Effect of rutin on spinal cord injury through inhibition of the expression of MIP-2 and activation of MMP-9, and downregulation of Akt phosphorylation

Abstract

Rutin has extensive pharmacological activities, including antibacterial and anti-inflammatory activities, cooling of the blood to inhibit bleeding, reducing capillary wall fragility and anti-influenza activities. However, whether rutin can ameliorate neuropathic function in spinal cord injury (SCI) in constriction-induced peripheral nerve injury remains to be elucidated. In the present study, the potential protective effects of rutin on SCI rats were investigated. Neurological function was examined using the Basso, Beattie and Bresnahan (BBB) scoring system and by measuring the water content of the spinal cord tissue in SCI rats. SCI-induced programmed cell death was measured using hematoxylin and eosin staining. In addition, the expression of macrophage inflammatory protein-2 (MIP-2) and the activation of matrix metalloproteinase-9 (MMP-9) in the SCI rats were evaluated using ELISA assay kits and zymographic analysis, respectively. The phosphorylation of protein kinase B (p-Akt) was analyzed using a western blot assay. The results demonstrated that administrating rutin began to increase BBB scores and attenuate the spinal cord water content of the SCI rats. Administrating rutin prevented SCI-induced programmed cell death. The SCI rats of in the rutin-treated group were found to exhibit lower expression levels of MIP-2 and p-Akt, reduced MMP-9 activation, compared with the SCI model rats. In conclusion, rutin was demonstrated as a potential protective agent in SCI and enhances the neurotrophic effect by inhibiting the expression of MIP-2 and activation of MMP-9, and downregulating the expression of p-Akt.

Gambogic acid inhibits spinal cord injury and inflammation through suppressing the p38 and Akt signaling pathways

“…Akt is activated by translocation to the inner surface of cell membranes and subsequent phosphorylation (7). Phosphatidylinositol 3-kinase (PI3K) is activated by the phosphorylation of the third hydroxyl group on its inositol ring, which further phosphorylates inositol in the cell membrane to translocate serine/threonine protein kinase (8). Previous studies have indicated that the activation of Akt protects nerves by inhibiting the apoptosis of nervous cells, reducing the generation of oxygen free radicals and suppressing the inflammatory reaction when SCI occurs (7,9).…”

Dendrobium officinale flos increases neurotrophic factor expression in the hippocampus of chronic unpredictable mild stress‐exposed mice and in astrocyte primary culture and potentiates NGF‐induced neuronal differentiation in PC12 cells

“…Among these chemicals, rutin, a flavonoid, alleviates depression‐like behaviours in animals via modulation of serotonergic and noradrenergic systems (Machado et al, 2008; Parashar, Mehta, & Udayabanu, 2017; Yusha'U et al, 2017). In addition, rutin also modulated neurotrophic factor systems in an animal model of Huntington's disease, as well as ischemia–reperfusion injury or beta‐amyloid‐induced neurotoxicity in rats (Abdelfattah et al, 2019; Moghbelinejad et al, 2014; Zhang & Ma, 2015). in vitro analysis showed that treatment of an immortalized mouse hippocampal neuronal cell line, HT22, with rutin could prevent ethanol‐induced toxicity by enhancing the expression of NGF, BDNF, and GDNF (Song, Na, Kim, & Kwon, 2015).…”

Therapeutic potential of flavonoids in spinal cord injury

“…Furthermore, rutin attenuated 6-hydroxydopamine-induced neurotoxicity via improving antioxidant enzyme levels and reducing lipid peroxidation in PC-12 cells (Magalingam, Radhakrishnan, and Haleagrahara, 2013). Moreover, in vivo, rutin has been demonstrated to enhance the neurotrophic effect by reduction of macrophage inflammatory protein-2 (MIP-2) and p-Akt expression and matrix metallopeptidase-9activation in SCI rats (Zhang and Ma, 2015). Furthermore, rutin augments Basso Beattie Bresnahan scores and decreased spinal cord water content of SCI rats.…”

“…In addition, rutin can prevent SCI-induced programmed cell death in SCI rats model (Zhang and Ma, 2015). A study revealed that rutin reduced programmed cell death by influencing the down-regulation of the NLRP3 in an alcohol and cerulein-induced rat model of pancreatitis .…”