Int J Med Sci 2021; 18(12):2480-2492. doi:10.7150/ijms.59169

Research Paper

Inhibition of Lipopolysaccharide-Induced Inflammatory and Oxidative Responses by Trans-cinnamaldehyde in C2C12 Myoblasts

Cheol Park1, Hyesook Lee2,3, Suhyun Hong2,3, Ilandarage Menu Neelaka Molagoda4, Jin-Woo Jeong5, Cheng-Yun Jin6, Gi-Young Kim4, Sung Hyun Choi7, Sang Hoon Hong8, Yung Hyun Choi2,3✉

1. Division of Basic Sciences, College of Liberal Studies, Dong-Eui University, Busan 47340, Republic of Korea.
2. Anti-Aging Research Center, Dong-eui University, Busan 47340, Republic of Korea.
3. Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Republic of Korea.
4. Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, Republic of Korea.
5. Nakdonggang National Institute of Biological Resources, Sangju 37242, Republic of Korea.
6. School of Pharmaceutical Sciences, Zhengzhou University, Henan 450001, China.
7. Department of System Management, Korea Lift College, Geochang 50141, Republic of Korea.
8. Department of Internal Medicine, Dong-eui University College of Korean Medicine, Busan 47227, Republic of Korea.

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Citation:
Park C, Lee H, Hong S, Molagoda IMN, Jeong JW, Jin CY, Kim GY, Choi SH, Hong SH, Choi YH. Inhibition of Lipopolysaccharide-Induced Inflammatory and Oxidative Responses by Trans-cinnamaldehyde in C2C12 Myoblasts. Int J Med Sci 2021; 18(12):2480-2492. doi:10.7150/ijms.59169. Available from https://www.medsci.org/v18p2480.htm

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Abstract

Background: Trans-cinnamaldehyde (tCA), a bioactive component found in Cinnamomum cassia, has been reported to exhibit anti-inflammatory and antioxidant effects, but its efficacy in muscle cells has yet to be found. In this study, we investigated the inhibitory effect of tCA on inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in C2C12 mouse skeletal myoblasts.

Methods: To investigate the anti-inflammatory and antioxidant effects of tCA in LPS-treated C2C12 cells, we measured the levels of pro-inflammatory mediator, cytokines, and reactive oxygen species (ROS). To elucidate the mechanism underlying the effect of tCA, the expression of genes involved in the expression of inflammatory and oxidative regulators was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of tCA against LPS in the zebrafish model.

Results: tCA significantly inhibited the LPS-induced release of pro-inflammatory mediators and cytokines, which was associated with decreased expression of their regulatory genes. tCA also suppressed the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor, and attenuated the nuclear translocation of nuclear factor-kappa B (NF-κB) and the binding of LPS to TLR4 on the cell surface in LPS-treated C2C12 cells. Furthermore, tCA abolished LPS-induced generation of ROS and expression levels of ROS producing enzymes, NADPH oxidase 1 (NOX1) and NOX2. However, tCA enhanced the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in LPS-stimulated C2C12 myoblasts. In addition, tCA showed strong protective effects against NO and ROS production in LPS-injected zebrafish larvae.

Conclusions: Our findings suggest that tCA exerts its inhibitory ability against LPS-induced inflammatory and antioxidant stress in C2C12 myoblasts by targeting the TLR4/NF-κB, which might be mediated by the NOXs and Nrf2/HO-1 pathways.

Keywords: Trans-cinnamaldehyde, inflammation, oxidative stress, TLR4/NF-κB, Nrf2/HO-1.