Neuroprotective properties of ethanolic extract of Citrus unshiu Markovich peel through NADPH oxidase 2 inhibition in chemotherapy-induced neuropathic pain animal model.

The present study aimed to determine the antioxidant effect of Citrus unshiu Markovich (CUM) extract in neuronal cell lines under oxidative stress and to investigate the effect of chemotherapy-induced peripheral neuropathy (CIPN) on the nociceptive response in a preclinical mice model. We tested the inhibition of H2 O2 in Neuro2A cells treated with CUM. Experimental animals were treated with oxaliplatin to induce CINP, and then administered oral CUM for 4 weeks in order to observe the effect of CUM. Animals were evaluated weekly for thermal hyperalgesia and digital motor nerve conduction velocity (NCV). Lumbar dorsal root ganglia (DRG) isolated from each animal were evaluated through immunochemical and western blot analysis for nerve damage, inflammatory response, and expression of redox signaling factors. The main mechanisms were determined to be decreased inducible nitric oxide synthase (iNOS) production due to the inhibition of NADPH oxidase 2 (NOX2). To determine the functional role of NOX2 in CINP, we administrated CUM into NOX2-deficient mice with neuropathic pain. Therefore, we suggest that CUM controls the expression levels of inflammatory factors in CINP via NOX2 inactivation. This study demonstrated that a complementary medicine such as CUM might be a potential novel therapeutic agent for the treatment of CINP.

Neuroprotective Effect of Nypa fruticans Wurmb by Suppressing TRPV1 Following Sciatic Nerve Crush Injury in a Rat.

Peripheral nerve injury can result in severe functional impairment and decreased quality of life due to loss of sensory and motor function. Nypa fruticans wurmb (NF) has been used in diverse folk remedies in East Asia. We have previously shown that Nypa fruticans wurmb extract has antinociceptive and anti-inflammatory effects by suppressing TRPV1 in the sciatic nerve injury. The present study investigated the effects of NF on the control of TRPV1 in relation to neuroprotective effects of a sciatic nerve crush injury. To evaluate the neuroprotective effects, an animal behavior test and a physiological function test were performed. Functional recovery and nerve recovery were improved in the NF and NF + SB (SB366791; TRPV1 antagonist) treated group. In the histomorphology evaluation, the neuronal regenerative effect of NF on the injured sciatic nerve was confirmed via hematoxylin and eosin (H&E) staining. In this study, the NF and NF + SB treated group showed neuroprotective and functional recovery effects from the sciatic nerve crush injury. Furthermore, the expression of NF-κB and iNOS showed a significantly suppressive effect on NF (p < 0.01), SB (p < 0.01), and NF + SB (p < 0.01) treated group at the 7th and 14th day compared to the vehicle group. This study confirmed the neuroprotective effects of NF on suppressing TRPV1 in a sciatic nerve crush injury. The findings of this study establish the effect of NF as a neurotherapeutic agent to protect the peripheral nerve after a sciatic nerve crush injury.