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Scientific Reports
Nature - Research
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Abstract: |
We have previously demonstrated that the Thymus algeriensis and Thymus fontanesii extracts have
powerful anti-inflammatory, antipyretic, and analgesic effects against acute pain models. We profiled
their chemical composition and found many phenolic acids, flavonoids, and phenolic diterpenes.
In this work, we investigated their antioxidant properties on HaCaT cells exposed to UVA-induced
oxidative stress and examined their effects against chronic neuropathic pain and the underlying
mechanisms. Through a rat chronic constriction injury (CCI) model, we induced chronic neuropathic
pain by placing 4 loose ligatures around the right sciatic nerve for 14 days. Thermal and mechanical
hyperalgesia in addition to cold and dynamic allodynia were tested on the day before surgery and on
the 7th and 14th post-surgery days. Key markers of the nitrosative and oxidative stresses, in addition
to markers of inflammation, were measured at day 14 post surgery. Histopathological examination
and immunostaining of both synaptophysin and caspase-3 of sciatic nerve and brain stem were also
performed. Results of this study showed that T. algeriensis extract suppresses UVA oxidative stress in
HaCaT cells via activation of the Nrf-2 pathway. Both extracts attenuated hyperalgesia and allodynia
at 7- and 14-days post-surgery with more prominent effects at day 14 of surgery. Their protective
effects against neuropathic pain were mediated by inhibiting NOX-1, iNOS, by increasing the enzyme
activity of catalase, and inhibition of inflammatory mediators, NF-κB, TNF-α, lipoxygenase, COX-2
enzymes, and PGE2. Furthermore, they improved deleterious structural changes of the brainstem and
sciatic nerve. They also attenuated the increased caspase-3 and synaptophysin. The data indicate that
both extracts have neuroprotective effects against chronic constriction injury-induced neuropathic
pain. The observed protective effects are partially mediated through attenuation of oxidative and
nitrosative stress and suppression of both neuroinflammation and neuronal apoptosis, suggesting
substantial activities of both extracts in amelioration of painful peripheral neuropathy.
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