Ethanol Extracts of Ficus carica Fruit and Leaf Normalize High Serum Lipid Profile, TNF-α, and MDA due to High Fat Diet in Sprague Dawley Rat

Introduction

A diet called Western pattern diet (WPD) is characterized by a high intake of red meat, processed meat, pre-packed foods, butter, fried foods, potatoes, high-fructose corn syrup, and high-fat dairy products.¹ This dietary pattern is widespread in some Asian countries including Indonesia and it can result in dyslipidemia.² Dyslipidemia is characterized by abnormal levels of serum lipids with serum total cholesterol > 200 mg/dl, triglyceride > 150 mg/dl, LDL_chol > 160 mg/dl, HDL_chol < 40 mg/dl for males and < 50 mg/dl for females.³ Dyslipidemia is one of the main risk factors for cardiovascular disease (CVD) which is the major cause of death in the world.⁴ In 2016, 17.9 million people died from CVD, representing 31% of all global deaths.⁵

Dyslipidemia can lead to endothelial dysfunction where LDL_chol particles can easily enter into an arterial wall and trapped inside sub-intimal through apolipoprotein B100. Trapped LDL_chol particles can be damaged by free radicals and undergo oxidation.⁶ In addition, monocytes could penetrate arterial wall⁷ and release granulocyte and macrophages colony-stimulating factor (G-CSF dan M-CSF) in response to inflammation.⁶ Inflammation transforms monocyte into a macrophage.⁷ Macrophages combine lipoprotein such as beta-low density lipoprotein (βVLDL), acetylated low-density lipoprotein (AcLDL), and oxidized low-density lipoprotein (OxLDL) through a scavenger receptor (SR) on their surface.⁸ The combined lipoprotein is brought into liposomes to be hydrolized to free cholesterol and transported to endoplasmic reticulum to be re-esterified by acyl-CoA: cholesterol acyltransferase-1 (ACAT1). Esterified cholesterol is stored as a lipid-laden droplet causing macrophages to appear as foam and called foam cells.^8,9 Foam cells further produce proinflammatory cytokines such as interleukin (IL-1, IL-6), and Tumor Necrosis Factor-alpha (TNF-α). Increase proinflammatory cytokines can stimulate oxidative stress by increasing reactive oxygen species (ROS) which will attack polyunsaturated fatty acids (PUFAs) causing lipid peroxidation.^10,11 Lipid peroxidation produces lipid hydroperoxide which can be converted into malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), and some other forms of aldehydes.¹² Therefore, dyslipidemia induces production of proinflammatory cytokine TNF-α and biomarker of oxidative stress i.e. MDA.

Common fig (Ficus carica) plant, woody tree are cultivated for its edible fruit, and historically found in Northern Meditteranean countries such as Mecca, Syam, Palestine, and Egypt.