糖尿病神经病变（DN）被认为是糖尿病（DM）引起的严重并发症。内质网 (ER) 应激会加速 DN 的发病，内质网应激会抑制自噬并导致疾病进展。自噬是一种高度保守的机制，对于减轻内质网应激诱导的细胞死亡至关重要。白杨素是一种天然存在的类黄酮，在蜂蜜、蜂胶和各种植物提取物中含量丰富。尽管白杨素具有抗氧化剂、抗过敏、抗炎、抗纤维化和抗癌等有利特性，但其生物利用度有限。目前的研究旨在生产一种生物利用度更高的白杨素，并探索白杨素如何改变雄性大鼠四氧嘧啶引起的神经病变。白杨素采用聚乙二醇化脂质体配制，以提高其生物利用度和配方。对白杨素聚乙二醇化脂质体 (Chr-PL) 进行了粒径、zeta 电位、多分散指数、透射电子显微镜和体外药物释放的表征。大鼠被分为四组：对照组、四氧嘧啶、二甲双胍和 Chr-PLs。为了确定 Chr-PLs 的抗糖尿病活性以及其改善 DN 的能力，进行了多项实验。这些包括测量乙酰胆碱酯酶、空腹血糖、胰岛素、依赖于内质网自噬或应激的基因以及组织病理学分析。根据结果，制备的 Chr-PLs 的平均粒径约为 134 nm。它们显示出均匀的粒径分布。最大包封率达到90.48±7.75%。与糖尿病大鼠相比，Chr-PLs 有效降低了 67.7% 的血糖水平，提高了 40% 的血清乙酰胆碱酯酶水平。此外，Chr-PLs 还抑制 ER 应激相关基因（ATF-6、CHOP、XBP-1、BiP、JNK、PI3K、Akt 和 mTOR）的表达达 33%、39.5%、32.2%、44.4%、40.4% 、 39.2%、39% 和 35.9%）。他们还将 miR-301a-5p 表达水平上调了 513%，将 miR-301a-5p 表达水平下调了 65%。他们还将坐骨神经中自噬标记物（AMPK、ULK1、Beclin 1 和 LC3-II 分别提高了 90.3%、181%、109% 和 78%）的表达。组织病理学分析还表明 Chr-PLs 抑制坐骨神经变性。研究结果表明 Chr-PLs 可能有助于通过调节 ER 应激和自噬来预防 DN。© 2024。作者。

Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats.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.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.The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.© 2024. The Author(s).