Methoxytetrahydro‐2H‐pyran‐2‐yl)methyl benzoate inhibits spinal cord injury in the rat model via PPAR‐γ/PI3K/p‐Akt activation

Abstract

Spinal cord injury (SCI) is the most commonly seen trauma leading to disability in people worldwide. The purpose of current study was to determine the protective effect of methoxytetrahydro-2H-pyran-2-yl)methyl benzoate (HMPB) on SCI in rat model. TUNEL staining was used to examine apoptotic changes in spinal cord of SCI rats. The ELISA kits were employed to assess inflammatory processes and oxidative factors in the spinal cord tissues. Behavioral changes in SCI rats were assessed using Basso, Beattie, and Bresnahan (BBB) scoring system. Western blotting was used for assessment of proteins. The HMPB treatment of SCI rats reduced apoptotic cell number based on the concentration of dose administered. Treatment of SCI rats with HMPB enhanced BBB score and decreased accumulation of water content in SCI rats significantly. On treatment with HMPB the TNF-α and interleukin-6/1β/18 levels were suppressed in SCI rats. Treatment with HMPB induced excessive release of SOD, CAT, and GSH molecules and decreased overproduction of MDA. The SCI induced upregulation of caspase-3/9 activity was completely alleviated by HMPB at 2 mg/kg dose. The HMPB treatment of SCI rats promoted peroxisome proliferator-activated receptor γ (PPAR-γ) expression, reduced cyclooxygenase (COX)-2 production and increased expression of p-Akt and phosphoinositide 3-kinase (p-PI3K). The study demonstrated that HMPB suppressed apoptosis, raised BBB score and inhibited inflammation in SCI rats. Moreover, activation of PI3K/Akt in the spinal cord tissues of SCI rats was promoted by HMPB. Therefore, HMPB has protective effect on SCI in the rat model. K E Y W O R D S apoptosis, behavioral changes, edema, inflammation, spinal cord injury

Effect of Sirtuin-1 and Wnt/β-Catenin Signaling Pathway in Rat Model of Spinal Cord Injury

“…Spinal cord injury (SCI) is a serious neurological disorder characterized by complete or partial impairment of motor function leading to loss of motor function, which has caused chronic impairment and disability [ 1 , 2 ]. SCI contains primary and secondary injuries.…”

PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway

“…The antiinflammatory mechanism of PPARα is primarily associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of NF-κB. The previous studies have identified that PPARα plays crucial role and is widely involved in the progression of SCI [12][13][14]. Importantly, the endogenous fatty acid palmitoylethanolamide (PEA), as a PPARα agonist, is one of the members of N-acylethanolamines family [15].…”