Berberine has been found to exhibit an array of pharmacological activities relating to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). The mechanism underlying these activites, however, is poorly understood. In the present study, female Sprague-Dawley (SD) rats were given oral letrozole to establish a model of insulin-resistant PCOS, and animals were then randomized into untreated or berberine-treated groups (400, 200, or 100 mg/kg). After 28 days, we measured homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) values in these animals. We further conducted H&E staining of ovarian tissues, assessed mRNA expression of glucose transporter 4 (GLUT4) via real time PCR, and used Western blotting to measure GLUT4 and PI3K/AKT and MAPK pathway protein levels. Berberine treatment was able to help restore HOMA-IR and ISI values to normal levels while simultaneously bolstering the expression of GLUT4. Normal ovarian morphology was also restored upon berberine treatment. We further found that 400 mg/kg berberine treatment was associated with activation of PI3K/AKT signaling and suppression of the MAPK pathway. In conclusion, berberine has the potential to reduce PCOS pathology and IR values in a rat model system through a mechanism linked to GLUT4 upregulation via PI3K/AKT activation and MAPK pathway suppression.

中文翻译：

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小ber碱可通过改善GLUT4降低PCOS大鼠的胰岛素抵抗：PI3K / AKT和MAPK通路的双重调控。

发现小碱具有一系列与降低血糖和治疗多囊卵巢综合征（PCOS）有关的药理活性。然而，人们对这些活性的机制知之甚少。在本研究中，对雌性Sprague-Dawley（SD）大鼠进行口服来曲唑建立胰岛素抵抗性PCOS模型，然后将动物随机分为未经治疗或经过小ber碱治疗的组（400、200或100 mg / kg） 。28天后，我们在这些动物中测量了胰岛素抵抗（HOMA-IR）和胰岛素敏感性指数（ISI）值的稳态模型评估。我们进一步进行了卵巢组织的H＆E染色，通过实时PCR评估了葡萄糖转运蛋白4（GLUT4）的mRNA表达，并使用Western印迹法测量了GLUT4和PI3K / AKT和MAPK途径蛋白水平。小ber碱治疗能够帮助将HOMA-IR和ISI值恢复至正常水平，同时增强GLUT4的表达。小碱治疗还可以恢复正常的卵巢形态。我们进一步发现400 mg / kg的小ber碱治疗与PI3K / AKT信号的激活和MAPK途径的抑制有关。总而言之，小ber碱具有通过与PI3K / AKT激活和MAPK途径抑制相关的GLUT4上调相关的机制来降低大鼠模型系统中PCOS病理学和IR值的潜力。我们进一步发现400 mg / kg小ber碱治疗与PI3K / AKT信号的激活和MAPK途径的抑制有关。总而言之，小ber碱具有通过与PI3K / AKT激活和MAPK途径抑制相关的GLUT4上调相关的机制来降低大鼠模型系统中PCOS病理学和IR值的潜力。我们进一步发现400 mg / kg的小ber碱治疗与PI3K / AKT信号的激活和MAPK途径的抑制有关。总之，小ber碱有可能通过与PI3K / AKT激活和MAPK途径抑制相关的GLUT4上调的机制，降低大鼠模型系统的PCOS病理学和IR值。