . Coenzyme Q10 coadministration with diclofenac augmented impaired renal function in broiler chickens (Gallus gallus domesticus). Veterinary World, 13(4), 642. https://doi.org/10.14202/vetworld.2020.642-648

AZZAM, S. M., RAHMAN, A. A. S. A., AHMED-FARID, O. A., EL-WAFA, W. M. A., and SALEM, G. E. M., 2023 . Lipopolysaccharide induced neuroprotective effects of bacterial protease against Alzheimer’s disease in male Wistar albino rats. International Journal of Biological Macromolecules, 230, 123260. https://doi.org/10.1016/j.ijbiomac.2023.123260

BAKARE, A. O., and OWOYELE, B. V., 2021. Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats. Scientific Reports, 11(1), 289. https://doi.org/10.1038/s41598-020-79421-9

BASHAR, Q. M., and ALBADRANY, Y. M. 2022. Evaluation of the Antipyretic, Analgesic, and Anti-inflammatory Effects of Pregabalin in Chicks. Egyptian Journal of Veterinary Sciences, 53(3), 323–328. https://doi.org/10.21608/ejvs.2022.131986.1336

BHALLA, S., MEHAN, S., KHAN, A., and REHMAN, M. U., 2022. Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions. Neuroscience and Biobehavioral Reviews, 142, 104896. https://doi.org/10.1016/j.neubiorev.2022.104896

BOURIN, M., and HASCOËT, M., 2003. The mouse light/dark box test. European Journal of Pharmacology, 463(1–3), 55–65. https://doi.org/10.1016/S0014-2999(03)01274-3

BURNE, T. H. J., JOHNSTON, A. N. B., MCGRATH, J. J., and MACKAY-SIM, A., 2006. Swimming behaviour and post-swimming activity in Vitamin D receptor knockout mice. Brain Research Bulletin, 69(1), 74–78. https://doi.org/10.1016/j.brainresbull.2005.10.014

CRAWLEY, J. N. 1999. Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Research, 835(1), 18–26. https://doi.org/10.1016/S0006-8993(98)01258-X

DHIMAN, A., and PUROHIT, R., 2023. Targeting tachykinin peptides involved in viral infections through in silico approach: Screening the unforeseen potency of serratiopeptidase. Journal of Molecular Liquids, 392, 123504. https://doi.org/10.1016/j.molliq.2023.123504

FC, F., KJP, M., MMM, C., TL, F., BBI, T., and BN, V., 2024. Effects of Aqueous and Ethanolic Extracts of Ginger (Zingiber Officinale) Rhizome on Serum Progesterone Level and Markers of Oxidative Stress in African Giant Rat (Cricetomys Gambianus) in Captivity. Journal of Applied Veterinary Sciences, 9(3), 11-18. DOI: 10.21608/javs.2024.278828.1326

FIRDAUS, Z., KUMAR, D., SINGH, S. K., and SINGH, T. D., 2022. Centella asiatica alleviates AlCl3-induced cognitive impairment, oxidative stress, and neurodegeneration by modulating cholinergic activity and oxidative burden in rat brain. Biological Trace Element Research, 200(12), 5115–5126. https://doi.org/10.1007/s12011-021-03083-5

HOSSEINI, S. B., AZIZI, M., NOJOUMI, S. A., and VALIZADEH, V., 2024. An up-to-date review of biomedical applications of serratiopeptidase and its biobetter derivatives as a multi-potential metalloprotease. Archives of Microbiology, 206(4), 180. https://doi.org/10.1007/s00203-024-03889-6

JADHAV, S. B., SHAH, N., RATHI, A., RATHI, V., and RATHI, A., 2020. Serratiopeptidase: Insights into the therapeutic applications. Biotechnology Reports, 28, e00544. https://doi.org/10.1016/j.btre.2020.e00544

JAGANNATHAN, H., THOTA, A., B. KUMARAPPA, A. K., and KISHORE, G., 2020. A comparative study of aceclofenac versus etoricoxib in the management of acute low back pain in a tertiary care hospital. Journal of Drug Assessment, 9(1), 60–65. https://doi.org/10.1080/21556660.2020.1734008

KENWOOD, M. M., KALIN, N. H., and BARBAS, H., 2022. The prefrontal cortex, pathological anxiety, and anxiety disorders. Neuropsychopharmacology, 47(1), 260–275. https://doi.org/10.1038/s41386-021-01109-z

