METHODS: Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs\' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis.
RESULTS: According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration.
CONCLUSIONS: The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.
方法:使用聚乙二醇化脂质体配制Chryin以提高其生物利用度和制剂。Chryin聚乙二醇化脂质体(Chr-PLs)的粒径直径进行表征,zeta电位,多分散指数,透射电子显微镜,和体外药物释放。大鼠分为四组:对照组,Alloxan,二甲双胍,和Chr-PLs。为了确定Cr-PLs的抗糖尿病活性,通过延伸,它改善DN的能力,进行了几个实验。这些包括测量乙酰胆碱酯酶,空腹血糖,胰岛素,依赖自噬或内质网应激的基因,和组织病理学分析。
结果:根据结果,制备的Chr-PLs表现出大约134nm的平均粒度。它们显示出颗粒大小的均匀分布。达到90.48±7.75%的最大包封效率。与糖尿病大鼠相比,Chr-PL可有效降低血糖水平67.7%,并升高血清乙酰胆碱酯酶水平40%。此外,Chr-PLs抑制ER应激相关基因的表达(ATF-6,CHOP,XBP-1,BiP,JNK,PI3K,Akt,mTOR下降33%,39.5%,32.2%,44.4%,40.4%,39.2%,39%,和35.9%,分别)。他们还将miR-301a-5p表达水平上调513%,并将miR-301a-5p表达水平下调65%。他们还促进了自噬标志物(AMPK,ULK1、Beclin1和LC3-II下降90.3%,181%,109%,78%,分别)在坐骨神经中。组织病理学分析还显示Chr-PLs抑制坐骨神经变性。
结论:研究结果表明,Chr-PLs可能通过调节内质网应激和自噬来保护DN。