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. 2018 Jun;15(6):4987-4994.
doi: 10.3892/etm.2018.6072. Epub 2018 Apr 16.

Thymoquinone reduces spinal cord injury by inhibiting inflammatory response, oxidative stress and apoptosis via PPAR-γ and PI3K/Akt pathways

Yinming Chen  1 , Benlong Wang  1 , Hai Zhao  1
Affiliations

Thymoquinone reduces spinal cord injury by inhibiting inflammatory response, oxidative stress and apoptosis via PPAR-γ and PI3K/Akt pathways

Yinming Chen et al. Exp Ther Med. 2018 Jun.

Abstract

The present study used a mild contusion injury in rat spinal cord to determine that thymoquinone reduces inflammatory response, oxidative stress and apoptosis in a spinal cord injury (SCI) rat model and to demonstrate its possible molecular mechanisms. The rats in the thymoquinone group received 30 mg/kg thymoquinone once daily by intragastric administration from 3 weeks after surgery. Hematoxylin and eosin staining, Basso, Beattie and Bresnahan (BBB) scale and tissue water content detection were used in the present study to analyze the effect of thymoquinone on SCI. The activity of inflammatory response mediators, oxidative stress factors and caspase-3/9 was measured using ELISA kits. Furthermore, western blotting was performed to analyzed the protein expression levels of prostaglandin E2, suppressed cyclooxygenase-2 (COX-2) and activated peroxisome proliferator-activated receptor γ (PPAR-γ), PI3K and Akt. The results from the study demonstrated that thymoquinone increased Basso, Beattie and Bresnahan score and decreased water content in spinal cord tissue. Treatment with thymoquinone decreased inflammatory response [measured by levels of tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-18], oxidative stress (measured by levels of superoxide dismutase, catalase, glutathione and malondialdehyde) and cell apoptosis (measured by levels of caspase-3 and caspase-9) in SCI rats. Thymoquinone treatment inhibited prostaglandin E2 activity, suppressed COX-2 protein expression and activated PPAR-γ, PI3K and p-Akt protein expression in SCI rats. These data revealed that thymoquinone reduces inflammatory response, oxidative stress and apoptosis via PPAR-γ and PI3K/Akt pathways in an SCI rat model.

Keywords: peroxisome proliferator-activated receptor γ; phosphoinositide 3-kinase/Akt; spinal cord injury; thymoquinone.

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Figures

Figure 1.
Figure 1.
Structural formula of thymoquinone.
Figure 2.
Figure 2.
Effect of thymoquinone on SCI. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group.
Figure 3.
Figure 3.
Effect of thymoquinone on (A) BBB score and (B) water content in spinal cord tissue. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group; BBB, Basso, Beattie and Bresnahan.
Figure 4.
Figure 4.
Effect of thymoquinoneon inflammatory responses in SCI rats. Activity levels of (A) TNF-α, (B) IL-1β, (C) IL-6 and (D) IL-18 were measured using ELISA kits. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group; TNF, tumor necrosis factor; IL, interleukin.
Figure 5.
Figure 5.
Effect of thymoquinone on oxidative stress in SCI rats. Activity levels of (A) SOD, (B) CAT, (C) GSH and (D) MDA were measured using ELISA kits. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; MDA, malondialdehyde.
Figure 6.
Figure 6.
Effect of thymoquinone on cell apoptosis in SCI rats. Activity levels of (A) caspase-3 and (B) caspase-9 were measured using ELISA kits. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery + exercise group; Thymoquinone, SCI + thymoquinone group.
Figure 7.
Figure 7.
Effect of thymoquinone on PGE2 activity in SCI rats. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group; PGE2, prostaglandin E2.
Figure 8.
Figure 8.
Effect of thymoquinoneon COX-2 and PPAR-γ protein expressionin SCI rats. (A) COX-2 and (B) PPAR-γ protein expression were analyzed by (C) western blotting in SCI rats. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group; COX, cyclooxygenase; PPAR, peroxisome proliferator-activated receptor.
Figure 9.
Figure 9.
Effect of thymoquinone on PI3K/Akt protein expression in SCI rats. (A and B) Relative PI3K and p-Akt/Akt protein expression was analyzed by (C) western blotting in SCI rats. ##P<0.01 vs. Sham; **P<0.01 vs. Model. SCI, spinal cord injury; Sham, sham surgery group; Model, SCI surgery group; Thymoquinone, SCI + thymoquinone group; PI3K, phosphoinositide 3-kinase.
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