Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis

Abstract

Purpose To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms. Methods Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis. Results The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant. Conclusions FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

In Situ Cross-Linkable Hyaluronic–Ferulic Acid Conjugate Containing Bucladesine Nanoparticles Promotes Neural Regeneration after Spinal Cord Injury

“…Notably, compared to the other groups, there was a faster recovery of motor functions in the HSP-F/BCS group (Videos S1−S4). The improvement in functional recovery is comparable to previous studies, in which the effect of FA, 13,14 Buc 21 or HA-based hydrogel 43 was investigated separately in SCI repair. Although a trend in improved performance was reported in the HA-based hydrogel, it was not significant compared to the control.…”

“…Ferulic acid (FA) is a potent antioxidant, and its phenolic hydroxyl group can protect cells from oxidative stress. It could reduce the inflammatory responses induced by microglia. , It has been shown that FA could protect neurons after cerebral ischemic injury with anti-inflammatory and antioxidative effects . Yabe et al indicated that FA increases the proliferation of neural stem/progenitor cells (NSCs/NPCs) in vitro and in vivo , and improves stress-induced depressive behavior in mice .…”

“…The main objective of this study was to prepare a multifunctional bioactive hydrogel with desirable physicochemical properties, reducing glial scar, as the main obstacle of axon repair, and preventing secondary damage by inhibiting oxidative stress. Although few studies have been reported on the neuroprotective function of FA, ,, to the best of our knowledge, its application in the lesion site, especially in the intermediate phase of SCI, has not been studied so far. The conjugates could provide synergistic and multitarget action .…”

Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis

“…Therefore, we aim to further screen and develop candidate bioactive ingredient in the potential application against COVID-19 and ICH. Ferulic acid, a neuroprotective phytochemical, has exerted anti-inflammatory activity for protective action against nerve injury ( Jiang et al, 2021 ). In pharmacokinetic analysis in vivo using ultra-high performance liquid chromatography approach, the data show that the peak concentration of ferulic acid is 27.50 min under 0.199 mg/L.…”

Involvement of NLRP3 inflammasome pathway in the protective mechanisms of ferulic acid and p-coumaric acid in LPS-induced sickness behavior and neuroinflammation in mice

“…Like other polyphenolic compounds, the antioxidant properties of FA have been extensively reported (Graf 1992 ; Zduńska et al 2018 ). Moreover, FA has been observed to be effective in depression (Singh et al 2017 ; Liu et al 2017 ; Zeni et al 2017 ; Zheng et al 2019 ), neuroinflammation (Sun et al 2021 ; Jiang et al 2021 ; Singh 2017; Rehman et al 2019 ), neurodegeneration (Chaudhary et al 2019 ; Singh et al 2017 ; Sultana 2012 ), and cancer (Zduńska et al 2018 ). FA inhibits NF-κB, iNOS, COX-2 and modulates LPS-induced TLR4 pathway (Rehman et al 2019 ; Jung et al 2009 ).…”