Oxidative Stress, Inflammation, and Altered Lymphocyte E-NTPDase Are Implicated in Acute Dyslipidemia in Rats: Protective Role of Arbutin.

IF 4.3 3区医学 Q2 CHEMISTRY, MEDICINAL

Pharmaceuticals Pub Date : 2024-10-08 DOI:10.3390/ph17101343

Reem S Alruhaimi, Omnia E Hussein, Sulaiman M Alnasser, Mousa O Germoush, Meshal Alotaibi, Emad H M Hassanein, Mohamed El Mohtadi, Ayman M Mahmoud

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引用次数: 0

Abstract

Background/objectives: 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.

Methods: Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15.

Results: 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.

Conclusions: 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.

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氧化应激、炎症和淋巴细胞 E-NTPDase 改变与大鼠急性血脂异常有关：熊果苷的保护作用

背景/目的：血脂异常经常与各种疾病相关，其临床意义现已得到公认。炎症和氧化应激（OS）在血脂异常中的作用已得到公认。本研究评估了熊果苷（ARB）预防急性高脂血症大鼠血脂异常及其相关的OS和炎症的潜力：方法：大鼠口服 ARB 14 天，第 15 天腹腔注射 Poloxamer-407：结果：Poloxamer-407升高了循环胆固醇（CHOL）、甘油三酯（TG）、极低密度脂蛋白（vLDL）和低密度脂蛋白，降低了高密度脂蛋白（HDL）-C和脂蛋白脂肪酶（LPL）。ARB 可改善循环血脂和 LPL，并抑制大鼠肝脏和体外的 3-羟基-3-甲基戊二酰辅酶还原酶（HMGCR）。ARB抑制了大鼠肝脏中的脂肪酸合成酶（FAS）及其体外活性，还上调了低密度脂蛋白受体（LDL-R）和ABCA1，但对ABCG5和ABCG8 mRNA没有影响。ARB 可改善血脂异常大鼠肝脏中的丙二醛和一氧化氮，并增强抗氧化能力。血脂异常大鼠的肝脏 NF-κB p65 和血液中的炎性细胞因子增加，而 ARB 可逆转这些影响。此外，ARB 还能有效抑制血脂异常大鼠淋巴细胞 E-NTPDase 和 E-ADA 的活性。ARB与LDL-R PCSK9结合域、HMGCR、FAS和E-NTPDase的亲和力显示，这些生化研究结果得到了硅学数据的支持：ARB通过调节大鼠体内胆固醇和总胆固醇的合成、LPL、淋巴细胞E-NTPD酶和E-ADA以及细胞因子的释放，具有抗血脂异常、抗炎和抗氧化作用。因此，ARB 可能是减轻血脂异常及其相关操作系统和炎症的有效药物，有待进一步研究和临床试验。

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来源期刊

Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

6.10

自引率

4.30%

发文量

1332

审稿时长

6 weeks

期刊介绍： Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.