Kim Jun, Choung Se-Young
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, Korea.
Mol Vis. 2017 Sep 11;23:638-648. eCollection 2017.
Rat pups treated with sodium selenite are typically used as an in vivo model to mimic age-related nuclear cataract. Reactive oxygen species (ROS) production, lipid peroxidation, reduction of antioxidant enzymes, crystalline proteolysis, and apoptosis are considered factors that contribute to pathogenesis of age-related nuclear cataract. In the present study, we investigated whether bark extract has potential to prevent cataract formation and elucidated the underlying mechanism.
Sprague Dawley rats were divided into six groups (n=10). Group 1 rat pups (the control) were treated with only normal saline. The rat pups in groups 2 to 6 were given a subcutaneous injection with sodium selenite (18 μmol/kg bodyweight) on postnatal (P) day 10. Group 3 rat pups (the positive control) were given gastric intubation with curcumin (80 mg/kg bodyweight) on P9, P10, and P11. The rat pups in groups 4 to 6 were given gastric intubation with bark extract 40 mg/kg, 80 mg/kg, and 120 mg/kg, respectively, on P9, P10, and P11.
This study showed that bark extract dose-dependently prevented cataract formation. Water-soluble protein, glutathione, superoxide dismutase, glutathione peroxidase, and catalase activity levels were found to be high, and conversely, water-insoluble protein, malondialdehyde, and Ca-ATPase were found to be low in the groups treated with bark extract compared to group 2. Real-time PCR analysis showed αA-crystalline, lens-specific m-calpain (), lens-specific intermediates (filensin and phakinin), and antiapoptotic factor () were downregulated, and the apoptotic factors (caspase-3 and Bax) and plasma membrane Ca-ATPase () were upregulated in group 2 compared to group 1. P. densiflora bark extract regulated the imbalance of these genes. The increased cleavage form of caspase-3 was lowered in the groups treated with bark extract. In conclusion, bark extract prevented selenite-induced cataract formation via regulating antioxidant enzymes, inhibiting -calpain-induced proteolysis, and apoptosis, and thus, maintained the transparency of the lens.
These results suggested that bark extract could be a new agent for preventing age-related nuclear cataract.
用亚硒酸钠处理的幼鼠通常被用作体内模型来模拟年龄相关性核性白内障。活性氧（ROS）生成、脂质过氧化、抗氧化酶减少、晶状体蛋白水解和细胞凋亡被认为是导致年龄相关性核性白内障发病的因素。在本研究中，我们调查了树皮提取物是否有预防白内障形成的潜力，并阐明了其潜在机制。
将Sprague Dawley大鼠分为六组（n = 10）。第1组幼鼠（对照组）仅用生理盐水处理。第2至6组幼鼠在出生后（P）第10天皮下注射亚硒酸钠（18 μmol/kg体重）。第3组幼鼠（阳性对照组）在P9、P10和P11经胃插管给予姜黄素（80 mg/kg体重）。第4至6组幼鼠在P9、P10和P11分别经胃插管给予40 mg/kg、80 mg/kg和120 mg/kg的树皮提取物。
本研究表明，树皮提取物呈剂量依赖性地预防白内障形成。与第2组相比，在接受树皮提取物处理的组中，发现水溶性蛋白、谷胱甘肽、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶活性水平较高，相反，水不溶性蛋白、丙二醛和钙 - ATP酶较低。实时PCR分析表明，与第1组相比，第2组中αA - 晶状体蛋白、晶状体特异性m - 钙蛋白酶（）、晶状体特异性中间产物（丝状晶状体蛋白和晶状体蛋白）和抗凋亡因子（）下调，而凋亡因子（半胱天冬酶 - 3和Bax）和质膜钙 - ATP酶（）上调。日本花柏树皮提取物调节了这些基因的失衡。在接受树皮提取物处理的组中，半胱天冬酶 - 3增加的裂解形式降低。总之，树皮提取物通过调节抗氧化酶、抑制 - 钙蛋白酶诱导的蛋白水解和细胞凋亡来预防亚硒酸钠诱导的白内障形成，从而维持晶状体的透明度。
这些结果表明，树皮提取物可能是预防年龄相关性核性白内障的一种新药。
