Sains Malaysiana 52(8)(2023): 2297-2308

http://doi.org/10.17576/jsm-2023-5208-10

The Effects of Abelmoschus esculentus (L.) Moench Seed on High Fat Diet Induced Metabolic and Cognitive Impairments in C57BL/6J Mice

(Kesan Biji Abelmoschus esculentus (L.) Moench pada Kemerosotan Metabolik dan Kognitif Terinduksi Diet Tinggi Lemak dalam Tikus C57BL/6J)

PAWEENA WONGWITWICHOT¹, SUPATTRA PROM-IN², JASADEE KAEWSRICHAN¹, NUNTIKA WANGPRADIT³, CHUA KIEN HUI⁴, MOHAMAD FAIRUZ YAHAYA⁵, AZIZAH UGUSMAN⁴ & JAYA KUMAR⁴

¹Department of Pharmaceutical Chemistry and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand

²Department of Thai Traditional Medicine, Faculty of Health and Sport Sciences, Thaksin University, 93210, Thailand

³International College of Dentistry and Biomass and Oil Palm Center of Excellence, Walailak University, Nakhon Si Thammarat 80160, Thailand

⁴Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia

⁵Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia

Diserahkan: 14 Februari 2023/Diterima: 26 Julai 2023

Abstract

Okra is known for its neuroprotective and antioxidant properties. We aimed to investigate the potential effects of okra seed powder in alleviating high far diet (HFD) induced cognitive deficit and hypercholesterolemia.  We randomly allocated thirty-six C57BL/6J male mice into: (i) control, mice fed with a normal fat level diet; (ii) HFD, mice fed with HFD; (iii) HFD-OS1; (iv) HFD-OS2; (v) HFD-OS3, mice fed with HFD and okra seed powder (200, 400, or 800 mg/kg/day, respectively); (vi) HFD-SIM, mice fed with HFD and simvastatin (20 mg/kg/day). After 10 weeks of treatment period, the mice were tested with an episodic-like memory test (EMT) and Morris water maze (MWM). We found significantly higher total and LDL cholesterol levels in mice fed with HFD. Compared to the HFD group, the control group performed better in the EMT test, and also learned and retrieved spatial reference memory better in the MWM test.  The okra seed powder significantly improved spatial learning in four days of acquisition trials and the highest dose of okra profoundly improved spatial reference memory retention during the probe trial. Contrary to the MWM results, the okra-treated animals did not perform significantly better than the HFD-treated animals in EMT. At present, we recommend future studies testing the potential neuroprotective or cognitive enhancing effects of okra to assess different cognitive domains using various disease models to have a better understanding on the potential neuroprotective properties of okra.

Keywords: Abelmoschus esculentus (L.) Moench (okra); cognitive impairment; high-fat diet

Abstrak

Okra terkenal dengan kesan antioksidan dan neuropelindungnya. Kajian ini bertujuan untuk menilai sama ada serbuk biji bendi mampu mengurangkan kerosakan kognitif dan hiperkolesterolemia akibat HFD. Kami secara rawak membahagikan tiga puluh enam mencit jantan C57BL/6J kepada: (i) kawalan, mencit yang diberi makan dengan diet yang mengandungi tahap lemak normal; (ii) HFD, mencit diberi makan dengan HFD; (iii) HFD-SIM, mencit diberi makan dengan HFD dan diberikan simvastatin (20 mg/kg/hari); (iv) HFD-OS1; (v) HFD-OS2; (vi) HFD-OS3, mencit yang diberi HFD dan serbuk biji bendi (masing-masing 200, 400, atau 800 mg/kg/hari). Setelah 10 minggu rawatan, mencit telah didedahkan kepada ujian ingatan seperti episodik (EMT) dan Morris Water Maze (MWM). Mencit yang diberi makan dengan HFD mencatatkan jumlah dan tahap kolesterol LDL yang jauh lebih tinggi. Untuk EMT, haiwan kawalan berprestasi lebih baik daripada kumpulan HFD. Dalam ujian MWM, haiwan kawalan belajar dan mendapatkan semula ingatan rujukan reruang dengan lebih ketara berbanding kumpulan HFD. Serbuk biji bendi tidak menghasilkan sebarang kesan ketara dalam EMT, walau bagaimanapun, pembelajaran reruang bertambah baik dengan ketara dalam empat hari percubaan pemerolehan dan dos tertinggi bendi meningkatkan pengekalan memori rujukan reruang dengan ketara semasa Probe Trial. Walaupun dengan ketara meningkatkan pembelajaran reruang dan pengekalan ingatan dalam MWM, tiada haiwan yang dirawat okra menunjukkan prestasi yang lebih baik daripada kumpulan HFD dalam EMT. Oleh itu, kami mengesyorkan kajian masa depan yang berkaitan dengan okra untuk menguji komponen kognitif yang berbeza untuk mempunyai pemahaman yang jelas tentang kesan neuropelindung okra.

