Curcumin Mitigates Neuropathic-induce Muscle Atrophy By Suppressing CaMK2/NF-kB Pathway

Neuropathy can induce inflammation that results in muscle atrophy. Curcumin has been shown to exert an anti-inflammatory effect, preserving muscle mass in diabetic rats. However, the mechanism of curcumin to preserve muscle mass in neuropathy is not known. PURPOSE: To examine the effect of curcumin on the intramuscular inflammation and muscle cross-sectional area (CSA) in a neuropathy rodent model. METHODS: Twelve rats were randomly assigned to three groups: sham (CON), spinal nerve ligation (SNL), and SNL + 100curcumin/Kg BW (100CUR). The right (R) lumbosacral section (i.e., L5/L6) of the spinal cord was ligated (SNL and 100CUR) or sham surgery (CON) was performed, whereas the contralateral side (left: L) was served as their own control. Rats were fed with a control diet without (i.e., CON and SNL) or with (i.e., 100CUR) curcumin supplementation for 4 weeks. Plantaris (left and right) and tibialis anterior (TA; right) muscles were collected. TA was stained for dystrophin to measure CSA. Left and right plantaris were analyzed for protein content for AChR, CaMK2, CaMK2Thr286, CaMK2Thr286/CaMK2, NF-κB, NF-κBSer536, NF-κBSer536/NF-κB, IL-1β, and GAPDH. Each protein was normalized to GAPDH then to the CON. RESULTS: A significant (p ≤ 0.05) group effect was observed for TA CSA and a group x leg interaction effect was observed for CaMK2Thr286/CaMK2, NF-κBSer536, IL-1β protein content. For muscle CSA, CON (9027.33 ± 603.39 μm2) and 100CUR (8853.68 ± 696.73 μm2) were larger than SNL (4771.01 ± 539.69 μm2). No difference was observed in CSA between CON and 100CUR. Additionally, when compared between left and right plantaris muscles, only SNL had greater CaMK2Thr286/CaMK2 (R: 2.63 ± 1.87 vs. L: 1.56 ± 1.65), NF-κBSer536 (R: 1.85 ± 0.83 vs. L: 0.55 ± 0.33), and IL-1β (R: 2.11 ± 1.32 vs. L: 0.65 ± 0.29) protein content in the right than the left leg, whereas, no difference was observed for left leg among groups. For NF-κBSer536, SNL (1.85 ± 0.83) was greater than 100CUR (0.91 ± 0.52) in the right leg. No significant differences were observed for AChR, CaMK2, CaMK2Thr286, and NF-κBSer536/NF-κB. CONCLUSION: In a neuropathic model, muscle atrophy was observed with concomitant increase in CaMK2/NF-κB/IL-1β activation in the ipsilateral plantaris. Curcumin supplementation appears to mitigate this inflammatory response and muscle mass loss.