LA-VU, M., TOBIAS, B. C., SCHUETTE, P. J., and ADHIKARI, A., 2020. To approach or avoid: an introductory overview of the study of anxiety using rodent assays. Frontiers in Behavioral Neuroscience, 14, 145. https://doi.org/10.3389/fnbeh.2020.00145

MOHAMMAD, F. K. 1986. Assessment Of Behavioral, Neurochemical And Developmental Effects In Developing Rats Following In Utero Exposure To Non-Teratogenic Levels Of 2, 4-D And 2, 4, 5-T (Herbicides, Ontogeny). 8(5):551-60. PMID: 3785517

MOTZ, B. A., and ALBERTS, J. R., 2005. The validity and utility of geotaxis in young rodents. Neurotoxicology and Teratology, 27(4), 529–533. https://doi.org/10.1016/j.ntt.2005.06.005

NAIK, S., KATARIYA, R., SHELKE, S., PATRAVALE, V., UMEKAR, M., KOTAGALE, N., and TAKSANDE, B., 2023. Nattokinase prevents β-amyloid peptide (Aβ1-42) induced neuropsychiatric complications, neuroinflammation and BDNF signalling disruption in mice. European Journal of Pharmacology, 952, 175821. https://doi.org/10.1016/j.ejphar.2023.175821

NASER, A. S., and ALBADRANY, Y. M., 2024. Evaluation of the therapeutic effects of serratiopeptidase in chicks. Macedonian Veterinary Review, 47(2), 115-122.https://doi.org/10.2478/macvetrev-2024-0021

NASER, A. S., and ALBERIFKANI, N. M., 2023. Assessment of anxiolytic-like effects of acute and chronic treatment of flurbiprofen in murine. Journal of Ideas in Health, 6(1), 814–819. https://doi.org/10.47108/jidhealth.Vol6.Iss1.268

NASER, A., ALBADRANY, Y., and SHAABAN, K. A., 2021 . Methods of Pain Assessment in Chicks as a Model. Egyptian Journal of Veterinary Sciences, 52(2), 241–249. https://doi.org/10.21608/ejvs.2021.64605.1219

OHKUMA, S., and KATSURA, M., 2001. Nitric oxide and peroxynitrite as factors to stimulate neurotransmitter release in the CNS. Progress in Neurobiology, 64(1), 97–108. https://doi.org/10.1016/S0301-0082(00)00041-1

RODGERS, R. J., and DALVI, A., 1997. Anxiety, defence and the elevated plus-maze. Neuroscience and Biobehavioral Reviews, 21(6), 801–810. https://doi.org/10.1016/S0149-7634(96)00058-9

SAHA, S., BUTTARI, B., PANIERI, E., PROFUMO, E., and SASO, L., 2020. An overview of Nrf2 signaling pathway and its role in inflammation. Molecules, 25(22), 5474. https://doi.org/10.3390/molecules25225474

SAXENA, P., SELVARAJ, K., KHARE, S. K., and CHAUDHARY, N., 2022. Superoxide dismutase as multipotent therapeutic antioxidant enzyme: Role in human diseases. Biotechnology Letters, 1–22. https://doi.org/10.1007/s10529-021-03200-3

SCHAPIRO, S., SALAS, M., and VUKOVICH, K., 1970. Hormonal effects on ontogeny of swimming ability in the rat: assessment of central nervous system development. Science, 168(3927), 147–151. https://doi.org/10.1126/science.168.3927.147

STANFORD, S. C. 2007. The open field test: reinventing the wheel. Journal of Psychopharmacology, 21(2), 134–135. https://doi.org/10.1177/0269881107073199

TELEANU, R. I., NICULESCU, A.-G., ROZA, E., VLADÂCENCO, O., GRUMEZESCU, A. M., and TELEANU, D. M., 2022. Neurotransmitters—key factors in neurological and neurodegenerative disorders of the central nervous system. International Journal of Molecular Sciences, 23(11), 5954. https://doi.org/10.3390/ijms23115954

TIWARI, M. 2017. The role of serratiopeptidase in the resolution of inflammation. Asian Journal of Pharmaceutical Sciences, 12(3), 209–215. https://doi.org/10.1016/j.ajps.2017.01.003

YARDIMCI, A., ERTUGRUL, N. U., OZGEN, A., OZBEG, G., OZDEDE, M. R., ERCAN, E. C., and CANPOLAT, S., 2023. Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult male and female rats: An HPLC-ECD study. Neuroscience Letters, 806, 137245. https://doi.org/10.1016/j.neulet.2023.137245