Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.
Eur J Pharmacol. 2011 Jan 25;651(1-3):168-75. doi: 10.1016/j.ejphar.2010.10.076. Epub 2010 Nov 27.
Berberine is an isoquinoline alkaloid, occurring in nature as the main constituent of several plants with medicinal use in kidney stone disease. This work was undertaken to evaluate its antiurolithic potential and explore the possible underlying mechanism(s). Berberine was tested in vitro for the antioxidant effect and in vivo for diuretic and antiurolithic effects on an animal model of calcium oxalate urolithiasis. Berberine exhibited concentration-dependent (50-150μg/ml) antioxidant effect against ferrous-ascorbate induced lipid peroxidation in rat kidney homogenate with potency slightly higher than the reference antioxidant, butylated hydroxytoluene. In Wistar rats, berberine (5-20mg/kg) increased urine output accompanied by increased pH and Na(+) and K(+) excretion and decreased Ca(2+) excretion, similar to hydrochlorothiazide. In an animal model of calcium oxalate urolithiasis developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water, berberine (10mg/kg) prevented as well as eliminated calcium oxalate crystal deposition in renal tubules and protected against deleterious effects of lithogenic treatment including weight loss, impaired renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted GSH and decreased antioxidant enzyme activities of the kidneys. In naïve rats, berberine (10mg/kg) increased urine volume and pH and decreased Ca(2+) excretion. Results of this study suggest the presence of antiurolithic effects in berberine against calcium oxalate stones mediated through a combination of antioxidant, diuretic, urinary alkalinizing and hypocalciuric effects. These data invite future studies on berberine to establish its efficacy for clinical use.
小檗碱是一种异喹啉生物碱，天然存在于几种具有肾结石病药用价值的植物中，是其主要成分。本研究旨在评估其抗结石形成的潜力，并探讨其潜在的作用机制。我们在体外检测了小檗碱的抗氧化作用，在动物草酸钙结石模型中检测了其利尿和抗结石作用。小檗碱对铁-抗坏血酸诱导的大鼠肾匀浆脂质过氧化具有浓度依赖性（50-150μg/ml）的抗氧化作用，其效力略高于参考抗氧化剂丁羟甲苯。在 Wistar 大鼠中，小檗碱（5-20mg/kg）增加尿排量，同时增加 pH 值和 Na(+)和 K(+)排泄，减少 Ca(2+)排泄，与氢氯噻嗪相似。在雄性 Wistar 大鼠通过在饮用水中添加 0.75%乙二醇建立的草酸钙结石动物模型中，小檗碱（10mg/kg）预防并消除了肾小管中草酸钙晶体沉积，并保护免受结石形成治疗的有害影响，包括体重减轻、肾功能受损和氧化应激，表现为丙二醛和蛋白质羰基含量增加、GSH 耗竭和肾脏抗氧化酶活性降低。在未处理的大鼠中，小檗碱（10mg/kg）增加了尿量和 pH 值，减少了 Ca(2+)排泄。本研究结果表明，小檗碱具有抗草酸钙结石的作用，其机制可能是抗氧化、利尿、尿液碱化和低钙作用的结合。这些数据为未来研究小檗碱的临床应用效果提供了依据。
