Protective effect of Piper cubeba L.f. extract and lignan fraction against cognitive impaired rat models
DOI:
https://doi.org/10.31117/neuroscirn.v8i4.445Keywords:
Cognitive, Inflammation, Oxidative stressAbstract
This study aimed to examine the neuroprotective effect of Piper cubeba on cognitive impairment models using two induction methods: electroconvulsive shock (ECS) and scopolamine (SCO). For each model, male Sprague-Dawley rats were divided into five groups: P. cubeba 96% ethanol extract (PCE), P. cubeba lignan-rich fraction (LRF), citicoline (C; positive control), ECS/SCO control, and normal control (NO). The test substances were administered p.o. for 14 days, after which the rats except those in the NO group, were treated with ECS or SCO, depending on the model. Cognitive function was evaluated using the Morris Water Maze (MWM). Biochemical examinations were performed on the hippocampus and cerebral cortex, including lipid peroxidase inhibition, superoxide dismutase (SOD) and catalase (CAT) activity, and levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). The results showed that pretreatment with PCE and LRF improved cognitive function in ECS- and SCO-treated rats, with significantly lower escape latencies than those of the control groups (p<0.05). Moreover, PCE and LRF significantly increased hippocampal CAT and SOD activity compared with the ECS or SCO groups (p<0.05). PCE and LRF also significantly suppressed inflammatory cytokine levels (TNF-α and IL-1β) in the hippocampus and cerebral cortex, with levels significantly lower than those in the control groups (p<0.05). Overall, the extract and lignan fraction of P. cubeba improved cognitive function in both models, potentially through antioxidant and anti-inflammatory actions in the hippocampus and cerebral cortex.
Downloads
References
Banasr, M., Valentine, G. W., Li, X., Gourley, S. L., Taylor, J. R., & Duman, R. S. (2007). Chronic Unpredictable Stress Decreases Cell Proliferation in the Cerebral Cortex of the Adult Rat. Biological Psychiatry, 62(5), 496–504. https://doi.org/10.1016/j.biopsych.2007.02.006
Bogdanov, P., Sampedro, J., Sol, C., Sim, O., Russo, C., Varela-sende, L., Sim, R., & Hern, C. (2018). Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration. International Journal of Molecular Sciences, 19(8), 2458. https://doi.org/10.3390/ijms19082458
Bos, R., Woerdenbag, H. J., Kayser, O., Quax, W. J., Ruslan, K., & Elfami, E. (2007). Essential Oil Constituents of Piper cubeba L. fils. from Indonesia. Journal of Essential Oil Research, 19(1), 14–17. https://doi.org/10.1080/10412905.2007.9699217
Busnello, J. V., Leke, R., Oses, J. P., Feier, G., Bruch, R. S., Quevedo, J., Kapczinski, F., Souza, D. O., & Cruz Portela, L. V. (2006). Acute and chronic electroconvulsive shock in rats: Effects on peripheral markers of neuronal injury and glial activity. Life Sciences, 78(26), 3013–3017. https://doi.org/10.1016/j.lfs.2005.11.028
D’Hooge, R., & De Deyn, P. P. (2001). Applications of the Morris water maze in the study of learning and memory. Brain Research Reviews, 36(1), 60–90. https://doi.org/10.1016/S0165-0173(01)00067-4
Dimopoulos, N., Piperi, C., Salonicioti, A., Mitropoulos, P., Kallai, E., Liappas, I., Lea, R. W., & Kalofoutis, A. (2006). Indices of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population. Neuroscience Letters, 398(1–2), 118–123. https://doi.org/10.1016/j.neulet.2005.12.064
Dwita, L. P., Iwo, M. I., Elfahmi, & Mauludin, R. (2023a). Brain Antioxidant Properties of Piper cubeba L. Extracts and Essential Oil. Farmacia, 71(2), 296–302. https://doi.org/https://doi.org/10.31925/farmacia.2023.2.9
Dwita, L. P., Iwo, M. I., Mauludin, R., & Elfahmi. (2023b). Neuroprotective potential of lignan-rich fraction of Piper cubeba L. by improving antioxidant capacity in the rat’s brain. Brazilian Journal of Biology, 82, e266573. https://doi.org/10.1590/1519-6984.266573
Elfahmi, Ruslan, K., Batterman, S., Bos, R., Kayser, O., Woerdenbag, H. J., & Quax, W. J. (2007). Lignan profile of Piper cubeba, an Indonesian medicinal plant. Biochemical Systematics and Ecology, 35(7), 397–402. https://doi.org/10.1016/j.bse.2007.01.003
Godoy de Lima, R., Barros, M. T., & da Silva Laurentiz, R. (2018). Medicinal Attributes of Lignans Extracted from Piper Cubeba: Current Developments. ChemistryOpen, 7(2), 180–191. https://doi.org/10.1002/open.201700182
Hadwan, M. H. (2018). Simple spectrophotometric assay for measuring catalase activity in biological tissues. BMC Biochemistry, 19(1), 1–8. https://doi.org/10.1186/s12858-018-0097-5
Halliwell, B. (2006). Oxidative stress and neurodegeneration: Where are we now? Journal of Neurochemistry, 97(6), 1634–1658. https://doi.org/10.1111/j.1471-4159.2006.03907.x
Ibrahim, T., Kalam, M. A., Naqqash, N., Khan, S., Ashraf, B., Uvais, M., & Suhail, S. B. (2024). Kabābchīnī (Piper cubeba L.F.): A comprehensive review of its medicinal and therapeutic applications in Unani medicine. Journal of Medicinal Plants Studies, 12(4), 429–434. https://doi.org/10.22271/plants.2024.v12.i4e.1737
