Xu Xian-Xiang, Zhang Xiao-Hong, Diao Yong, Huang Yu-Xiang
Department of Pharmacy, Huaqiao University, Quanzhou, China.
Department of Pharmacy, Huaqiao University, Quanzhou, China.
Kaohsiung J Med Sci. 2017 Feb;33(2):62-68. doi: 10.1016/j.kjms.2016.11.004. Epub 2016 Dec 30.
Achyranthes bidentate Blume (Niuxi) is often employed for treatment of arthritis in Traditional Chinese Medicine and possesses anti-inflammatory properties. Phytochemical and pharmacological studies proved the oleanane-type saponins to be the main bioactive principles. In the present study, protective effects of A. bidentata saponins (ABS) on inflammation and apoptosis in interleukine-1β (IL-1β)-induced chondrocytes were investigated. Rat chondrocytes were pretreated with ABS at 3 μg/mL, 10 μg/mL, and 30 μg/mL, and subsequently stimulated with IL-1β (10 ng/mL). Methylthiazolyldiphenyl-tetrazolium bromide assay and annexin V/propidium iodide dual staining demonstrated that ABS could protect IL-1β-induced chondrocyte injury. ABS suppressed IL-1β-induced apoptosis by suppressing the activation of caspase-3, inhibiting levels of proapoptotic proteins Bax and Bad, decreasing p53 protein phosphorylation, and promoting the expression of antiapoptotic protein Bcl-x and proliferating cell nuclear antigen. IL-1β-induced inflammation and matrix degradation were also alleviated by ABS through the downregulation of the expressions of matrix metalloproteinases 3 and 9 and cyclooxygenase-2. Moreover, ABS inhibited IL-1β-induced nuclear factor κB activation in rat chondrocytes. We demonstrated, for the first time, the protective effects of ABS on IL-1β-stimulated chondrocytes and their molecular mechanisms. Thus, it is suggested that ABS might be a potential drug in the treatment of osteoarthritis.
牛膝在传统中医中常用于治疗关节炎,具有抗炎特性。植物化学和药理学研究证明齐墩果烷型皂苷是其主要生物活性成分。在本研究中,考察了牛膝皂苷(ABS)对白细胞介素-1β(IL-1β)诱导的软骨细胞炎症和凋亡的保护作用。将大鼠软骨细胞分别用3μg/mL、10μg/mL和30μg/mL的ABS预处理,随后用IL-1β(10ng/mL)刺激。甲基噻唑基二苯基溴化四氮唑法和膜联蛋白V/碘化丙啶双染法表明,ABS可保护IL-1β诱导的软骨细胞损伤。ABS通过抑制半胱天冬酶-3的激活、抑制促凋亡蛋白Bax和Bad的水平、降低p53蛋白磷酸化以及促进抗凋亡蛋白Bcl-x和增殖细胞核抗原的表达来抑制IL-1β诱导的凋亡。ABS还通过下调基质金属蛋白酶3和9以及环氧化酶-2的表达减轻IL-1β诱导的炎症和基质降解。此外,ABS抑制IL-1β诱导的大鼠软骨细胞核因子κB激活。我们首次证明了ABS对IL-1β刺激的软骨细胞的保护作用及其分子机制。因此,提示ABS可能是治疗骨关节炎的一种潜在药物。