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姜黄重建纳米囊泡的开发与评价及其在肥胖多方位干预中的应用。

Development and Evaluation of Reconstructed Nanovesicles from Turmeric for Multifaceted Obesity Intervention.

机构信息

Department of Biological Engineering, College of Ocean Food and Biological Engineering, Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Jimei University, Xiamen, Fujian 361021, China.

Engineering Research Center of Natural Cosmeceuticals College of Fujian Province, Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen, Fujian 361018, China.

出版信息

ACS Nano. 2024 Aug 27;18(34):23117-23135. doi: 10.1021/acsnano.4c05309. Epub 2024 Aug 17.

DOI:10.1021/acsnano.4c05309
PMID:39153188
Abstract

The escalating prevalence of obesity poses significant health challenges due to its direct association with various diseases. Most existing medications, such as appetite suppressants and fat absorption inhibitors, suffer from limited effectiveness and undesirable side effects. Here, inspired by the versatile metabolic effects of turmeric, we developed a naturally derived nanoformulation of "Reconstructed Turmeric-derived Nanovesicles (Rec-tNVs)" for obesity treatment. Employing quantitative nanoflow cytometry, a four-orders-of-magnitude increase in curcumin content (∼10 molecules per particle) was identified in individual Rec-tNVs compared to their ultracentrifugation-isolated counterparts. Rec-tNVs, featuring highly aggregated curcumin arrangements and other coencapsulated bioactive compounds, demonstrated a dose-dependent lipid-lowering effect in mature 3T3-L1 cells by promoting lipolysis, suppressing lipogenesis, inducing adipocyte browning, and triggering apoptosis after internalization via multiple pathways. experiments revealed that Rec-tNVs alleviated obesity more effectively than free curcumin and achieved weight reductions of 18.68 and 14.56% through intragastric and subcutaneous delivery, respectively, in high-fat-diet mouse models over a four-week treatment period. These effects were attributed to targeted actions on adipose tissues and systemic impacts on metabolism and gut microbiota composition. Overall, this study underscores the multifaceted antiobesity efficacy of Rec-tNVs, and offers a promising paradigm for developing plant-derived nanovesicle-based therapeutics.

摘要

肥胖症的患病率不断上升,由于其与各种疾病的直接关联,给健康带来了重大挑战。大多数现有的药物,如食欲抑制剂和脂肪吸收抑制剂,都存在疗效有限和不良副作用的问题。在这里,受姜黄多功能代谢作用的启发,我们开发了一种天然衍生的“重建姜黄衍生纳米囊泡(Rec-tNVs)”用于肥胖症治疗的纳米制剂。通过定量纳米流细胞术,我们发现单个 Rec-tNVs 中的姜黄素含量增加了四个数量级(∼每个粒子 10 个分子),而与它们的超速离心分离物相比。Rec-tNVs 具有高度聚集的姜黄素排列和其他共包封的生物活性化合物,通过促进脂肪分解、抑制脂肪生成、诱导脂肪细胞棕色化和在通过多种途径内化后触发细胞凋亡,在成熟的 3T3-L1 细胞中表现出剂量依赖性的降脂作用。体内实验表明,Rec-tNVs 比游离姜黄素更有效地缓解肥胖症,在高脂肪饮食的小鼠模型中,通过灌胃和皮下给药,分别在四周的治疗期内实现了 18.68%和 14.56%的体重减轻。这些效果归因于对脂肪组织的靶向作用以及对代谢和肠道微生物组成的全身影响。总的来说,这项研究强调了 Rec-tNVs 的多方面抗肥胖功效,并为开发基于植物衍生纳米囊泡的治疗方法提供了有前途的范例。

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