👤 Reem S Alruhaimi

Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS and inflammation in rats with acute hyperlipidemia. Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15. Poloxamer-407 elevated circulating cholesterol (CHOL), triglycerides (TG), very low-density lipoprotein (vLDL), and LDL, and reduced high-density lipoprotein (HDL)-C and lipoprotein lipase (LPL). ARB ameliorated the circulating lipids and LPL, and suppressed 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in rat liver and in vitro. Fatty acid synthase (FAS) in rat liver and its in vitro activity were suppressed by ARB, which also upregulated the LDL receptor (LDL-R) and ABCA1, and had no effect on ABCG5 and ABCG8 mRNA. ARB ameliorated liver malondialdehyde and nitric oxide and enhanced antioxidants in rats with dyslipidemia. Liver NF-κB p65 and blood inflammatory cytokines were increased in dyslipidemic rats, effects that were reversed by ARB. Moreover, ARB effectively suppressed lymphocyte E-NTPDase and E-ADA activities in dyslipidemic rats. The biochemical findings were supported by in silico data showing the affinity of ARB to bind LDL-R PCSK9 binding domain, HMGCR, FAS, and E-NTPDase. ARB possessed anti-dyslipidemia, anti-inflammatory, and antioxidant effects mediated via the modulation of CHOL and TG synthesis, LPL, lymphocyte E-NTPDase and E-ADA, and cytokine release in rats. Thus, ARB could be an effective agent to attenuate dyslipidemia and its associated OS and inflammation, pending further studies as well as clinical trials. Show less

Pluchea dioscoridis (L.) DC. is a flowering wild plant used traditionally in the treatment of rhematic disorders. This study investigated the phytochemical and in vitro radical scavenging activity (RSA), and in vivo anti-hyperlipidemic, antioxidant and anti-inflammatory properties of P. dioscoridis. The antihyperlipidemic efficacy was determined in a rat model of dyslipidemia. The extract and fractions of P. dioscoridis showed RSA with the ethyl acetate (EA) fraction exhibiting the most potent activity. The phytochemical analysis of P. dioscoridis EA fraction (PDEAF) led to the isolation of five compounds (lupeol, quercetin, lupeol acetate, stigmasterol, and syringic acid). To evaluate its anti-hyperlipidemic effect, three doses of PDEAF were supplemented to rats for 14 days and poloxamer-407 was administered on day 15 to induce dyslipidemia. All doses of PDEAF decreased plasma triglycerides, cholesterol, low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (vLDL-C), and increased plasma lipoprotein lipase (LPL). PDEAF upregulated hepatic LDL receptor and suppressed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, decreased lipid peroxidation and tumor necrosis factor (TNF)-α and enhanced reduced glutathione (GSH) and enzymatic antioxidants in dyslipidmeic rats. In silico findings revealed the binding affinity of the isolated compounds towards LPL, HMG-CoA reductase, and LDL receptor. In conclusion, P. dioscoridis is rich in phytoconstituents, exhibited RSA and its EA fraction effectively prevented acute dyslipidemia and its associated oxidative stress and inflammatory response. Show less

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. Show less