Abstract
Oxidative stress and apoptosis play important roles in the pathogenesis of various degenerative diseases. Previous studies have shown that naringin can exert therapeutic effects in multiple degenerative diseases by resisting oxidative stress and inhibiting apoptosis. Although naringin is effective in treating degenerative disc disease, the underlying mechanism remains unclear. This study is aimed at investigating the effects of naringin on oxidative stress, apoptosis, and intervertebral disc degeneration (IVDD) induced by cyclic stretch and the underlying mechanisms in vitro and in vivo. Abnormal cyclic stretch was applied to rat annulus fibrosus cells, which were then treated with naringin, to observe the effects of naringin on apoptosis, oxidative stress, mitochondrial function, and the nuclear factor- (NF-) κB signaling pathway. Subsequently, a rat model of IVDD induced by dynamic and static imbalance was established to evaluate the effects of naringin on the degree of degeneration (using imaging and histology), apoptosis, and oxidative stress in the serum and the intervertebral disc. Naringin inhibited the cyclic stretch-induced apoptosis of annulus fibrosus cells, reduced oxidative stress, improved mitochondrial function, enhanced the antioxidant capacity, and suppressed the activation of the NF-κB signaling pathway. Additionally, it reduced the degree of IVDD (evaluated using magnetic resonance imaging) and the level of oxidative stress and inhibited apoptosis and p-P65 expression in the intervertebral discs of rats. Thus, naringin can inhibit cyclic stretch-induced apoptosis and delay IVDD, and the underlying mechanism may be related to the inhibition of oxidative stress and activation of the NF-κB signaling pathway. Naringin may be an effective drug for treating degenerative disc disease.
Highlights
Intervertebral disc degeneration- (IVDD-) related diseases can significantly affect the mobility and quality of life of patients, thereby imposing a burden on the individual as well as the society [1, 2]
We previously found that the mitochondrial and endoplasmic reticulum-mediated pathways of apoptosis are involved in rat annulus fibrosus (AF) cell apoptosis induced by cyclic stretch; apoptosis could not be completely
Our results indicate that cyclic stretch-induced oxidative stress in AF cells could be inhibited by naringin
Summary
Intervertebral disc degeneration- (IVDD-) related diseases can significantly affect the mobility and quality of life of patients, thereby imposing a burden on the individual as well as the society [1, 2]. The etiology of IVDD is complex and multifactorial, and its molecular mechanism is currently unclear. We previously found that the mitochondrial and endoplasmic reticulum-mediated pathways of apoptosis are involved in rat annulus fibrosus (AF) cell apoptosis induced by cyclic stretch; apoptosis could not be completely. Oxidative Medicine and Cellular Longevity prevented by inhibiting these two pathways [5, 6]. This indicated the complexity of the mechanism underlying the cyclic stretch-induced apoptosis of intervertebral disc cells
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