Berberine8998 is a newly synthesized berberine derivative with better lipid-lowering activity and improved absorption. The objective of this study was to investigate the effects of berberine8998 on serum cholesterol and lipid levels in vivo and to examine the mechanisms involved. Hamsters on high-fat diet (HFD) were administered berberine or berberine8998 (50 mg·kg^-1·d^-1, ig) for 3 weeks. Berberine8998 administration significantly lowered the total cholesterol, triglycerides and LDL-C levels in HFD hamsters. Bioinformatics revealed that berberine and berberine8998 shared similar metabolic pathways and fatty acid metabolism was the predominant pathway. Western blot validation results showed that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and long-chain fatty acid-CoA ligase 1 (ACSL1), two proteins involved in fatty acid metabolism, were expressed differently in the berberine8998 group than in the untreated group and the berberine treatment group. Biochemistry results showed that berberine8998 significantly lowered the non-esterified fatty acid (NEFA) levels, which may lead to a reduction in TG levels in the berberine8998 treatment group and the differences observed in proteomics analyses. Pharmacokinetic analysis conducted in rats. After administration of berberine or berberine8998 (50 mg/kg, ig), berberine8998 exhibited a remarkably improved absorption with increasing bioavailability by 6.7 times compared with berberine. These findings suggest that berberine8998 lowers cholesterol and lipid levels via different mechanisms than berberine, and its improved absorption makes it a promising therapeutic candidate for the treatment of hypercholesterolemia and obesity.

中文翻译：

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蛋白质组学分析揭示了潜在的新靶蛋白，可降低Berberine8998的降脂作用。

小ber碱8998是新合成的小碱衍生物，具有更好的降脂活性和改善的吸收。这项研究的目的是调查小ber碱8998对体内血清胆固醇和脂质水平的影响，并探讨其中涉及的机制。给予高脂饮食（HFD）的仓鼠黄连素或小ber碱8998（50 mg·kg ^-1 ·d ^-1，ig）3周。施用Berberine8998可显着降低HFD仓鼠的总胆固醇，甘油三酸酯和LDL-C水平。生物信息学表明，小ber碱和小ber碱8998共有相似的代谢途径，而脂肪酸代谢是主要途径。Western blot验证结果表明，过氧化物酶体酰基辅酶A氧化酶1（ACOX1）和长链脂肪酸-CoA连接酶1（ACSL1）是两种参与脂肪酸代谢的蛋白质，其在小ber碱8998组中的表达与未处理组中的表达不同和小ber碱治疗组。生化结果显示，小ber碱8998显着降低了非酯化脂肪酸（NEFA）的水平，这可能导致小ber碱8998治疗组的TG水平降低，并且在蛋白质组学分析中观察到差异。在大鼠中进行药代动力学分析。与小ber碱相比，小administration碱或小ber碱8998（50 mg / kg，ig）给药后，小ber碱8998的吸收显着改善，生物利用度提高了6.7倍。这些发现表明，小ber碱8998通过与小ber碱不同的机制降低胆固醇和脂质水平，并且其改善的吸收使其成为治疗高胆固醇血症和肥胖症的有希望的治疗候选者。