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口服白藜芦醇纳米脂质体通过Toll样受体3和含TIR结构域的接头诱导干扰素-β蛋白表达对动物模型高脂血症的影响

Effect of oral resveratrol-loaded nanoliposomes on hyperlipidemia via toll-like receptor 3 and TIR domain-containing adaptor inducing interferon-β protein expression in an animal model.

作者信息

Beheshtkhoo Nasrin, Jadidi Kouhbanani Mohammad Amin, Daghighi Seyed Mojtaba, Shakouri Nikjeh Maryam, Esmaeili Zahra, Khosravani Masood, Adabi Mahdi

机构信息

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Liposome Res. 2025 Sep;35(3):225-251. doi: 10.1080/08982104.2025.2476529. Epub 2025 Mar 18.

DOI:10.1080/08982104.2025.2476529
PMID:40098438
Abstract

Hyperlipidemia, a critical risk factor for various health conditions, necessitates innovative therapeutic strategies. Investigating the effectiveness of liposomal formulations in managing hyperlipidemia is essential. Resveratrol (RES)-loaded nanoliposomes present a promising new approach for hyperlipidemia treatment. In this study, we investigated the anti-hyperlipidemic potential of RES-loaded nanoliposomes in high-fat diet (HFD)-fed rats. The nanoliposomes were prepared using a thin-film hydration method. According to transmission electron microscopy (TEM) and dynamic light scattering (DLS) results, the mean size of prepared RES-loaded nanoliposomes were about 42 nm and 68 nm, respectively, with a zeta potential of -65.6 mV. The entrapment efficiency and loading content were 83.78% and 14.25%, respectively. Additionally, the RES-loaded nanoliposomes exhibited controlled release kinetics compared to the free RES form. Moreover, in a hyperlipidemic rat model induced by an HFD, orally administered RES-loaded nanoliposomes significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), while concurrently increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, liver damage induced by HFD was alleviated by RES-loaded nanoliposomes. The expression levels of Toll-like receptor 3 (TLR3) and TIR domain-containing adaptor-inducing interferon-β (TRIF) were assessed using fluorescence immunohistochemistry. Notably, RES-loaded nanoliposomes significantly reduced the expression of these protein. The effect of RES-loaded nanoliposomes was measured on body weight of HFD rats, demonstrting RES-loaded nanoliposomes hold promise for weight management. These findings underscore the potential of RES-loaded nanoliposomes as a safe and effective therapeutic option for hyperlipidemia.

摘要

高脂血症是多种健康状况的关键危险因素,需要创新的治疗策略。研究脂质体制剂在治疗高脂血症方面的有效性至关重要。负载白藜芦醇(RES)的纳米脂质体为高脂血症治疗提供了一种有前景的新方法。在本研究中,我们调查了负载RES的纳米脂质体对高脂饮食(HFD)喂养大鼠的抗高脂血症潜力。纳米脂质体采用薄膜水化法制备。根据透射电子显微镜(TEM)和动态光散射(DLS)结果,制备的负载RES的纳米脂质体的平均尺寸分别约为42nm和68nm,ζ电位为-65.6mV。包封率和载药量分别为83.78%和14.25%。此外,与游离RES形式相比,负载RES的纳米脂质体表现出控释动力学。此外,在由HFD诱导的高脂血症大鼠模型中,口服给予负载RES的纳米脂质体显著降低了总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)和甘油三酯(TG),同时提高了高密度脂蛋白胆固醇(HDL-C)水平。此外,负载RES的纳米脂质体减轻了HFD诱导的肝损伤。使用荧光免疫组织化学评估Toll样受体3(TLR3)和含TIR结构域的接头诱导干扰素-β(TRIF)的表达水平。值得注意的是,负载RES的纳米脂质体显著降低了这些蛋白的表达。测量了负载RES的纳米脂质体对HFD大鼠体重的影响,表明负载RES的纳米脂质体在体重管理方面具有前景。这些发现强调了负载RES的纳米脂质体作为高脂血症安全有效治疗选择的潜力。

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