Sains Malaysiana 51(3)(2022): 803-814

http://doi.org/10.17576/jsm-2022-5103-14

The Effects of Clitoria ternatea Extract on Zebrafish Model of Alzheimer’s Disease: A Neurobehavioural Study

(Kesan Ekstrak Clitoria ternatea pada Model Ikan Zebra bagi Penyakit Alzheimer: Suatu Kajian Tingkah Laku Neuron)

MUHAMMAD DANIAL BIN CHE RAMLI^1,*, NUR ARISSA SYAZWANI BINTI MD NAZREY¹, MAHATHIR BIN MOHD UZID¹, ANITA ZARA WEINHEIMER¹, NUR BATRISYIA BINTI NIZAM¹, NADHRATUN NABILA BINTI MAZLAN¹, NURSHAFIQAH NAJIHAH BINTI MOHD MIZAN¹, HUSSIN MUHAMMAD², MOHAMAD ANUAR AHAD³ & MOHAMAD AZMEER EFFENDY³

¹Faculty of Health and Life Sciences, Management and Science University, 40100 Shah Alam, Selangor Darul Ehsan, Malaysia

²Toxicology & Pharmacology Unit, Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Jalan Setia Murni U13/52, Seksyen U13 Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia

³Center for Drug Research, Universiti Sains Malaysia, 11800 Gelugor, Penang, Malaysia

Diserahkan: 30 Disember 2020/Diterima: 26 Julai 2021

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is currently affecting 40-50 million people worldwide. It is generally recognized from its main symptom dementia, in which the patient undergoes a progressive decline in their cognitive memory. Recent studies have shown that medicinal plants such as Clitoria ternatea equipped with antioxidant properties has high potential in treating AD. The study was conducted using zebrafish model of AD induced with aluminium chloride for 28 days. The treatment dose of C. ternatea extract (4.34 mg/L) was then given for 14 days. The behaviour of the zebrafish were evaluated through memory testing by using a T-maze test and novel tank diving test. Histological studies were also performed. 50% of the zebrafish tested showed improvement in memory through the T-maze test after treatment with C. ternatea extract. Zebrafish model of AD treated with C. ternatea extract also shows a decrease in anxiety in the novel tank diving test. A significant increase of purkinje cells were also observed from the histological study after treatment with C. ternatea extract. Nucleus elongation of oligodendrocytes from zebrafish model of AD induced with aluminium chloride were improved when treated with the C. ternatea extract. In conclusion, it was found that C. ternatea extract exhibits strong potential for treating zebrafish model of AD induced with aluminium chloride.

Keyword: Alternative treatment; Alzheimer’s disease; Clitoria ternatea; neurodegenerative; Zebrafish model

Abstrak

Penyakit Alzheimer adalah penyakit kemerosotan neuron yang kini menjejaskan 40-50 juta orang di seluruh dunia. Ia secara amnya dikenali melalui gejala utamanya iaitu demensia, apabila pesakit mengalami kemerosotan dalam ingatan kognitif mereka. Kajian baru-baru ini telah menunjukkan bahawa tumbuhan perubatan seperti Clitoria ternatea yang dilengkapi dengan sifat antioksidan mempunyai potensi yang tinggi dalam merawat penyakit Alzheimer. Penyelidikan ini dijalankan dengan menggunakan model ikan Zebra yang telah diberikan penyakit Alzheimer menggunakan aluminium klorida selama 28 hari. Dos rawatan menggunakan tumbuhan C. ternatea sebanyak 4.34 mg/L kemudiannya diberikan selama 14 hari. Tingkah laku ikan Zebra telah dinilai melalui ujian ingatan dengan menggunakan ujian pagar sesat dan ujian penyelaman tangki. Kajian histologi juga telah dilakukan. 50% daripada ikan Zebra yang diuji menunjukkan peningkatan dalam ingatan melalui ujian pagar sesat selepas rawatan dengan ekstrak C. ternatea. Ikan Zebra yang dirawat dengan ekstrak C. ternatea juga menunjukkan penurunan tahap kegelisahan dalam ujian penyelaman tangki. Peningkatan bilangan sel purkinje juga dapat diperhatikan daripada kajian histologi selepas dirawat dengan ekstrak C. ternatea. Pemanjangan nukleus ‘oligodendrocytes’ di dalam sel otak ikan Zebra yang dijangkiti penyakit Alzheimer telah bertambah baik apabila dirawat dengan ekstrak C. ternatea. Kesimpulannya, kajian ini telah mendapati bahawa ekstrak C. ternatea menunjukkan potensi yang tinggi untuk merawat ikan Zebra yang telah dijangkiti dengan penyakit Alzheimer.

