Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E‐NTPDase in acute hyperlipidemia

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.