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姜黄素包裹的基于表没食子儿茶素没食子酸酯的纳米抗氧化剂通过抗氧化和抗炎疗法减轻结肠和肾脏炎症。

Curcumin-incorporated EGCG-based nano-antioxidants alleviate colon and kidney inflammation via antioxidant and anti-inflammatory therapy.

作者信息

Pan Qingqing, Xie Li, Zhu Huang, Zong Zhihui, Wu Di, Liu Rong, He Bin, Pu Yuji

机构信息

School of Preclinical Medicine, Chengdu University, Chengdu 610106, China.

Department of Pharmaceutical Engineering, Bengbu Medical University, Bengbu 233030, China.

出版信息

Regen Biomater. 2024 Oct 17;11:rbae122. doi: 10.1093/rb/rbae122. eCollection 2024.

DOI:10.1093/rb/rbae122
PMID:39539979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11558062/
Abstract

Natural remedies are gaining attention as promising approaches to alleviating inflammation, yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects. To overcome these limitations, we have developed a novel nano-antioxidant (EK) based on epigallocatechin gallate (EGCG) aimed at enhancing the oral and systemic bioavailability, as well as the anti-inflammatory efficacy, of curcumin (Cur) in conditions such as acute colon and kidney inflammation. EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine (K), resulting in the formation of EGCG oligomers. These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm. studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages, a key component in the body's inflammatory response. By efficiently encapsulating curcumin within these EK nanoparticles, we create Cur@EK, a formulation that demonstrates a synergistic anti-inflammatory effect. Specifically, Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-α and IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages, highlighting its potent anti-inflammatory properties. When administered either orally or intravenously, Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury. These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact, offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.

摘要

天然疗法作为缓解炎症的有前景的方法正受到关注,但其全部潜力常常受到生物利用度差和治疗效果欠佳等挑战的限制。为克服这些限制,我们基于表没食子儿茶素没食子酸酯(EGCG)开发了一种新型纳米抗氧化剂(EK),旨在提高姜黄素(Cur)在急性结肠和肾脏炎症等病症中的口服和全身生物利用度以及抗炎功效。EK通过EGCG与L-赖氨酸(K)之间简单的曼尼希反应合成,导致EGCG低聚物的形成。这些低聚物自发地自组装成具有球形形态且平均直径约为160nm的纳米颗粒。研究表明,EK纳米颗粒具有显著的自由基清除能力,并能有效调节巨噬细胞内的氧化还原过程,巨噬细胞是机体炎症反应的关键组成部分。通过将姜黄素有效地包裹在这些EK纳米颗粒中,我们制备了Cur@EK,一种具有协同抗炎作用的制剂。具体而言,Cur@EK在脂多糖刺激的巨噬细胞中显著降低促炎细胞因子TNF-α和IL-6的水平,同时增加抗炎细胞因子IL-10,突出了其强大的抗炎特性。当口服或静脉给药时,Cur@EK与游离姜黄素相比显示出更高的生物利用度,并在溃疡性结肠炎和急性肾损伤的小鼠模型中表现出明显的抗炎作用。这些发现表明,EK纳米抗氧化剂平台不仅提高了姜黄素的生物利用度,还增强了其治疗效果,为口服和全身炎症的治疗和管理提供了一条有前景的新途径。

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