Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, PR China.
Eur J Pharmacol. 2010 Dec 15;649(1-3):390-7. doi: 10.1016/j.ejphar.2010.09.030. Epub 2010 Sep 21.
Berberine has hypoglycemic and hypolipidemic effects on diabetic rats. This study investigated the relationship between hypoglycemic and hypolipidemic effects of berberine and peroxisome proliferator-activated receptors (PPARs) and positive transcription elongation factor b (P-TEFb) (including cyclin-dependent kinase 9 (CDK9) and cyclin T1) in white adipose tissue of diabetic rats and RNA interference-treated 3T3-L1 cells. Berberine promoted differentiation and inhibited lipid accumulation of 3T3-L1 cells, further decreased PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression and decreased tumor necrosis factor α content in supernatants of both control and RNA interference-treated 3T3-L1 cells. After a 16-week induction with 35 mg/kg streptozotocin (i.p.) and high-carbohydrate/high-fat diet, diabetic rats were treated with 75, 150 and 300 mg/kg berberine and 100 mg/kg fenofibrate or 4 mg/kg rosiglitazone for another 16 weeks. Berberine decreased white adipose tissue to body weight ratio and adipocyte size and increased adipocyte number. Berberine upregulated PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expression in adipose tissue, decreased tumor necrosis factor α and free fatty acid content and increased lipoprotein lipase activity in serum and adipose tissue. Berberine modulated metabolic related PPARs expression and differentiation related P-TEFb expression in adipocytes, which are associated with its hypoglycemic and hypolipidemic effects.
小檗碱对糖尿病大鼠具有降血糖和降血脂作用。本研究探讨了小檗碱对糖尿病大鼠白色脂肪组织中过氧化物酶体增殖物激活受体（PPARs）和正转录伸长因子 b（P-TEFb）（包括细胞周期蛋白依赖性激酶 9（CDK9）和细胞周期蛋白 T1）与 RNA 干扰处理的 3T3-L1 细胞的降血糖和降血脂作用之间的关系。小檗碱促进了 3T3-L1 细胞的分化和脂质积累的抑制，进一步降低了对照组和 RNA 干扰处理的 3T3-L1 细胞上清液中 PPARα/δ/γ、CDK9 和细胞周期蛋白 T1mRNA 和蛋白表达，并降低了肿瘤坏死因子α的含量。在腹腔注射 35mg/kg 链脲佐菌素（STZ）和高碳水化合物/高脂肪饮食诱导 16 周后，用 75、150 和 300mg/kg 小檗碱及 100mg/kg 非诺贝特或 4mg/kg 罗格列酮对糖尿病大鼠进行治疗 16 周。小檗碱降低了白色脂肪组织与体重的比值和脂肪细胞的大小，并增加了脂肪细胞的数量。小檗碱上调了脂肪组织中 PPARα/δ/γ、CDK9 和细胞周期蛋白 T1mRNA 和蛋白表达，降低了血清和脂肪组织中肿瘤坏死因子α和游离脂肪酸含量，增加了脂蛋白脂肪酶活性。小檗碱调节了脂肪细胞中与代谢相关的 PPARs 表达和与分化相关的 P-TEFb 表达，这与其降血糖和降血脂作用有关。
