PDF(Pubmed)
Abstract：
BACKGROUND: 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.
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.
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.
摘要：
背景：糖尿病性神经病（DN）被认为是由糖尿病（DM）引起的重要并发症。内质网(ER)应激加速DN的发病,抑制自噬并促进疾病进展。自噬是一种高度保守的机制，在减轻ER应激诱导的细胞死亡中至关重要。Chyrin,一种天然存在的类黄酮，可以在蜂蜜中找到丰富的，蜂胶,和各种植物提取物。尽管具有有利的属性，如作为抗氧化剂，抗过敏,抗炎,抗纤维化，和抗癌剂，chrysin表现出有限的生物利用度。当前的研究旨在生产一种更具生物利用度的chrysin形式，并发现施用chrysin如何改变雄性大鼠中四氧嘧啶引起的神经病变。
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。
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。
