研究动态
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小檗碱通过调节 TLR-2/p-PI3K/p-AKT 轴减轻大鼠子宫炎症。

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

发表日期:2024 Aug 14
作者: Rawan H Hareeri, Amal Hofni
来源: INTERNATIONAL IMMUNOPHARMACOLOGY

摘要:

子宫炎症影响着美国 8% 的女性和发展中国家的 32%,通常是由不受控制的炎症和氧化应激引起的。这种情况严重影响女性的健康、生产力和生活质量,并增加相关发病的风险,从而导致更高的医疗费用。目前的研究重点是天然抗氧化剂和抗炎剂,特别是小檗碱 (BBR),这是一种异喹啉生物碱,以其抗氧化、抗炎和抗细胞凋亡活性而闻名。本研究试图在实验环境中检查 BBR 对子宫内输注碘 (I2) 混合物引起的子宫炎症的潜在治疗效果。雌性 Sprague Dawley 大鼠 (n = 6) 分为五组:对照组、假手术组、I2 组、I2 和 BBR 10 mg/kg 组以及 I2 和 BBR 25 mg/kg 治疗组。与I2输注相比,BBR治疗有效恢复了正常的子宫组织病理学,并减少了炎症标志物,如白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、单核细胞趋化蛋白 1 (MCP1) 和髓过氧化物酶 (MPO)。它降低了丙二醛 (MDA) 等氧化标记物,并增加了抗氧化酶过氧化氢酶 (CAT) 和超氧化物歧化酶 (SOD)。它通过上调 B 细胞淋巴瘤 2 (Bcl-2) 和下调 Bcl-2 相关 X 蛋白 (Bax) 来平衡凋亡基因。此外,BBR 还降低了宫内 I2 治疗大鼠中 Toll 样受体 2 (TLR-2)、磷酸化磷脂酰肌醇 3 激酶 (p-PI3K) 和磷酸化蛋白激酶 B (p-AKT) 的表达。最终,除了调节 TLR-2/p-PI3K/p-AKT 轴的能力外,BBR 的治疗益处在某种程度上还可以归因于其抗氧化、抗炎和抗凋亡特性。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。
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.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.