Sains Malaysiana 50(7)(2021): 2007-2015

http://doi.org/10.17576/jsm-2021-5007-15

Effects of Alpha-Mangostin Encapsulated in Nanostructured Lipid Carriers in Mice with Cerebral Ischemia Reperfusion Injury

(Kesan Alfa-Mangostin yang Dikapsulkan dalam Pembawa Lipid Berstruktur Nano pada Tikus dengan Kecederaan Reperfusi Iskemia Serebrum)

ROMGASE SAKAMULA¹, TEERAPONG YATA^2,3 & WACHIRYAH THONG-ASA¹*

¹Animal Toxicology and Physiology Specialty Research Unit (ATPSRU), Department of Zoology, Faculty of Science, Kasetsart University, Bangkok, Thailand

²National Nanotechnology Center (NANOTEC), Pathum Thani, Thailand

³Department of Physiology, Chulalongkorn University, Thailand

Received: 30 January 2020/Accepted: 11 November 2020

ABSTRACT

Cerebral ischemia reperfusion injury (CIRI) is a phenomenon in which the cerebral blood supply is restored after a period of ischemia, resulting in irreversible damage to brain tissue. Oxidative stress plays a crucial role in the development of CIRI, therefore, targeting oxidative stress might be an effective strategy for CIRI prevention and treatment. Many therapeutic substances possess antioxidant and protective properties against neurodegenerative disorders but lack of in vivo application due to their solubility, and bioavailability. We investigated the effects of alpha-mangostin (αM) encapsulated in nanostructured lipid carriers (αM-NLC) on CIRI in mice. Forty male ICR mice were randomly divided into four groups: Sham, ischemia reperfusion (IR), ischemia reperfusion with 25 mg/kg of αM (IR+αM), and ischemia reperfusion with 25 mg/kg of αM-NLC (IR+αM-NLC). After 6 days of oral administrations, IR was delivered using 30 min of bilateral common carotid artery occlusion, followed by 45 min of reperfusion. Cerebral infarction volume, hippocampal neuronal and corpus callosum (CC) white matter damage, malondialdehyde (MDA) level, and catalase (CAT) activity were evaluated. Our results indicated that αM and αM-NLC prevent lipid peroxidation as well as hippocampal CA1, CA3, and CC damage (p<0.05). Only αM-NLC prevented cerebral infarction and enhanced CAT activity (p<0.05). We therefore conclude that αM and αM-NLC have neuroprotective effects against CIRI, and NLC increases therapeutic efficacy of αM against CIRI.

Keywords: Alpha-mangostin; cerebral ischemia reperfusion injury; nanostructured lipid carrier; neurodegeneration; oxidative stress

ABSTRAK

Kecederaan reperfusi iskemia serebrum (CIRI) adalah fenomena bekalan darah serebrum dipulihkan setelah tempoh iskemia dan mengakibatkan kerosakan yang tidak dapat dipulihkan pada tisu otak. Tekanan oksidatif memainkan peranan penting dalam perkembangan CIRI, oleh itu, pensasaran tekanan oksidatif mungkin merupakan strategi yang berkesan bagi pencegahan dan rawatan CIRI. Banyak bahan terapeutik memiliki sifat antioksidan dan pelindung terhadap gangguan neurodegeneratif tetapi kekurangan aplikasiin vivo disebabkan keterlarutan dan ketersediaan bio. Kami mengkaji kesan alfa-mangostin (αM) yang dikapsulkan dalam pembawa lipid berstruktur nano (αM-NLC) pada CIRI atas tikus. Empat puluh tikus ICR jantan dibahagikan secara rawak kepada empat kumpulan: Sham, reperfusi iskemia (IR), reperfusi iskemia dengan 25 mg/kg αM (IR+αM) dan reperfusi iskemia dengan 25 mg/kg of αM-NLC (IR+αM-NLC). Selepas pemberian oral selama 6 hari, IR dihantar dengan menggunakan oklusi arteri karotid dua hala selama 30 min, diikuti dengan reperfusi selama 45 min. Isipadu infarksi serebrum, kerosakan bahan putih hipokampus neuron dan korpus kalosum (CC), tahap malondialdehid (MDA) dan aktiviti pemangkin (CAT) dinilai. Hasil kajian kami menunjukkan bahawa αM dan αM-NLC mencegah peroksidasi lipid serta kerosakan hipokampus CA1, CA3, dan CC (p<0.05). Hanya αM-NLC yang menghalang infraksi serebrum dan meningkatkan aktiviti pemangkin CAT (p<0.05). Oleh itu, kami menyimpulkan bahawa αM dan αM-NLC mempunyai kesan neuropelindung terhadap CIRI dan NLC meningkatkan keberkesanan terapeutik αM terhadap CIRI.

Kata kunci: Alfa-mangostin; kecederaan iskemia reperfusi serebrum; neurodegenerasi; pembawa lipid berstruktur nano; tekanan oksidatif

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*Corresponding author; email: fsciwyth@ku.ac.th