Mechanistic analysis for identifying the anti-diabetic effects of Cholic acid-loaded chitosan nanoparticles: An in vitro approach

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science Pub Date : 2024-10-10 DOI:10.1016/j.jksus.2024.103480

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Abstract

The identification of novel therapeutic agents using nanomedicine is critical in the fight against diabetes mellitus (DM). Cholic acid (CA) has shown potential in diabetes management, but its effectiveness is limited by poor solubility and stability. To overcome these challenges, CA was encapsulated in chitosan nanoparticles (CACNPs). The CACNPs had a negative zeta potential (ZP) of −13.6 ± 5.81 mV, which is an indication of good stability and potential for enhanced uptake by diseased cells. The average particle size (PS) measured by dynamic light scattering (DLS) was 169.8 ± 84.3 nm. The polydispersity index (PDI) was 0.220, indicating uniform particle size distribution. The drug loading capacity (DL%) of the CACNPs was 60.96 ± 0.9 %, whereas, the entrapment efficiency (EE%) was 69.19 ± 1.02 %. The MTT assay on 3 T3-L1 cells revealed a concentration-dependent effect on cell viability, with an IC₅₀ value of 766.0 ± 0.09 µg/ml. Furthermore, CACNPs demonstrated dose-dependent enhancement of glucose uptake in differentiated adipocytes, while at 500 µg/ml, they inhibited adipocyte differentiation, suggesting a potential role in adipogenesis inhibition. Quantitative PCR (qPCR) indicated positive modulation of glucose metabolism-related genes (PI3K, GLUT4, PPARg) upon treatment with CACNPs. These findings suggest that CACNPs could serve as a novel inhibitor of adipocyte differentiation and may influence key pathways in glucose metabolism, making them promising candidates for the management of DM.

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鉴定壳聚糖纳米颗粒抗糖尿病作用的机制分析：体外方法

利用纳米医学鉴定新型治疗药物对于防治糖尿病（DM）至关重要。胆酸（CA）已显示出治疗糖尿病的潜力，但其有效性受到溶解性和稳定性差的限制。为了克服这些挑战，人们将胆酸封装在壳聚糖纳米颗粒（CACNPs）中。CACNPs的负Zeta电位（ZP）为-13.6 ± 5.81 mV，这表明其具有良好的稳定性和被病变细胞吸收的潜力。用动态光散射（DLS）法测定的平均粒径（PS）为 169.8 ± 84.3 nm。多分散指数（PDI）为 0.220，表明粒度分布均匀。CACNPs 的载药量（DL%）为 60.96 ± 0.9 %，而夹带效率（EE%）为 69.19 ± 1.02 %。对 3 个 T3-L1 细胞进行的 MTT 检测显示，CACNPs 对细胞活力的影响与浓度有关，IC50 值为 766.0 ± 0.09 µg/ml。此外，CACNPs 还能剂量依赖性地增强分化脂肪细胞对葡萄糖的摄取，而当浓度为 500 µg/ml 时，CACNPs 则会抑制脂肪细胞的分化，这表明它在抑制脂肪生成方面具有潜在作用。定量 PCR（qPCR）表明，使用 CACNPs 处理后，葡萄糖代谢相关基因（PI3K、GLUT4、PPARg）会发生正向调节。这些研究结果表明，CACNPs 可作为一种新型的脂肪细胞分化抑制剂，并可能影响葡萄糖代谢的关键通路，因此有望成为治疗 DM 的候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of King Saud University - Science Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

2.60%

发文量

642

审稿时长

49 days

期刊介绍： Journal of King Saud University – Science is an official refereed publication of King Saud University and the publishing services is provided by Elsevier. It publishes peer-reviewed research articles in the fields of physics, astronomy, mathematics, statistics, chemistry, biochemistry, earth sciences, life and environmental sciences on the basis of scientific originality and interdisciplinary interest. It is devoted primarily to research papers but short communications, reviews and book reviews are also included. The editorial board and associated editors, composed of prominent scientists from around the world, are representative of the disciplines covered by the journal.