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载有咖啡酸苯乙酯的聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒促进糖尿病大鼠伤口愈合

Caffeic Acid Phenethyl Ester Loaded PEG-PLGA Nanoparticles Enhance Wound Healing in Diabetic Rats.

作者信息

Nasrullah Mohammed Z

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Antioxidants (Basel). 2022 Dec 27;12(1):60. doi: 10.3390/antiox12010060.

DOI:10.3390/antiox12010060
PMID:36670922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9854644/
Abstract

Delayed wound healing is a serious complication of diabetes and a main reason for foot amputation. Caffeic acid phenethyl ester (CAPE) is a main active constituent of honeybee propolis with reported appealing pharmacological activities. In the current study, CAPE was loaded onto PEG-PLGA nanoparticles and showed a particle size of 198 ± 7.3 nm and polydispersity index of 0.43 ± 0.04. An in vivo study was performed to appraise the wound-healing activity of CAPE-loaded PEG-PLGA nanoparticles (CAPE-NPs) in diabetic rats. Wound closure was significantly accelerated in rats treated with CAPE-NPs. This was confirmed via histological examinations of skin tissues that indicated expedited healing and enhanced collagen deposition. This was accompanied by observed antioxidant activity as evidenced by the prevention of lipid peroxidation and the exhaustion of superoxide dismutase (SOD) and catalase (CAT) activities. In addition, CAPE-NPs showed superior anti-inflammatory activity as compared with the regular formula of CAPE, as they prevented the expression of interleukin-6 (IL-6) as well as tumor necrosis-alpha (TNF-α). The pro-collagen actions of CAPE-NPs were highlighted by the enhanced hyroxyproline content and up-regulation of Col 1A1 mRNA expression. Furthermore, the immunohistochemial assessment of skin tissues indicated that CAPE-NPs enhance proliferation and angiogenesis, as shown by the increased expression of transforming growth factor β1 (TGF-β1) and platelet-derived growth factor subunit B (PDGF-B). In conclusion, CAPE-loaded PEG-PLGA nanoparticles possess potent healing effects in diabetic wounds. This is mediated, at least partially, by its antioxidant, anti-inflammatory, and pro-collagen as well as angiogenic activities.

摘要

伤口愈合延迟是糖尿病的一种严重并发症,也是足部截肢的主要原因。咖啡酸苯乙酯(CAPE)是蜜蜂蜂胶的主要活性成分,具有显著的药理活性。在本研究中,CAPE被负载到聚乙二醇-聚乳酸-羟基乙酸共聚物(PEG-PLGA)纳米颗粒上,其粒径为198±7.3纳米,多分散指数为0.43±0.04。进行了一项体内研究,以评估负载CAPE的PEG-PLGA纳米颗粒(CAPE-NPs)对糖尿病大鼠的伤口愈合活性。用CAPE-NPs治疗的大鼠伤口闭合明显加快。这通过对皮肤组织的组织学检查得到证实,结果表明愈合加快且胶原蛋白沉积增加。同时观察到其抗氧化活性,表现为脂质过氧化受到抑制,超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性耗尽。此外,与CAPE常规配方相比,CAPE-NPs显示出更强的抗炎活性,因为它们抑制了白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达。CAPE-NPs的促胶原蛋白作用表现为羟脯氨酸含量增加和Col 1A1 mRNA表达上调。此外,皮肤组织的免疫组织化学评估表明,CAPE-NPs增强了增殖和血管生成,表现为转化生长因子β1(TGF-β1)和血小板衍生生长因子亚基B(PDGF-B)表达增加。总之,负载CAPE的PEG-PLGA纳米颗粒对糖尿病伤口具有显著的愈合作用。这至少部分是由其抗氧化、抗炎、促胶原蛋白以及血管生成活性介导的。

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