Kata kunci: Clitoria ternatea; kemerosotan neuron; model ikan Zebra; Penyakit Alzheimer; rawatan alternative

RUJUKAN

Ali, M.K., Saber, S.P., Taite, D.R., Emadi, S. & Irving, R. 2017. The protective layer of zebrafish embryo changes continuously with advancing age of embryo development (AGED). J. Toxicol. Pharmacol. 1(2): 9.

Avdesh, A., Martin-Iverson, M.T., Mondal, A., Chen, M., Askraba, S., Morgan, N., Lardelli, M., Groth, D.M., Verdile, G. & Martins, R.N. 2012. Evaluation of color preference in zebrafish for learning and memory. Journal of Alzheimer's Disease 28(2): 459-469.

Birks, J.S. & Harvey, R.J. 2018. Donepezil for dementia due to Alzheimer's disease. Cochrane Database of Systematic Reviews 6(6): CD001190.

Birks, J.S. & Evans, J.G. 2015. Rivastigmine for Alzheimer's disease. Cochrane Database of Systematic Reviews 10(4): CD001191.

Butt, A.M., De La Rocha, I.C. & Rivera, A. 2019. Oligodendroglial cells in Alzheimer’s disease. Neuroglia in Neurodegenerative Diseases 1175: 325-333.

Caramillo, E.M. & Echevarria, D.J. 2017. Alzheimer’s disease in the zebrafish: Where can we take it? Behavioural Pharmacology 28(2): 179-186.

De Strooper, B. & Karran, E. 2016. The cellular phase of Alzheimer’s disease. Cell 164(4): 603-615.

Durga Mahalakshmi, CH. N., D. Prathyusha, T. Madhavi, G. Swathi & N. John Sushma. 2015. Antioxidant role of Clitoria ternatea extract against aluminum-induced oxidative stress in hippocampus of albino rats. Int. J. Sci. Eng. Res. 6(2): 156-160.

Egan, R.J., Bergner, C.L., Hart, P.C., Cachat, J.M., Canavello, P.R., Elegante, M.F., Elkhayat S.I., Bartels, B.K., Tien, A.K., Tien, D.H., Mahnot, S., Beeson, E., Glasgow, E., Amri, H., Zukowska, Z. & Kalueff, A.V. 2009. Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish. Behavioural Brain Research 205(1): 38-44.

Fan, W-J., Yan, M-C., Wang, L., Sun, Y-Z., Deng, J-B. & Deng, J-X. 2018. Synaptic aging disrupts synaptic morphology and function in cerebellar Purkinje cells. Neural Regeneration Research 13(6): 1019-1025.

Halim Shukri Kamaruddin & Noriszura Ismail. 2019. Statistical comparison of projection Malaysia mortality rate by using Lee-Carter model and Lee-Carter extension of Hyndman-Ullah. In AIP Conference Proceedings 2111(1): 020007.

Hemamalini, S. & Rao, M.S. 2018. Neuroprotective efficacy of Clitoria ternacea root extract on hippocampal CA3 neurons - A quantitative study in mice. Journal of Morphological Sciences 35(2): 90-95.

Huang, W., Li, C., Shen, Z., Zhu, X., Xia, B. & Li, C. 2016. Development of a zebrafish model for rapid drug screening against Alzheimer’s disease. Journal of Pharmacy and Pharmacology 4: 174-185.

Jain, N.N., Ohal, C.C., Shroff, S.K., Bhutada, R.H., Somani, R.S., Kasture, V.S. & Kasture, S.B. 2003. Clitoria ternatea and the CNS. Pharmacology Biochemistry and Behavior 75(3): 529-536.

Kamilla, L., Ramanathan, S., Sasidharan, S. & Mansor, S.M. 2012. Toxicity evaluation of methanol extract of Clitoria ternatea L. leaf. Malaysian Journal of Medicine and Health Sciences 8(2): 33-39.

Kim, Y-H., Lee, K.S., Park, A.R. & Min, T.J. 2017. Adding preferred color to a conventional reward method improves the memory of zebrafish in the T-maze behavior model. Animal Cells and Systems 21(6): 374-381.

Kumar, S. 1998. Biphasic effect of aluminium on cholinergic enzyme of rat brain. Neuroscience Letters 248(2): 121-123.

Md Bakhtiar Lijon, Nigar Sultana Meghla, E. Jahedi, Md A. Rahman & Ismail Hossain. 2017. Phytochemistry and pharmacological activities of Clitoria ternatea. International Journal of Natural and Social Sciences 4(1): 1-10.

