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载姜黄素固体脂质纳米粒凝胶的抗银屑病活性评价:通过 NF-κB 信号通路的设计、表征和机制研究。

Assessment of anti-psoriatic activity of bakuchiol-loaded solid lipid nanoparticles-based gel: design, characterization, and mechanistic insight via NF-kB signaling pathway.

机构信息

Department of Botanical & Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2023 Sep;396(9):2105-2125. doi: 10.1007/s00210-023-02445-1. Epub 2023 Mar 17.

Abstract

The aim of the current study is to evaluate the anti-psoriatic potential of bakuchiol (Bak) loaded solid lipid nanoparticles (SLNs) via modulating inflammatory and oxidative pathways. Bak-loaded SLNs were prepared using hot homogenization method and characterized by various spectroscopic techniques. Bak-SLNs suspension was formulated into gel using Carbopol. Different in vivo assays were executed to explore the role of inflammatory markers and oxidative enzymes in psoriasis. DLS (dynamic light scattering) analysis showed suitable particle size, zeta potential, and polydispersity index (PDI) of developed formulation. TEM (transmission electron microscopy) reveal the spherical shape of Bak-SLNs particles. The release studies confirmed the sustained release of Bak-SLNs-based gel. UV-B-induced psoriatic Wistar rat model showed significant anti-psoriatic effect of Bak via regulating inflammatory markers (NF-kB, IL-6, IL-4, and IL-10) and levels of anti-oxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-S-transferase (GST). Furthermore, RT-qPCR analysis confirms that Bak downregulates the expression of inflammatory markers, while histology and immunohistology results also confirm the anti-psoriatic effect of Bak. The study indicates that Bak-loaded SLNs-based gel significantly downregulates the level of cytokines and interleukins involve in NF-kB signaling cascade; hence, it can prove to be a novel therapeutic approach to cure psoriasis.

摘要

本研究旨在通过调节炎症和氧化途径来评估花椒酚(Bak)负载固体脂质纳米粒(SLNs)的抗银屑病潜力。采用热熔匀化法制备 Bak-SLNs,并采用多种光谱技术对其进行表征。将 Bak-SLNs 混悬液用 Carbopol 制成凝胶。进行了不同的体内实验来探究炎症标志物和氧化酶在银屑病中的作用。DLS(动态光散射)分析显示,所开发的制剂具有合适的粒径、Zeta 电位和多分散指数(PDI)。TEM(透射电子显微镜)显示 Bak-SLNs 颗粒呈球形。释放研究证实了 Bak-SLNs 基凝胶的持续释放。UV-B 诱导的银屑病 Wistar 大鼠模型表明,Bak 通过调节炎症标志物(NF-kB、IL-6、IL-4 和 IL-10)和抗氧化酶水平(超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)和谷胱甘肽-S-转移酶(GST))发挥显著的抗银屑病作用。此外,RT-qPCR 分析证实 Bak 下调了炎症标志物的表达,而组织学和免疫组织化学结果也证实了 Bak 的抗银屑病作用。该研究表明,Bak 负载的 SLNs 基凝胶可显著下调参与 NF-kB 信号级联的细胞因子和白细胞介素的水平;因此,它可能成为治疗银屑病的一种新的治疗方法。

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