黄连素通过调节TLR-2/p-PI3K/p-AKT轴缓解大鼠子宫炎症

Berberine Alleviates Uterine Inflammation in Rats via Modulating the TLR-2/p-PI3K/p-AKT Axis

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INTERNATIONAL IMMUNOPHARMACOLOGY

影响因子:4.7

分区:医学2区 / 药学2区免疫学3区

发表日期:2024 Nov 15

作者: Rawan H Hareeri, Amal Hofni

DOI: 10.1016/j.intimp.2024.112931

摘要

子宫炎症影响美国8%的妇女和发展中国家的32%，多由炎症过度和氧化应激引起。这一状况严重影响妇女的健康、生产力和生活质量，并增加相关疾病的风险，导致医疗成本增加。当前研究重点在于天然抗氧化剂和抗炎药，尤其是黄连素（BBR），一种具有抗氧化、抗炎和抗凋亡活性的异喹啉生物碱。此次研究旨在探索BBR在实验条件下对由宫内注入碘（I2）引起的子宫炎症的潜在治疗效果。将雌性Sprague Dawley大鼠（n=6）分为五组：对照组、假手术组、I2组、I2+10 mg/kg BBR组和I2+25 mg/kg BBR组。与I2灌注相比，BBR治疗有效恢复正常子宫组织病理，降低IL-6、TNF-α、NF-κB、MCP1和MPO等炎症指标，同时降低MDA等氧化指标，升高过氧化氢酶（CAT）和超氧化物歧化酶（SOD）等抗氧化酶活性。还调节凋亡相关基因，Upreg Bcl-2，下调Bax。此外，BBR在I2处理的大鼠中抑制TLR-2、p-PI3K和p-AKT的表达。总之，BBR的治疗效果部分归因于其抗氧化、抗炎和抗凋亡作用，以及调控TLR-2/p-PI3K/p-AKT信号通路的能力。

Abstract

Uterine inflammation affects 8% of women in the United States and 32% in developing nations, often caused by uncontrolled inflammation and oxidative stress. This condition significantly impacts women's health, productivity, and quality of life, and increases the risk of related morbidities leading to higher healthcare costs. Research now focuses on natural antioxidants and anti-inflammatory, particularly berberine (BBR), an isoquinoline alkaloid known for its antioxidant, anti-inflammatory, and antiapoptotic activities. The present study sought to examine the potential therapeutic efficacy of BBR against uterine inflammation induced by the intrauterine infusion of an iodine (I2) mixture in an experimental setting. Female Sprague Dawley rats (n = 6) were divided into five groups, control, sham, I2, I2 and BBR 10 mg/kg, and I2 and BBR 25 mg/kg-treated groups. Compared to I2 infusion, BBR treatment effectively restored normal uterine histopathology and reduced inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor- kappa B (NF-κB), monocyte chemoattractant protein 1 (MCP1), and myeloperoxidase (MPO). It lowered oxidative markers like malondialdehyde (MDA), and increased antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). It balanced apoptotic genes by upregulating B-cell lymphoma 2 (Bcl-2) and downregulating Bcl-2-associated X protein (Bax). Furthermore, BBR reduced the expression of Toll-like receptor 2 (TLR-2), phosphorylated phosphatidylinositol 3‑kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) in the rats treated with intrauterine I2. Ultimately, the therapeutic benefits of BBR can be attributed, to some extent, to its antioxidant, anti-inflammatory, and antiapoptotic properties, in addition to its ability to modulate the TLR-2/p-PI3K/p-AKT axis.