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基于 LC-MS 的代谢组学分析及载壳聚糖纳米粒子的贯叶连翘配方在糖尿病大鼠中的伤口愈合活性。

LC-MS based metabolic profiling and wound healing activity of a chitosan nanoparticle-loaded formula of Teucrium polium in diabetic rats.

机构信息

Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Biomed Pharmacother. 2023 Dec;168:115626. doi: 10.1016/j.biopha.2023.115626. Epub 2023 Oct 16.


DOI:10.1016/j.biopha.2023.115626
PMID:37852098
Abstract

Healing of wounds is the most deteriorating diabetic experience. Felty germander (Teucrium polium) possesses antioxidant, anti-inflammatory and antimicrobial activities that could accelerate wound healing. Further, nanohydrogels help quicken healing and are ideal biomaterials for drug delivery. In the current study, the chemical profiling, and standardization of T. polium methanolic extract by LC-ESI/TOF/MS/MS and quantitative HPLC-DAD analyses were achieved. The wound healing enhancement in diabetic rats by T. polium nanopreparation (TP-NP) as chitosan nanogel (CS-NG) and investigating the potential mechanisms were investigated. The prepared hydrogel-based TP-NP were characterized with respect to particle size, zeta potential, pH, viscosity, and release of major components. LC-ESI/TOF/MS/MS metabolomic profiling of T. polium revealed the richness of the plant with phenolic compounds, particularly flavonoids. In addition, several terpenoids were detected. Kaempferol content of T. polium was estimated to be 7.85 ± 0.022 mg/ g of dry extract. The wound healing activity of TP-NP was explored in streptozotocin-induced diabetic rats. Diabetic animals were subjected to surgical wounding (1 cm diameter). Then they were divided in 5 groups (10 each). These included Group 1 (untreated control rats), Group 2 received the vehicle of CS-NG; Group 3 (0.5 g of TP prepared in hydrogel), Group 4 (0.5 g of TP-NP), Group 5 represented a positive control treated with 0.5 g of a commercial product. All treatments were applied topically for 21 days. Application of TP-NP on skin wounds of diabetic animals accelerated the healing process as evidenced by epithelium regeneration, formation of granulation tissue followed by epidermal proliferation, along with keratinization as verified by H&E. This was confirmed through enhanced collagen synthesis, as shown by raised hydroxyproline content and Col1A1 gene expression. Moreover, TP-NP significantly alleviated wound oxidative burst and diminished the expressions of inflammatory biomarkers. Meanwhile, TP-NP could enhance the expressions of transforming growth factor beta1 (TGF-β1), in addition to the angiogenic markers; vascular endothelia growth factor A (VEGFA) and platelet-derived growth factor receptor alpha (PDGFRα). Collectively, chitosan nanogel of T. polium accelerates wound healing in diabetic rats, which could be explained - at least partly - through alleviating oxidative stress and inflammation coupled with pro-angiogenic capabilities.

摘要

伤口愈合是糖尿病患者最恶化的经历。费蒂天竺葵(Teucrium polium)具有抗氧化、抗炎和抗菌活性,可加速伤口愈合。此外,纳米水凝胶有助于加速愈合,是药物输送的理想生物材料。在本研究中,通过 LC-ESI/TOF/MS/MS 和定量 HPLC-DAD 分析实现了 T. polium 甲醇提取物的化学特征分析和标准化。通过 chitosan 纳米凝胶(CS-NG)研究了 T. polium 纳米制剂(TP-NP)对糖尿病大鼠伤口愈合的增强作用及其潜在机制。制备的基于水凝胶的 TP-NP 进行了粒径、zeta 电位、pH 值、粘度和主要成分释放的特性研究。LC-ESI/TOF/MS/MS 代谢组学分析表明,该植物富含酚类化合物,特别是类黄酮。此外,还检测到几种萜类化合物。估计 T. polium 中槲皮素的含量为 7.85±0.022mg/g 干提取物。研究了 TP-NP 对链脲佐菌素诱导的糖尿病大鼠的伤口愈合活性。糖尿病动物接受了手术性创伤(直径 1cm)。然后将它们分为 5 组(每组 10 只)。这些包括第 1 组(未处理的对照组大鼠)、第 2 组接受 CS-NG 的载体;第 3 组(0.5g 以水凝胶形式制备的 TP)、第 4 组(0.5g TP-NP)、第 5 组为用 0.5g 商业产品治疗的阳性对照组。所有治疗均在 21 天内局部应用。TP-NP 在糖尿病动物的皮肤伤口上的应用加速了愈合过程,上皮再生、肉芽组织形成以及随后的表皮增殖,以及 H&E 证实的角化都证明了这一点。这通过增加羟脯氨酸含量和 Col1A1 基因表达证实了胶原蛋白合成的增强。此外,TP-NP 显著减轻了伤口氧化爆发,并降低了炎症生物标志物的表达。同时,TP-NP 可以增强转化生长因子β1(TGF-β1)的表达,以及血管内皮生长因子 A(VEGFA)和血小板衍生生长因子受体α(PDGFRα)等血管生成标志物的表达。总的来说,TP-NP 壳聚糖纳米凝胶可加速糖尿病大鼠的伤口愈合,这至少可以部分解释为通过减轻氧化应激和炎症以及促进血管生成能力。

相似文献

[1]
LC-MS based metabolic profiling and wound healing activity of a chitosan nanoparticle-loaded formula of Teucrium polium in diabetic rats.

Biomed Pharmacother. 2023-12

[2]
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[3]
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[4]
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[5]
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[6]
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J Complement Integr Med. 2022-6-1

[7]
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[8]
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[9]
[Effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats].

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[10]
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引用本文的文献

[1]
Chitosan-Based Nanoformulations: Preclinical Investigations, Theranostic Advancements, and Clinical Trial Prospects for Targeting Diverse Pathologies.

AAPS PharmSciTech. 2024-11-5

[2]
Emerging Nanotherapeutic Approaches for Diabetic Wound Healing.

Int J Nanomedicine. 2024

[3]
Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Venom.

Anticancer Agents Med Chem. 2024

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