Kata kunci: Abelmoschus esculentus (L.) Moench (okra); diet tinggi lemak; kemerosotan kognitif

RUJUKAN

Adila A. Hamid, Amilia Aminuddin, Mohd Heikal Mohd Yunus, Jaya Kumar Murthy, Chua Kien Hui & Azizah Ugusman. 2020. Antioxidative and anti-inflammatory activities of Polygonum minus: A review of literature. Reviews in Cardiovascular Medicine 21(2): 275-287.

Amilia Aminuddin, Md Rizman MLM Lazim, Adila A. Hamid, Chua K. Hui, Mohd H. Mohd Yunus, Jaya Kumar & Azizah Ugusman. 2020. The association between inflammation and pulse wave velocity in dyslipidemia: An evidence-based review. Mediators of Inflammation 2020: 4732987.

Arapitsas, P. 2008. Identification and quantification of polyphenolic compounds from okra seeds and skins. Food Chemistry 110(4): 1041-1045.

Bhat, N.R. & Thirumangalakudi, L. 2013. Increased tau phosphorylation and impaired brain insulin/IGF signaling in mice fed a high fat/high cholesterol diet. Journal of Alzheimer's Disease 36(4): 781-789.

Bromley-Brits, K., Deng, Y. & Song, W. 2011. Morris water maze test for learning and memory deficits in Alzheimer's disease model mice. Journal of Visualized Experiments 53: e2920.

Cahyana, A.H. & Kam, N. 2016. Study on the stability of antioxidant and anti α-glucosidase activities using soaking treatment in okra (Abelmoschus esculentus L.) mucilage extraction. Chemistry International 3(3): 202-211.

Carey, A.N., Gomes, S.M. & Shukitt-Hale, B. 2014. Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet. Journal of Agricultural and Food Chemistry 62(18): 3972-3978.

Cavaliere, G., Trinchese, G., Penna, E., Cimmino, F., Pirozzi, C., Lama, A., Annunziata, C., Catapano, A., Mattace Raso, G., Meli, R., Monda, M., Messina, G., Zammit, C., Crispino, M. & Mollica, M.P. 2019. High-fat diet induces neuroinflammation and mitochondrial impairment in mice cerebral cortex and synaptic fraction. Frontiers in Cellular Neuroscience 13: 509.

Cheke, L.G., Bonnici, H.M., Clayton, N.S. & Simons, J.S. 2017. Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain. Neuropsychologia 96: 137-149.

Chua Ken Hui, Isa Naina Mohamed, Mohd Heikal Mohd Yunus, Norefrina Shafinaz Md Nor, Khidhir Kamil, Azizah Ugusman & Jaya Kumar. 2021. The anti-viral and anti-inflammatory properties of Edible Bird’s nest in influenza and coronavirus infections: From pre-clinical to potential clinical Application. Frontiers in Pharmacology 12: 633292.

Cordner, Z.A. & Tamashiro, K.L.K. 2015. Effects of high-fat diet exposure on learning & memory. Physiology & Behavior 152: 363-371.

de Alvarenga Pinto Cotrim, M., Caron Mottin, A. & Ayres, E. 2016. Preparation and characterization of okra mucilage (Abelmoschus esculentus) edible films. Macromolecular Symposia 367(1) (Special Issue: Brazilian Polymer Conference Part 1): 90-100.

Dere, E., Huston, J.P. & De Souza Silva, M.A. 2005a. Integrated memory for objects, places, and temporal order: Evidence for episodic-like memory in mice. Neurobiology of Learning and Memory 84(3): 214-221.

Dere, E., Huston, J.P. & De Souza Silva, M.A. 2005b. Episodic-like memory in mice: Simultaneous assessment of object, place and temporal order memory. Brain Research Protocols 16(1-3): 10-19.

Dubey, P. & Mishra, S. 2017. Effect of okra seed in reduction of cholesterol. Journal of Entomology and Zoology Studies 5(4): 94-97.

Gardener, S.L., Rainey-Smith, S.R., Barnes, M.B., Sohrabi, H.R., Weinborn, M., Lim, Y.Y., Harrington, K., Taddei, K., Gu, Y., Rembach, A., Szoeke, C., Ellis, K.A., Masters, C.L., Macaulay, S.L., Rowe, C.C., Ames, D., Keogh, J.B., Scarmeas, N. & Martins, R.N.    for the AIBL Research Group. 2015. Dietary patterns and cognitive decline in an Australian study of ageing. Molecular Psychiatry 20(7): 860-866.

