Objective

Palmatine (PAL) is a natural isoquinoline alkaloid that has been widely used in the pharmaceutical field. The current study aimed to investigate the function of PAL in improving hyperlipidemia induced by high-fat diet (HFD) in rats.

Methods

Biochemical analysis of triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDLC) was performed on rats. Total bile acid (TBA) and stool TC and TBA were also measured to assess the changes in total bile acid excretion. RT-qPCR was employed to detect the expression of genes related to bile acid metabolism, and the Western blot assay was used to detect the levels of CYP7A1, ZO-1, ZO-2, and Claudin-1. The siRNA experiment was employed to further investigate whether PAL regulated CYP7A1 through PPARα. Lipopolysaccharide (LPS) and FITC-dextran (FD-4) were also tested to assess the intestinal permeability.

Results

AL-treated rats had lower TC, TG, LDL-C levels, lower serum TBA levels, and increased fecal TBA and TC levels. Furthermore, CYP7A1 protein expression was up-regulated in PAL-treated rats. Additionally, PAL regulated bile acid metabolism by up-regulating the expression of CYP7A1 and PPARα and down-regulating the expression of FXR. Besides, the area of plasma FD-4 and LPS content in the PAL group were reduced, and the expression of proteins ZO-1, ZO-2 and Claudin-1 related to intestinal permeability was increased.

Conclusion

All in all, PAL could mediate the PPARα-CYP7A1 pathway to maintain the balance of intestinal flora, regulate the bile acid metabolism, and reduce the blood lipids of rats, thereby protecting against hyperlipidemia.

中文翻译：

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棕榈碱调节胆汁酸循环代谢并维持肠道菌群平衡，以维持稳定的肠屏障。

目的

棕榈碱（PAL）是一种天然的异喹啉生物碱，已广泛用于制药领域。目前的研究旨在研究PAL在改善高脂饮食（HFD）引起的大鼠高脂血症中的功能。

方法

在大鼠上进行了甘油三酸酯（TG），总胆固醇（TC），低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL C）的生化分析。还测量了总胆汁酸（TBA）和粪便TC和TBA，以评估总胆汁酸排泄的变化。RT-qPCR用于检测与胆汁酸代谢相关的基因的表达，Western印迹法用于检测CYP7A1，ZO-1，ZO-2和Claudin-1的水平。siRNA实验用于进一步研究PAL是否通过PPARα调节CYP7A1。还测试了脂多糖（LPS）和FITC-葡聚糖（FD-4）以评估肠通透性。

结果

经AL治疗的大鼠的TC，TG，LDL-C水平较低，血清TBA水平较低，而粪便TBA和TC水平升高。此外，CYP7A1蛋白表达在PAL治疗的大鼠中上调。此外，PAL通过上调CYP7A1和PPARα的表达并下调FXR的表达来调节胆汁酸代谢。此外，PAL组血浆FD-4和LPS含量减少，与肠通透性相关的蛋白ZO-1，ZO-2和Claudin-1的表达增加。

结论

总而言之，PAL可以介导PPARα-CYP7A1通路，以维持肠道菌群的平衡，调节胆汁酸的代谢，并降低大鼠的血脂，从而预防高脂血症。