Muhammad Danial Bin Che Ramli, Wan Nadiah Chong Binti Muhammad Ridzuan Chong, Mahathir Bin Mohd Uzid & Junedah Sanusi. 2019. The neurotoxicity assessment in addicted adult zebrafish (Danio rerio) induced by mitragyna speciosa. International Journal of Medical Toxicology & Legal Medicine 22(3 & 4): 63-68.

Nunes, M.E., Müller, T.E., Braga, M.M., Fontana, B.D., Quadros, V.A., Marins, A., Rodrigues, C., Menezes, C., Rosemberg, D.B. & Loro, V.L. 2017. Chronic treatment with paraquat induces brain injury, changes in antioxidant defenses system, and modulates behavioral functions in zebrafish. Molecular Neurobiology 54(6): 3925-3934.

Padmaja, R., Arun, P.C., Prashanth, D., Deepak, M., Amit, A. & Anjana, M. 2002. Brine shrimp lethality bioassay of selected Indian medicinal plants. Fitoterapia 73(6): 508-510.

Pilehvar, A., Town, R.M. & Blust, R. 2020. The effect of copper on behaviour, memory, and associative learning ability of zebrafish (Danio rerio). Ecotoxicology and Environmental Safety 188: 109900.

Rai, K.S., Murthy, K.D., Karanth, K.S., Nalini, K., Rao, M.S. & Srinivasan, K.K. 2002. Clitoria ternatea root extract enhances acetylcholine content in rat hippocampus. Fitoterapia 73(7-8): 685-689.

Ruchi Jakhmola Mani, Khyati Mittal & Deepshikha Pande Katare. 2018. Protective effects of quercetin in zebrafish model of Alzheimer’s disease. Asian Journal of Pharmaceutics 12(2): S660.

Samaila Musa Chiroma, Mohamad Taufik Hidayat Baharuldin, Che Norma Mat Taib, Zulkhairi Amom, Saravanan Jagadeesan, Mohd Ilham Adenan & Mohamad Aris Mohd Moklas. 2019. Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches. Biomedicine & Pharmacotherapy 109: 853-864.

Sandra Vranic, Yasuhito Shimada, Sahoko Ichihara, Masayuki Kimata, Wenting Wu, Toshio Tanaka, Sonja Boland, Lang Tran & Gaku Ichihara. 2019. Toxicological evaluation of SiO₂ nanoparticles by zebrafish embryo toxicity test. International Journal of Molecular Sciences 20(4): 882.

Senger, M.R., Seibt, K.J., Ghisleni, G.C., Dias, R.D., Bogo, M.R. & Bonan, C.D. 2011. Aluminum exposure alters behavioral parameters and increases acetylcholinesterase activity in zebrafish (Danio rerio) brain. Cell Biology and Toxicology 27(3): 199-205.

Strungaru, S.A., Radojković, P., Dumitru, G., Nicoara, M.N., Plavan, G.I. & Todirascu-Ciornea, E. 2019. Oxidative stress and changes in swimming performances at zebrafish model (Danio rerio H. 1822) produced by acute exposure to deltamethrin. Survey in Fisheries Sciences 5(2): 121-137.

Taranalli, A.D. & Cheeramkuzhy, T.C. 2000. Influence of Clitoria ternatea extracts on memory and central cholinergic activity in rats. Pharmaceutical Biology 38(1): 51-56.

Tayebeh Enayat Gholampour, Raha Fadaei Raieni, Mojtaba Pouladi, Mohamad Larijani, Maria Pagano & Caterina Faggio. 2020. The dietary effect of Vitex agnus-castus hydroalcoholic extract on growth performance, blood biochemical parameters, carcass quality, sex ratio and gonad histology in Zebrafish (Danio rerio). Applied Sciences 10(4): 1402.

Thangal Yumnamcha, Debasish Roy, M. Damayanti Devi & Upendra Nongthomba. 2015. Evaluation of developmental toxicity and apoptotic induction of the aqueous extract of Millettia pachycarpa using zebrafish as model organism. Toxicological & Environmental Chemistry 97(10): 1363-1381.

Wu, Y-T., Beiser, A.S., Breteler, M.M.B., Fratiglioni, L., Helmer, C., Hendrie, H.C., Honda, H., Ikram, M.A., Langa, K.M., Lobo, A., Matthews, F.E., Ohara, T., Péres, K., Qiu, C., Seshadri, S., Sjölund, B-M., Skoog, I. & Brayne, C. 2017. The changing prevalence and incidence of dementia over time - current evidence. Nature Reviews Neurology 13(6): 327-339.

^*Pengarang untuk surat-menyurat; email: muhammaddanialramli@gmail.com