Heyward, F.D., Walton, R.G., Carle, M.S., Coleman, M.A., Garvey, W.T. & Sweatt, J.D. 2012. Adult mice maintained on a high-fat diet exhibit object location memory deficits and reduced hippocampal SIRT1 gene expression. Neurobiology of Learning and Memory 98(1): 25-32.

Huang, P.L. 2009. A comprehensive definition for metabolic syndrome. Disease Models & Mechanisms 2(5-6): 231-237.

Kaewsrichan, J., Wongwitwichot, P. & Manee, S. 2020. Health effects of ethanolic extract from seeds of lady finger. Food and Health 6(2): 90-97.

Kahlon, T.S., Chapman, M.H. & Smith, G.E. 2007. In vitro binding of bile acids by okra, beets, asparagus, eggplant, turnips, green beans, carrots, and cauliflower. Food Chemistry 103(2): 676-680.

Kamal Haziq, Khidhir Kamil, T. Nelson, Abdul Latif Noor, Manmeet Kaur Amiruddin, Prithviraj Singh, Aina Nurul, Nursyahirah Johaniff, Abdul Halim & Azmawati Mohammed. 2021. Effects of traditional and convenient edible bird’s nest on spatial learning of male Sprague-Dawley rats. Sains Malaysiana 50(12): 3537-3545.

Kamal Haziq, Geok Chin Tan, Siti Fatimah Ibrahim, Mohd Farooq Shaikh, Isa Naina Mohamed, Rashidi M. Pakri Mohamed, Adila A. Hamid, Azizah Ugusman & Jaya Kumar. 2020. Alcohol use disorder, neurodegeneration, Alzheimer’s and Parkinson’s disease: Interplay between oxidative stress, neuroimmune response and excitotoxicity. Frontiers in Cellular Neuroscience 14: 282.

Kang, J., Wang, Z. & Oteiza, P.I. 2020. (−)-Epicatechin mitigates high fat diet-induced neuroinflammation and altered behavior in mice. Food & Function 11(6): 5065-5076.

Khidhir Kamil, Muhammad Dain Yazid, Ruszymah Bt Hj Idrus & Jaya Kumar. 2020. Hydroxytyrosol promotes proliferation of human schwann cells: An in vitro study. International Journal of Environmental Research and Public Health 17(12): 4404.

Khidhir Kamil, Jaya Kumar, Muhammad Dain Yazid & Ruszymah Binti Haji Idrus. 2018. Olive and its phenolic compound as the promising neuroprotective agent. Sains Malaysiana 47(11): 2811-2820.

Kim, D.H. & Ryu, J.H. 2008. Differential effects of scopolamine on memory processes in the object recognition test and the Morris water maze test in mice. Biomolecules & Therapeutics 16(3): 173-178.

Kita, T., Brown, M.S. & Goldstein, J.L. 1980. Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of mice treated with mevinolin, a competitive inhibitor of the reductase. The Journal of Clinical Investigation 66(5): 1094-1100.

Kothari, V., Luo, Y., Tornabene, T., O'Neill, A.M., Greene, M.W., Thangiah, G. & Jeganathan, R.B. 2017. High fat diet induces brain insulin resistance and cognitive impairment in mice. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1863(2): 499-508.

Kumar Jaya, Seong Lin Teoh, Srijit Das & Pasuk Mahakknaukrauh. 2017. Oxidative stress in oral diseases: Understanding its relation with other systemic diseases. Frontiers in Physiology 8: 693.

Manee, S. & Kaewsrichan, J. 2017. Cosmeceutical benefit of Abelmoschus esculentus L. seed extract. J. Pharm. Res. Int. 19(6): 1-11.

Martínez-Orozco, H., Reyes-Castro, L.A., Lomas-Soria, C., Sandoval-Salazar, C., Ramírez-Emiliano, J., Díaz-Cintra, S. & Solís-Ortiz, S. 2022. High-fat and combined high-fat-high-fructose diets impair episodic-like memory and decrease glutamate and glutamine in the hippocampus of adult mice. Nutritional Neuroscience 25(12): 2479-2489.

McLean, F.H., Grant, C., Morris, A.C., Horgan, G.W., Polanski, A.J., Allan, K., Campbell, F.M., Langston, R.F. & Williams, L.M. 2018. Rapid and reversible impairment of episodic memory by a high-fat diet in mice. Scientific Reports 8(1): 1-9.

