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橙皮苷负载的 PVA/海藻酸钠水凝胶:靶向 NFκB/iNOS/COX-2/TNF-α 炎症信号通路。

Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway.

机构信息

Department of Molecular Oncology, Cancer Institute Women's Indian Association (WIA), Tamilnadu, India.

Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.

出版信息

Front Immunol. 2024 Apr 15;15:1347420. doi: 10.3389/fimmu.2024.1347420. eCollection 2024.

DOI:10.3389/fimmu.2024.1347420
PMID:38686374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11056547/
Abstract

INTRODUCTION

Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing.

METHODS

This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line.

RESULTS AND DISCUSSION

We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 μg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.

摘要

简介

皮肤损伤是一种常见的物理创伤形式,需要有效的治疗策略来加速伤口愈合过程。橙皮苷是一种存在于柑橘类水果中的生物类黄酮,具有多种药理学特性,包括抗菌、抗氧化、抗炎、抗凝和镇痛作用。本研究的主要目的是制备一种水凝胶,用于治疗皮肤状况,特别是伤口愈合。

方法

本研究介绍了一种制备聚维酮醇-海藻酸钠(PVA/A)共混物膜的方法,同时加入具有抗炎作用的橙皮苷(H),具有良好的伤口愈合能力。将包含 PVA/A 的均匀溶液层浇铸。通过在 30 kGy 的剂量下应用伽马辐射来实现交联和水凝胶特性的增强。将膜浸入橙皮苷(H)溶液中,促进药物的渗透和吸收。所得系统旨在以受控和持续的方式输送 H,这对于促进有效的伤口愈合至关重要。对获得的 PVA/AH 水凝胶进行了细胞毒性、抗氧化和自由基清除活性、抗炎和膜稳定性作用的评价。此外,还评估了其对 BJ-1 人正常皮肤细胞系的氧化应激和炎症标志物的作用。

结果与讨论

我们确定了 PVA/A(49%)和 PVA/AH(87%)的自由基清除活性、PVA/AH 对人红细胞膜溶血的抑制作用(81.97%和 84.34%)、低渗性(83.68%和 76.48%)和蛋白质变性(83.17%和 85.8%)的影响,分别与 250μg/ml 双氯芬酸(Dic.)和阿司匹林(Asp.)相比。此外,基因表达分析显示,与 LPS 刺激的 BJ-1 细胞相比,PVA/AH 水凝胶使与抗氧化和抗炎特性相关的基因表达增加,并使 TNFα、NFκB、iNOS 和 COX2 的表达分别下调 67%、52%、58%和 60%。橙皮苷的优势可以归因于其抗氧化和抗炎特性。将橙皮苷掺入水凝胶中为开发新型、安全、有效的伤口愈合策略提供了希望。这种创新方法有可能成为伤口愈合的解决方案,利用 PVA/AH 和伽马辐射的协同特性,可以将其结合起来建立橙皮苷的药物输送平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18cc/11056547/b9357e662e99/fimmu-15-1347420-g008.jpg
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