小檗碱-肉桂酸共晶改善高脂血症的作用可能通过PI3K/AKT/mTOR/SREBP-1信号通路调控。

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Wenheng Gao, Yunlong Li, Lihua Chen, Wenshuo Yang, Yong He, Ye Yang, Dengke Yin, Song Tan
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引用次数: 0

摘要

高脂血症是一种常见的慢性疾病,其特征是血液中的脂质水平升高。有证据表明,小檗碱(BBR)可能有利于治疗高脂血症。然而,其低肠道生物利用度限制了其潜在的治疗作用。在本研究中,我们探索了由CA和BBR自组装而成的具有较高肠道生物利用度的小檗碱-肉桂酸共晶(BBR-CA)的作用及其机制。在小鼠实验中,BBR-CA显示出降低高脂肪饮食动物体重增加和肝脏脂质积累的能力。为了进一步表征这种效应的分子基础,我们通过用游离脂肪酸治疗人肝癌细胞(HepG2)建立了高脂血症细胞模型。与我们的体内实验类似,BBR-CA也减少了游离脂肪酸诱导的HepG2细胞的脂质积累。我们假设BBR-CA可能通过调节固醇调节元件结合蛋白-1 (SREBP-1)起作用,SREBP-1是调节脂质合成的关键因子,并且BBR-CA处理确实抑制了SREBP-1蛋白的表达,导致其下游蛋白硬脂酰辅酶a去饱和酶1和乙酰辅酶a羧化酶的表达减少。此外,BBR-CA抑制了磷脂酰肌醇3-激酶(PI3K)、AKT和哺乳动物雷帕霉素靶蛋白(mTOR)的磷酸化,导致细胞核中SREBP-1活性降低,PI3K激动剂recilisib和抑制剂LY294002分别逆转和增强了PI3K的磷酸化。综上所述,我们的研究结果表明,BBR-CA可能通过调节PI3K/AKT/mTOR信号通路发挥作用,导致SREBP-1的核表达减少,以及硬脂酰辅酶a去饱和酶1和乙酰辅酶a羧化酶的表达减少,从而缓解高脂血症。需要进一步的实验验证来证实这些结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Berberine-cinnamic acid co-crystal effect in ameliorating hyperlipidemia might be regulated through the PI3K/AKT/mTOR/SREBP-1 signaling pathway.

Hyperlipidemia is a common chronic disease characterized by elevated levels of lipids in the blood. There is some evidence that suggests that berberine (BBR) might be beneficial for the treatment of hyperlipidemia. However, its low intestinal bioavailability limits its potential therapeutic action. In the present study, we explored the effect and the underlying mechanism of berberine-cinnamic acid co-crystal (BBR-CA), which is self-assembled from CA and BBR and displays a high intestinal bioavailability. In mice, BBR-CA showed the ability to decrease body weight gain and hepatic lipid accumulation in animals fed a high-fat diet. To further characterize the molecular basis of this effect, we established a hyperlipidemia cell model by treating human hepatocellular carcinoma cells (HepG2) with free fatty acids. Similarly to our in vivo experiments, lipid accumulation in free fatty acids-induced HepG2 cells was also reduced by BBR-CA. We hypothesized that BBR-CA might act through the regulation of sterol regulatory element-binding proteins-1 (SREBP-1), a key factor regulating lipid synthesis, and, indeed, SREBP-1 protein expression was inhibited by BBR-CA treatment, resulting in the decreased expression of its downstream proteins stearoyl-CoA desaturase 1 and acetyl-CoA carboxylase. Furthermore, the phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) was inhibited by BBR-CA, contributing to decreased active SREBP-1 in the nucleus, and was reversed and enhanced by the PI3K agonist recilisib and inhibitor LY294002, respectively. Taken together, our results suggest that BBR-CA could function by modulating the PI3K/AKT/mTOR signaling pathway, resulting in decreased nuclear expression of SREBP-1, as well as reduced expression of stearoyl-CoA desaturase 1 and acetyl-CoA carboxylase, thus alleviating hyperlipidemia. Further experimental validation is required to confirm these results.

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来源期刊
FEBS Open Bio
FEBS Open Bio BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
5.10
自引率
0.00%
发文量
173
审稿时长
10 weeks
期刊介绍: FEBS Open Bio is an online-only open access journal for the rapid publication of research articles in molecular and cellular life sciences in both health and disease. The journal''s peer review process focuses on the technical soundness of papers, leaving the assessment of their impact and importance to the scientific community. FEBS Open Bio is owned by the Federation of European Biochemical Societies (FEBS), a not-for-profit organization, and is published on behalf of FEBS by FEBS Press and Wiley. Any income from the journal will be used to support scientists through fellowships, courses, travel grants, prizes and other FEBS initiatives.
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