Ngoc, T.H., Ngoc, Q.N., T Van, A.T. & Phung, N.V. 2008. Hypolipidemic effect of extracts from Abelmoschus esculentus L. (Malvaceae) on tyloxapol-induced hyperlipidemia in mice. Pharmaceutical Sciences Asia (Formerly Mahidol University Journal Pharmaceutical Sciences) 35(1-4): 42-46.

Nurul ‘Ain Arshad, Teoh Seong Lin & Mohamad Fairuz Yahaya. 2018. Metabolic syndrome and its effect on the brain: Possible mechanism. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders) 17(8): 595-603.

Ouweneel, A.B., van der Sluis, R.J., Nahon, J.E., Van Eck, M. & Hoekstra. M. 2017. Simvastatin treatment aggravates the glucocorticoid insufficiency associated with hypocholesterolemia in mice. Atherosclerosis 261: 99-104.

Park, H.R., Park, M., Choi, J., Park, K-Y., Chung, H.Y. & Lee, J. 2010. A high-fat diet impairs neurogenesis: Involvement of lipid peroxidation and brain-derived neurotrophic factor. Neuroscience Letters 482(3): 235-239.

Prom-In, S., Kaewsrichan, J., Wangpradit, N., Chua Kien Hui, Mohamad Fairuz Yahaya, Yusof Kamisah & Jaya Kumar. 2020. Abelmoschus esculentus (L.) Moench’s peel powder improves high-fat-diet-induced cognitive impairment in C57BL/6J mice. International Journal of Environmental Research and Public Health 17(15): 5513.

Robison, L.S., Albert, N.M., Camargo, L.A., Anderson, B.M., Salinero, A.E., Riccio, D.A., Abi-Ghanem, C., Gannon, O.J. & Zuloaga, K.L. 2020. High-fat diet-induced obesity causes sex-specific deficits in adult hippocampal neurogenesis in mice. Eneuro 7(1):ENEURO.0391-19.2019.

Roy, A., Shrivastava, S.L. & Mandal, S.M. 2014. Functional properties of okra Abelmoschus esculentus L. (Moench): Traditional claims and scientific evidences. Plant Science Today 1(3): 121-130.

Saiyasit, N., Chunchai, T., Apaijai, N., Pratchayasakul, W., Sripetchwandee, J., Chattipakorn, N. & Chattipakorn, S.C. 2020. Chronic high-fat diet consumption induces an alteration in plasma/brain neurotensin signaling, metabolic disturbance, systemic inflammation/oxidative stress, brain apoptosis, and dendritic spine loss. Neuropeptides 82: 102047.

Sharma, S., Rakoczy, S. & Brown-Borg, H. 2010. Assessment of spatial memory in mice. Life Sciences 87(17-18): 521-536.

Shefer, G., Marcus, Y. & Stern, N. 2013. Is obesity a brain disease? Neuroscience & Biobehavioral Reviews 37(10): 2489-2503.

Sparrow, C.P., Burton, C.A., Hernandez, M., Mundt, S., Hassing, H., Patel, S., Rosa, R., Hermanowski-Vosatka, A., Wang, P.R., Zhang, D., Peterson, L., Detmers, P.A., Chao, Y.S. & Wright, S.D. 2001. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arteriosclerosis, Thrombosis, and Vascular Biology 21(1): 115-121.

Tongjaroenbuangam, W., Ruksee, N., Chantiratikul, P., Pakdeenarong, N., Kongbuntad, W. & Govitrapong, P. 2011. Neuroprotective effects of quercetin, rutin and okra (Abelmoschus esculentus Linn.) in dexamethasone-treated mice. Neurochemistry International 59(5): 677-685.

Vijayakumar, S., Ramachandran, S., Naveen, K. & Panneerselvam, K. 2012. Investigation of in vivo antioxidant property of Abelmoschus esculentus (L) Moench. fruit seed and peel powders in streptozotocin-induced diabetic rats. Journal of Ayurveda and Integrative Medicine 3(4): 188.

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.

World Health Organization (WHO). 2018.  Obesity and overweight. http://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight

Yan, T., Nian, T., Wu, B., Xiao, F., He, B., Bi, K. & Jia, Y. 2020. Okra polysaccharides can reverse the metabolic disorder induced by high-fat diet and cognitive function injury in Aβ1-42 mice. Experimental Gerontology 130: 110802.

You, S.H., Jang, M. & Kim, G-H. 2020. Mori Cortex radicis attenuates high fat diet-induced cognitive impairment via an IRS/Akt signaling pathway. Nutrients 12(6): 1851.

*Pengarang untuk surat-menyurat; email: jayakumar@ukm.edu.my