School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Am J Chin Med. 2012;40(3):551-66. doi: 10.1142/S0192415X12500425.
Schisandrin B (Sch B) is an active ingredient of the fruit of Schisandra chinensis. It has many therapeutic effects arising from its tonic, sedative, antitussive and antiaging activities and is also used in the treatment of viral and chemical hepatitis. The aim of this study was to investigate the protective effects of Sch B on cyclosporine A (CsA)-induced nephrotoxicity in mice and HK-2 cells (a human proximal tubular epithelial cell line). After gavage with Sch B (20 mg/kg) or olive oil (vehicle), mice received CsA (30 mg/kg) by subcutaneous injection once daily for four weeks. Renal function, histopathology, and tissue glutathione (GSH) and malondialdehyde (MDA) levels were evaluated after the last treatment. The effects of Sch B on CsA-induced oxidative damage in HK-2 cells were investigated by measuring cell viability, the release of lactate dehydrogenase (LDH), the level of reactive oxygen species (ROS), and the cellular GSH and ATP concentrations. Cellular apoptosis was assessed by flow cytometry. Treatment with Sch B in CsA-treated mice significantly suppressed the elevation of blood urea nitrogen (BUN) and serum creatinine levels and attenuated the histopathological changes. Additionally, Sch B also decreased renal MDA levels and increased GSH levels in CsA-treated mice. Using an in vitro model, Sch B (2.5, 5 and 10 μM) significantly increased the cell viability and reduced LDH release and apoptosis induced by CsA (10 μM) in HK-2 cells. Furthermore, Sch B increased the intracellular GSH and ATP levels and attenuated CsA-induced ROS generation. In conclusion, Sch B appears to protect against CsA-induced nephrotoxicity by decreasing oxidative stress and cell death.
五味子醇 B（Sch B）是五味子果实的一种活性成分。它具有滋补、镇静、止咳和抗衰老等多种治疗作用，也用于治疗病毒性和化学性肝炎。本研究旨在探讨五味子醇 B 对环孢素 A（CsA）诱导的小鼠肾毒性和 HK-2 细胞（人近端肾小管上皮细胞系）的保护作用。灌胃给予五味子醇 B（20mg/kg）或橄榄油（载体）后，小鼠每天通过皮下注射 CsA（30mg/kg）一次，连续四周。末次给药后评估肾功能、组织学、组织谷胱甘肽（GSH）和丙二醛（MDA）水平。通过测量细胞活力、乳酸脱氢酶（LDH）释放、活性氧（ROS）水平以及细胞内 GSH 和 ATP 浓度，研究五味子醇 B 对 CsA 诱导的 HK-2 细胞氧化损伤的影响。通过流式细胞术评估细胞凋亡。在 CsA 处理的小鼠中，给予五味子醇 B 治疗可显著抑制血尿素氮（BUN）和血清肌酐水平的升高，并减轻组织病理学变化。此外，五味子醇 B 还降低了 CsA 处理小鼠肾脏的 MDA 水平并增加了 GSH 水平。在体外模型中，五味子醇 B（2.5、5 和 10μM）显著增加了细胞活力，降低了 CsA（10μM）诱导的 HK-2 细胞的 LDH 释放和凋亡。此外，五味子醇 B 增加了细胞内 GSH 和 ATP 水平，并减轻了 CsA 诱导的 ROS 生成。总之，五味子醇 B 通过降低氧化应激和细胞死亡来防止 CsA 诱导的肾毒性。
