IF 6.7 1区 医学 Q1 CHEMISTRY, MEDICINAL
Qi Feng, Xiaoyue Yu, Junwei Xie, Fengxun Liu, Xiaonan Zhang, Shiyang Li, Yixue Wang, Shaokang Pan, Dongwei Liu, Zhangsuo Liu
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引用次数: 0

摘要

背景:连翘素(PHI)是连翘果实中的一种主要生物活性化合物,具有抗病毒、抗氧化、抗炎和降压等活性。目的:评估 PHI 对糖尿病肾病(DN)的治疗效果,并阐明其中的分子机制:方法:进行细胞活力测定和 RNA-seq 分析,以确定 PHI 调节 HG 诱导的 MPCs 的潜在机制。在 DN 细胞和小鼠模型中评估了 PHI 的疗效。使用酶联免疫吸附法测定细胞因子水平,并通过免疫印迹、免疫荧光和免疫组织化学染色分析关键信号通路的表达水平,包括TLR4/MyD88/NF-κB和PI3K/AKT/GSK3β以及下游效应因子:结果:在体外 HG 条件下,PHI 可降低 MPCs 中 IL-6、TNF-α、IL-1β、TLR4、MyD88、NF-κB 和裂解的 caspase-3 的表达水平,同时增强 PI3K、AKT、GSK3β(Ser9)和 pro-caspase-3 的磷酸化,从而抑制炎症反应并缓解细胞凋亡。此外,体内实验表明,用 PHI(50 毫克/千克)治疗 db/db 小鼠可有效改善肾功能,通过降低尿白蛋白与肌酐比值(UACR)、减轻荚膜细胞凋亡以及通过调节 TLR4/MyD88/NF-κB 和 PI3K/AKT/GSK3β 信号通路抑制炎症,从而减轻肾损伤:PHI通过干扰TLR4/MyD88/NF-κB和PI3K/AKT/GSK3β信号通路,抑制体外炎症和细胞凋亡,减轻db/db小鼠的糖尿病肾损伤。因此,本研究首次揭示了 PHI 是一种治疗 DN 的潜在新型药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Phillygenin improves diabetic nephropathy by inhibiting inflammation and apoptosis via regulating TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways.

Background: Phillygenin (PHI), a main bioactive compound found in the fruit of Forsythia suspensa, exhibits antiviral, antioxidant, anti-inflammatory, and antihypertensive activities. However, the molecular mechanisms underlying its effects on diabetic nephropathy (DN) remain unclear.

Purpose: To evaluate the therapeutic effects of PHI on DN and elucidate the molecular mechanisms involved.

Methods: Cell viability assays and RNA-seq analyses were performed to identify potential mechanisms through which PHI regulates HG-induced MPCs. The therapeutic efficacy of PHI was assessed in both DN cells and mouse models. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β along with downstream effectors were analyzed via immunoblotting, immunofluorescence, and immunohistochemical staining.

Results: PHI inhibited inflammatory responses and alleviated apoptosis by reducing the expression levels of IL-6, TNF-α, IL-1β, TLR4, MyD88, NF-κB, and cleaved caspase-3, while enhancing the phosphorylation of PI3K, AKT, GSK3β (Ser9), and pro-caspase-3 in MPCs under HG conditions in vitro. Additionally, in vivo experiments demonstrated that treatment with PHI (50 mg/kg) in db/db mice effectively improved renal function and attenuated kidney injury by reducing the urinary albumin-to-creatinine ratio (UACR), mitigating podocyte apoptosis, and inhibiting inflammatory via modulation of the TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways.

Conclusion: PHI inhibits inflammation and apoptosis in vitro and alleviates diabetic kidney injury in db/db mice by interfering TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways. Thus, this study reveals for the first time that PHI is a potential novel therapeutic agent for DN.

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来源期刊
Phytomedicine
Phytomedicine 医学-药学
CiteScore
10.30
自引率
5.10%
发文量
670
审稿时长
91 days
期刊介绍: Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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