Sains Malaysiana 49(5)(2020): 1055-1066

http://dx.doi.org/10.17576/jsm-2020-4905-10

  Alterations of Cholesterol Lowering-Related Proteins in the Serum of Hypercholesterolemic-Induced Rats Treated with Ficus deltoidea

(Pengubahan Kolesterol Protein Berkaitan Penurunan dalam Serum Tikus Teraruh Hiperkolesterolimia Dirawat dengan Ficus deltoidea)

CHUO PECK HAM¹, FATIMA UZAR¹, PUTERI SHAFINAZ ABDUL-RAHMAN^2,3, NOORLIDAH ABDULLAH¹ & NORHANIZA AMINUDIN^1,3*

¹Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

²Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

³University of Malaya Centre for Proteomics Research (UMCPR), University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

Received: 2 September 2019/Accepted: 28 January 2020

ABSTRACT

Cardiovascular disease (CVD) is one of the major non-communicable diseases causing cardiac dysfunction and heart failure. In Malaysia, hypercholesterolemia or high blood cholesterol is known as CVD’s main risk factor. Currently, there is a paradigm shift of interest in Eastern medicines as alternative prevention approaches and therapeutic cholesterol control treatment. Ficus deltoidea (Mas Cotek) is amongst the eastern medicinal plants traditionally consumed either as prevention or treatment for various diseases such as hypertension, diabetes and hypercholesterolemia. This study utilised the proteomic application in determining the changes in a series of proteins that are being differentially expressed in response to F. deltoidea treatment of hypercholesterolemic-induced rats. Identification and quantification of proteins were conducted by using quantitative techniques, wherein two dimensional gel electrophoresis (2D-GE) along with Progenesis Samespots image analysis software and Matrix-assisted laser desorption/ionization Time-of-flight/Time-of-flight (MALDI ToF/ToF) mass spectrometry were utilised. Our results demonstrated that 14 protein spots had displayed alteration in their abundance at a minimum of 1.5 fold. Majority of these identified proteins were involved in lipid metabolism and immune system processes. These variables include apolipoprotein A1 (Apo A1), apolipoprotein E (Apo E), retinol binding protein 4 (RBP4), haptoglobin (HP), complement factor C3 (C3), complement factor C1s (C1s), transthyretin (TTR), ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3), prominin 1(PROM1) and plasminogen (PLG). Serum proteome analysis has unravelled the understanding on the mechanism of cholesterol reducing by F. deltoidea via augmentation of cholesterol biosynthesis that enhanced bile acids excretion, causing lowered cholesterol absorption in hypercholesterolemic rats.

Keywords: 2D-GE; differential expressions; Ficus deltoidea; hypercholesterolemia; MALDI ToF/ToF MS

ABSTRAK

Penyakit kardiovaskular (CVD) adalah sejenis penyakit tidak berjangkit paling utama yang menyebabkan disfungsi kardiak dan kegagalan fungsi jantung. Di Malaysia, hiperkolesterolemia atau kandungan kolesterol yang tinggi di dalam darah merupakan faktor risiko umum penyakit kardiovaskular. Kini, perubatan alternatif timur semakin diterima sebagai rawatan pencegahan dan terapeutik untuk mengawal paras kolesterol darah. Ficus deltoidea (Mas Cotek) adalah antara tumbuhan yang digunakan di dalam perubatan tradisi timur bagi tujuan pencegahan atau rawatan penyakit tekanan darah tinggi, kencing manis dan kolesterol darah tinggi. Kajian ini menggunakan aplikasi kaedah proteomik untuk mengenal pasti protein yang menunjukkan perubahan ketara berikutan rawatan F. deltoidea ke atas tikus hiperkolesterolemik. Pengenalpastian dan pengkuantitian protein telah dijalankan dengan menggunakan teknik kuantitatif relatif seperti 2D-GE dengan bantuan perisian analisis imej Progenesis Samespots dan analisis spektrometer jisim MALDI ToF/ToF. Kajian kami menunjukkan terdapat 14 titik protein yang menunjukkan perubahan ketara dengan sekurang-kurangnya 1.5 kali ganda. Kebanyakan protein yang dikenal pasti  terlibat dalam metabolisma dan pengangkutan lipid serta tindak balas radang dan imun. Ini termasuklah apolipoprotein A1 (Apo A1), apolipoprotein E (Apo E), retinol binding protein 4 (RBP4), haptoglobin (HP), complement factor C3 (C3), complement factor C1s (C1s), transthyretin (TTR), ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3), prominin 1(PROM1) dan plasminogen (PLG). Penemuan protein-protein ini memberikan maklumat baru dalam pemahaman tindak balas molekul terhadap mekanisme yang terlibat dalam penurunan kolesterol berikutan rawatan F. deltoidea melalui biosintesis kolesterol yang meningkatkan penguraian asid hempedu sekaligus menurunkan penyerapan kolesterol di dalam tikus hiperkolesterolemik.

Kata kunci: 2D-GE; Ficus deltoidea; hiperkolesterolemia; perbezaan tahap pengekspresan; spektrometer jisim MALDI ToF/ToF

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*Corresponding author; email: hanizaaminudin@um.edu.my