Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E-NTPDase in acute hyperlipidemia |
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| Authors: | Reem S. Alruhaimi Maisa Siddiq Abduh Ahmad F. Ahmeda Albandari Bin-Ammar Emadeldin M. Kamel Emad H. M. Hassanein Chen Li Ayman M. Mahmoud |
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| Affiliation: | 1. Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia;2. Department of Medical Laboratory Sciences, Immune Responses in Different Diseases Research Group, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia;3. Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman, United Arab Emirates;4. Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Ha'il, Saudi Arabia;5. Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt;6. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, Assiut, Egypt;7. Department of Biology, Chemistry, Pharmacy, Free University of Berlin, Berlin, Germany;8. Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK |
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| Abstract: | Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti-inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer-407 (P-407). Rats were pretreated with BBR (25 and 50 mg/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P-407 (500 mg/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P-407-adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low-density lipoprotein receptor (LDL-R) and ATP-binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL-R, and ABCA1, and suppressed HMG-CoA reductase in P-407-administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro-inflammatory mediators (interleukin [IL]-6, IL-1β, tumor necrosis factor [TNF]-α, interferon-γ, IL-4 and IL-18) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) as well as NO and TNF-α release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR toward LPL, HMG-CoA reductase, LDL-R, PSK9, ABCA1, and E-NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E-NTPDase and E-ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation. |
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| Keywords: | berberine dyslipidemia E-NTPDase inflammation oxidative stress |
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