槲皮素负载聚乙二醇脂体减轻四氧嘧啶诱导的糖尿病大鼠睾丸功能障碍：Kisspeptin/Neurokinin B/Dynorphin通路的作用

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-04-14 DOI:10.1016/j.taap.2025.117337

Mohamed Fouad Mansour , Amany Behairy , Mahmoud Mostafa , Tarek Khamis , Amira Ebrahim Alsemeh , Noura Mohammed Qenawy Ahmed , Mahran Mohamed Abd El-Emam

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引用次数: 0

摘要

糖尿病（DM）是一种慢性代谢紊乱，可导致严重并发症，包括睾丸功能障碍。这种功能障碍被认为是男性不育的重要原因。槲皮素是一种天然存在的具有多种生物功能的类黄酮，水溶性有限，生物利用度低。本研究旨在开发Que的生物利用制剂。通过将其包封在聚乙二醇化脂质体（Que-PEG-Lip）中，通过靶向Kisspeptin/Neurokinin B/Dynorphin/甾体生成信号通路，确定该制剂是否有效治疗四氧嘧啶诱导的睾丸损伤。将32只雄性Sprague Dawley大鼠随机分为4组：对照组、四氧嘧啶诱导的糖尿病伴睾丸功能障碍组（ALX）、ALX +二甲双胍组（MET）和ALX + Que-PEG-Lip组。结果显示，与ALX组相比，Que-PEG-Lip治疗ALX组小鼠血糖指数、血清生殖激素、睾丸抗氧化状态、睾丸Kiss-1、雄激素受体（AR）和增殖标记蛋白（ki67）免疫表达的变化明显改善。此外，Que-PEG-Lip治疗ALX组可调节Kisspeptin/Neurokinin B/Dynorphin/甾体生成途径基因表达。有趣的是，分子对接分析的结果显示Que具有很强的拮抗作用。关于kisspeptin， neurokinins和dynorphin受体。综上所述，Que-PEG-Lip通过调节下丘脑-垂体-性腺轴信号通路，减轻睾丸氧化应激，减轻四氧嘧啶诱导的糖尿病大鼠睾丸功能障碍。

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Quercetin-loaded PEGylated liposomes alleviate testicular dysfunction in alloxan-induced diabetic rats: The role of Kisspeptin/Neurokinin B/Dynorphin pathway

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Quercetin-loaded PEGylated liposomes alleviate testicular dysfunction in alloxan-induced diabetic rats: The role of Kisspeptin/Neurokinin B/Dynorphin pathway

Diabetes mellitus (DM) is a chronic metabolic disorder that can lead to serious complications, including testicular dysfunction. This dysfunction is considered a significant cause of male infertility. Quercetin (Que), a naturally existing flavonoid with versatile biological functions, has limited water solubility and low bioavailability. The current study was designed to develop a bioavailable formulation of Que. via encapsulating it in PEGylated liposomes (Que-PEG-Lip) and determine whether this formulation is effective in the treatment of alloxan-induced testicular injury via targeting Kisspeptin/Neurokinin B/Dynorphin/steroidogenesis signaling pathway. Thirty-two male Sprague Dawley rats were randomly divided into four groups: Control, alloxan-induced diabetes with testicular dysfunction (ALX), ALX + metformin (MET) and ALX + Que-PEG-Lip. The results showed that treatment of ALX group with Que-PEG-Lip significantly improved the alteration of glycemic index, serum reproductive hormones, testicular antioxidant status, testicular Kiss-1, androgen receptor (AR), and proliferation marker protein (ki67) immunoexpression in compared to ALX group. Moreover, the treatment of ALX group with Que-PEG-Lip regulated the Kisspeptin/Neurokinin B/Dynorphin/steroidogenesis pathway gene expression. Interestingly, the outcomes of the molecular docking analysis revealed a strong agonistic effect of Que. on the kisspeptin, neurokinin, and dynorphin receptors. In conclusion, Que-PEG-Lip mitigated the testicular dysfunction in alloxan-induced diabetic rats via regulation of hypothalamic-pituitary-gonadal axis signaling pathway and alleviation the testicular oxidative stress.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.