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

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.

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

“…For example activities of caspases like caspase-3, caspase-9 or cleaved caspase -3 are studied as hall marks of apoptosis in cancer cells (Gupta et al, 2018a, Gupta et al, 2018b). Treatment of TQ in spinal cord injury reduces the activity of caspase-3 and caspase-9 and inhibited apoptosis in an animal model (Chen et al, 2018) and the same mechanism has also been reported in gastric carcinoma (Gali-Muhtasib et al, 2004).…”

Cistanches alleviates sevoflurane‐induced cognitive dysfunction by regulating PPAR‐γ‐dependent antioxidant and anti‐inflammatory in rats

“…41 The ability of PPAR-γ to exert anti-inflammatory effects has been extensively studied, [42][43][44] Moreover, activation of PPAR-γ exerts anti-inflammatory effects via inhibiting the transcription factors, such as activator protein-1 and nuclear factor-kB. 46 What' more, PPAR-γ is expressed in various cell types including astrocytes, microglia and neurons in the brain, and PPAR-γ activation in microglia leads to reduce the production of pro-inflammatory cytokines by these cells. 45 Chen et al demonstrated that thymoquinone inhibits spinal cord injury via preventing inflammatory response, apoptosis and oxidative stress through PPAR-γ and PI3K/Akt pathways.…”

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

“…Interestingly, in a parallel pathway, TQ has also been shown to induce the expression of pro-apoptotic proteins via PPAR-γ in breast cancer cell lines [92]. TQ has been reported to induce the expression of PPAR-γ in diverse cellular contexts [92,93]. In breast cancer cells, TQ-mediated activation of PPAR-γ leads to the downregulation of the expression of the pro-survival genes Bcl-2 and BCL-xL [92].…”