Ding Guoliang, Zhao Jianquan, Jiang Dianming
Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Exp Ther Med. 2016 Jun;11(6):2553-2560. doi: 10.3892/etm.2016.3179. Epub 2016 Mar 23.
Osteoporosis is a disease of the skeleton that is characterized by the loss of bone mass and degeneration of bone microstructure, resulting in an increased risk of fracture. Oxidative stress, which is known to promote oxidative damage to mitochondrial function and also cell apoptosis, has been recently indicated to be implicated in osteoporosis. However, there are few agents that counteract oxidative stress in osteoporosis. In the present study, the protective effects of allicin against the oxidative stress-induced mitochondrial dysfunction and apoptosis were investigated in murine osteoblast-like MC3T3-E1 cells. The results demonstrated that allicin counteracted the reduction of cell viability and induction of apoptosis caused by hydrogen peroxide (HO) exposure. The inhibition of apoptosis by allicin was confirmed by the inhibition of HO-induced cytochrome release and caspase-3 activation. Moreover, the inhibition of apoptosis by allicin was identified to be associated with the counteraction of HO-induced mitochondrial dysfunction. In addition, allicin was demonstrated to be able to significantly ameliorate the repressed phosphoinositide 3-kinase (PI3K)/AKT and cyclic adenosine monophosphate response element-binding protein (CREB)/extracellular-signal-regulated kinase (ERK) signaling pathways by HO, which may also be associated with the anti-oxidative stress effects of allicin. In conclusion, allicin protects osteoblasts from HO-induced oxidative stress and apoptosis in MC3T3-E1 cells by improving mitochondrial function and the activation of PI3K/AKT and CREB/ERK signaling. The present study implies a promising role of allicin in oxidative stress-associated osteoporosis.
骨质疏松症是一种骨骼疾病，其特征是骨量丢失和骨微结构退化，导致骨折风险增加。氧化应激已知会促进对线粒体功能的氧化损伤以及细胞凋亡，最近有研究表明其与骨质疏松症有关。然而，在骨质疏松症中，能够对抗氧化应激的药物很少。在本研究中，我们在小鼠成骨样MC3T3-E1细胞中研究了大蒜素对氧化应激诱导的线粒体功能障碍和细胞凋亡的保护作用。结果表明，大蒜素可对抗过氧化氢（HO）暴露引起的细胞活力降低和细胞凋亡诱导。大蒜素对细胞凋亡的抑制作用通过抑制HO诱导的细胞色素释放和半胱天冬酶-3激活得到证实。此外，大蒜素对细胞凋亡的抑制作用被确定与对抗HO诱导的线粒体功能障碍有关。此外，大蒜素被证明能够显著改善HO对磷酸肌醇3-激酶（PI3K）/AKT和环磷酸腺苷反应元件结合蛋白（CREB）/细胞外信号调节激酶（ERK）信号通路的抑制作用，这也可能与大蒜素的抗氧化应激作用有关。总之，大蒜素通过改善线粒体功能以及激活PI3K/AKT和CREB/ERK信号通路，保护成骨细胞免受HO诱导的氧化应激和MC3T3-E1细胞凋亡。本研究表明大蒜素在氧化应激相关的骨质疏松症中具有潜在的作用。
