berberine通过调节TLR-2/P-PI3K/P-AKT轴来减轻大鼠的子宫炎症
Berberine Alleviates Uterine Inflammation in Rats via Modulating the TLR-2/p-PI3K/p-AKT Axis
影响因子:4.70000
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
摘要
子宫炎症通常由不受控制的炎症和氧化应激引起的美国影响8％的女性和发展中国家的32％。这种情况显着影响妇女的健康，生产力和生活质量，并增加了相关病毒的风险，从而导致更高的医疗保健费用。现在的研究重点是天然抗氧化剂和抗炎药，尤其是Berberine（BBR），这是一种以抗氧化剂，抗炎和抗凋亡活性而闻名的异喹啉生物碱。本研究试图检查BBR在实验环境中碘（I2）混合物的子宫内输注引起的子宫炎症的潜在治疗功效。雌性Sprague Dawley大鼠（n = 6）分为五组，Sham，I2，I2和BBR 10 mg/kg，I2和BBR 25 mg/kg处理的组。与I2输注相比，BBR治疗有效地恢复了正常的子宫组织病理学和炎症标记，例如白介素6（IL-6），肿瘤坏死因子 - α（TNF-α），核因子-KAPPA B（NF-κB）B（NF-κB），单激素化学涂层蛋白质1（MCP1）（MCP1）和Myporoxic（M.Myoperoxid）。它降低了氧化标记，如丙二醛（MDA），并增加了抗氧化剂酶过氧化氢酶（CAT）和超氧化物歧化酶（SOD）。它通过上调B细胞淋巴瘤2（BCL-2）并下调Bcl-2相关的X蛋白（BAX）来平衡凋亡基因。此外，BBR降低了类似受体样受体2（TLR-2），磷酸化的磷脂酰肌醇3-激酶（P-PI3K）和磷酸化的蛋白激酶B（P-AKT）的表达，并在接受宫内I2的大鼠中。最终，除了调节TLR-2/P-PI3K/P-AKT轴的能力外，BBR的治疗益处还可以在某种程度上归因于其抗氧化剂，抗炎和抗凋亡特性。
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.