Jafarian, S., Ling, K., Hassan, Z., & Perimal-lewis, L. (2019). Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 5, 637–643. https://doi.org/10.1016/j.trci.2019.09.009
Kinda, P. T., Guenné, S., Basile, T., Ouédraogo, N., Compaoré, M., Bayala, B., Bild, W., Dobrin, R., Trus, C., Ciobică, A., & Kiendrebéogo, M. (2020). Brain protection and anti-amnesic effects assessment of Datura innoxia mill. Aqueous extracts. Farmacia, 68(2), 261–268. https://doi.org/10.31925/farmacia.2020.2.11
Klinkenberg, I., & Blokland, A. (2010). Neuroscience and Biobehavioral Reviews The validity of scopolamine as a pharmacological model for cognitive impairment : A review of animal behavioral studies. Neuroscience and Biobehavioral Reviews, 34(8), 1307–1350. https://doi.org/10.1016/j.neubiorev.2010.04.001
Lalkovičová, M., & Danielisová, V. (2016). Neuroprotection and antioxidants. Neural Regeneration Research, 11(6), 865–874. https://doi.org/10.4103/1673-5374.184447
Lee, K. H., Cha, M., & Lee, B. H. (2020). Neuroprotective Effect of Antioxidants in the Brain. International Journal of Molecular Science, 21(19), 7152. https://doi.org/doi:10.3390/ijms21197152
Ma, X., Zheng, C., Chen, Y., Pereira, F., & Li, Z. (2023). Working memory and reward increase the accuracy of animal location encoding in the medial prefrontal cortex. Cerebral Cortex, 33(5), 2245–2259. https://doi.org/10.1093/cercor/bhac205
Marcotullio, M. C., Pelosi, A., & Curini, M. (2014). Hinokinin, an emerging bioactive lignan. Molecules, 19(9), 14862–14878. https://doi.org/10.3390/molecules190914862
Mariani, E., Monastero, R., & Mecocci, P. (2007). Mild Cognitive Impairment: A Systematic Review. Journal of Alzheimer’s Disease, 12(1), 23–35. https://doi.org/10.3233/jad-2007-12104
Mothana, R. A., Al-Said, M. S., Raish, M., Khaled, J. M., Alharbi, N. S., Alatar, A., Ahmad, A., Al-Sohaibani, M., Al-Yahya, M., & Rafatullah, S. (2017). Chemical composition, anti-inflammatory and antioxidant activities of the essential oil of Piper cubeba L. Romanian Biotechnological Letters, 22, 2.
Pais, R., Ruano, L., Carvalho, O. P., & Barros, H. (2020). Global cognitive impairment prevalence and incidence in community dwelling older adults—a systematic review. Geriatrics, 5(4), 84. https://doi.org/10.3390/geriatrics5040084
Perazzo, F. F., Rodrigues, I. V., Maistro, E. L., Souza, S. M., Nanaykkara, N. P. D., Bastos, J. K., Carvalho, J. C. T., & De Souza, G. H. B. (2013). Anti-inflammatory and analgesic evaluation of hydroalcoholic extract and fractions from seeds of Piper cubeba L. (Piperaceae). Pharmacognosy Journal, 5(1), 13–16. https://doi.org/10.1016/j.phcgj.2012.12.001
Qomaladewi, N. P., Aziz, N., Kim, M.-Y. Y., & Cho, J. Y. (2019). Piper cubeba L. Methanol Extract Has Anti-Inflammatory Activity Targeting Src/Syk via NF-κB Inhibition. Evidence-Based Complementary and Alternative Medicine, 2019, 1548125. https://doi.org/10.1155/2019/1548125
Somani, G. S., Nahire, M. S., Parikh, A. D., Mulik, M. B., Ghumatkar, P. J., Laddha, K. S., & Sathaye, S. (2017). Neuroprotective effect of Cubebin: A dibenzylbutyrolactone lignan on scopolamine-induced amnesia in mice. The Indian Journal of Medical Research, 146(2), 255–259. https://doi.org/10.4103/ijmr.IJMR_156_14
Svensson, M., Hallin, T., Broms, J., Ekstrand, J., & Tingström, A. (2017). Spatial memory impairment in Morris water maze after electroconvulsive seizures. Acta Neuropsychiatrica, 29(1), 17–26. https://doi.org/10.1017/neu.2016.22
Sweatt, J. D. (2004). Hippocampal function in cognition. Psychopharmacology, 174(1), 99–110. https://doi.org/10.1007/s00213-004-1795-9
Tan, B. L., & Norhaizan, M. E. (2019). Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function. Nutrients, 11(11), 2579. https://doi.org/10.3390/nu11112579
Tarbiat, S., Unver, D., Tuncay, S., Isik, S., & Yeman, K. B. (2023). Neuroprotective e ff ects of Cubebin and Hinokinin lignan fractions of Piper cubeba fruit in Alzheimer’s disease in vitro model. Turkish Journal of Biochemistry, 48(3), 303–310. https://doi.org/10.1515/tjb-2023-0032
Veiga, V. F., Rosas, E. C., Carvalho, M. V., Henriques, M. G. M. O., & Pinto, A. C. (2007). Chemical composition and anti-inflammatory activity of copaiba oils from Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera multijuga Hayne—A comparative study. Journal of Ethnopharmacology, 112(2), 248–254. https://doi.org/10.1016/J.JEP.2007.03.005
Vorhees, C. V., & Williams, M. T. (2006). Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1(2), 848–858. https://doi.org/10.1038/nprot.2006.116
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Lusi Putri Dwita, Maria Immaculata Iwo, Elfahmi, Rachmat Mauludin
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The observations and associated materials published or posted by NeurosciRN are licensed by the authors for use and distribution in accord with the Creative Commons Attribution license CC BY-NC 4.0 international, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
