Curcumin Mitigates Muscle Atrophy Potentially by Attenuating Calcium Signaling and Inflammation in a Spinal Nerve Ligation Model

Denervation-induced calcium/calmodulin-dependent protein kinase II (CaMKII) activation and inflammation can result in muscle atrophy. Curcumin and bisdemethoxycurcumin are well known to exhibit an anti-inflammatory effect. In addition, curcumin has been shown to attenuate CaMKII activation in neuron...

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Main Authors: Casey Appell, Nigel C. Jiwan, Chwan-Li Shen, Hui-Ying Luk
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/46/11/742
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Summary:Denervation-induced calcium/calmodulin-dependent protein kinase II (CaMKII) activation and inflammation can result in muscle atrophy. Curcumin and bisdemethoxycurcumin are well known to exhibit an anti-inflammatory effect. In addition, curcumin has been shown to attenuate CaMKII activation in neuronal cells. This study aimed to examine the effect of curcumin or bisdemethoxycurcumin on CaMKII activation, inflammation, and muscle cross-sectional area (CSA) in spinal nerve ligated rats. Sixteen female rats were assigned to sham (CON), spinal nerve ligation (SNL), SNL+ curcumin 100 mg/kg BW (100CUR), and SNL+ bisdemethoxycurcumin 50 mg/kg BW (50CMO) for 4 weeks. Ipsilateral (surgical) soleus and tibialis anterior (TA) muscles was stained for dystrophin to measure CSA. Ipsilateral and contralateral (non-surgical) plantaris muscles were analyzed for protein content for acetylcholine receptor (AChR), CaMKII, CaMKII<sup>Thr286</sup>, nuclear factor-κB (NF-κB), NF-κB<sup>Ser536</sup>, and interleukin-1β (IL-1β) and normalized to α-tubulin and then CON. A significant (<i>p</i> < 0.050) group effect was observed for TA CSA where CON (11,082.25 ± 1617.68 μm<sup>2</sup>; <i>p</i> < 0.001) and 100CUR (9931.04 ± 2060.87 μm<sup>2</sup>; <i>p</i> = 0.018) were larger than SNL (4062.25 ± 151.86 μm<sup>2</sup>). In the ipsilateral plantaris, the SNL (4.49 ± 0.69) group had greater CaMKII activation compared to CON (1.00 ± 0.25; <i>p</i> = 0.010), 100CUR (1.12 ± 0.45; <i>p</i> = 0.017), and 50CMO (0.78 ± 0.19; <i>p</i> = 0.009). The ipsilateral plantaris (2.11 ± 0.66) had greater IL-1β protein content than the contralateral leg (0.65 ± 0.14; <i>p</i> = 0.041) in the SNL group. In plantaris, the SNL (1.65 ± 0.51) group had greater NF-κB activation compared to CON (1.00 ± 0.29; <i>p</i> = 0.021), 100CUR (0.61 ± 0.10; <i>p</i> = 0.003), 50CMO (0.77 ± 0.25; <i>p</i> = 0.009) groups. The observed reduction in Ca<sup>2+</sup> signaling and inflammation in type II plantaris muscle fibers might reflect the changes within the type II TA muscle fibers which may contribute to the mitigation of TA mass loss with curcumin supplementation.
ISSN:1467-3037
1467-3045