Regulatory effect of curcumin on splenic inflammation in overtraining rats and its mechanism

doi:10.12047/j.cjap.6075.2021.022

Abstract

Abstract: Objective: To study the alleviating effects of curcumin on splenic inflammation in overtraining rats by regulating toll-like receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Methods: Male Wistar rats of 7-week old were divided into control group (C group, 12), overtraining model group (OM group, 11), curcumin + overtraining model group (COM group, 14). C Group did not undergo any exercise intervention. OM and COM group underwent 8-week incremental load swimming training. During the training, rats in the COM group were treated with 200 mg/ (kg·d) curcumin in the volume as 5 ml/kg, and the other groups were treated with an equal volume of 0.5 % sodium carboxymethylcellulose. 24 hours after the last training, the spleen index was calculated by weighing, the pathological changes of the spleen were observed by light microscopy, and the biochemical indicators of blood and spleen were detected. Results: After 8-week incremental load swimming training, the splenic structure in C group was normal under light microscope; the spleen index of OM group was significantly lower than that of C group (P＜0.01) and pathological changes of inflammation were obvious; the spleen index of COM group was significantly higher than that of OM group (P＜0.05) and pathological changes of inflammation were alleviated. Compared with C group, in OM group, the serum levels of corticosterone (Cor), NF-κB, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and TLR4 expression rate on splenic monocytes surface, splenic TNF-α, IL-6 were increased (P＜0.05 or P＜0.01), the expressions of p38 MAPK, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and NF-κB in spleen were increased (P＜0.05 or P＜ 0.01); serum testosterone (T), serum and splenic interleukin-10 (IL-10) were decreased (P＜0.01). Compared with OM group, in COM group, serum levels of Cor, NF-κB, TNF-α, IL-6 and TLR4 expression rate on splenic monocytes surface, splenic TNF-α, IL-6 were decreased (P＜0.05 or P＜0.01), the expressions of p38 MAPK, p-p38 MAPK and NF-κB in spleen were decreased (P＜ 0.05); serum T, serum and splenic IL-10 were increased (P＜0.05). The trend of T/Cor ratio between groups was consistent with testosterone change. Conclusion: The 8-week incremental load swimming training aggravated inflammation of spleen in rats, led to pathological inflammatory changes. Curcumin supplementation during training can down-regulate expressions of TLR4-p38 MAPK/NF-κB signaling pathway-related proteins, thereby maintaining a dynamic equilibrium between pro-inflammatory/anti-inflammatory cytokines, protecting the spleen.

Key words: curcumin, overtraining, inflammation, rat, spleen

CLC Number:

G804.7

WANG Pin, CAO Jian-min, HU Ge, ZHOU Hai-tao, ZHANG Jing, GUO Xian, NIU Yan-long, CHENG Xin-yun, LI Jia-bei. Regulatory effect of curcumin on splenic inflammation in overtraining rats and its mechanism[J]. CJAP, 2021, 37(3): 281-286.

References 21

[1]	Chen JQ,Szodoray P,Zeher M. Toll-like receptor pathways in autoimmune diseases[J]. Clin Rev Allergy Immunol, 2016, 50(1): 1-17.
[2]	Hamerman JA, Pottle J, Ni M, et al. Negative regulation of TLR signaling in myeloid cells--implications for autoimmune diseases[J]. Immunol Rev, 2016, 269(1): 212-227.
[3]	周新. 大球盖菇多糖对过度运动大鼠脾脏免疫机能及p-p38MAPK蛋白表达的影响[J]. 扬州大学学报(农业与生命科学版), 2019, 40(6): 71-75.
[4]	Yuan X, Xu S, Huang H, et al. Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model[J]. Scand J Med Sci Sport, 2018, 28(5): 1541-1551
[5]	Xu XY, Meng X, Li S, et al. Bioactivity, health benefits, and related molecular mechanisms of curcumin: current progress, challenges, and perspectives[J]. Nutrients, 2018, 10(10): 1553.
[6]	周海涛, 曹建民, 米生权, 等. 姜黄素对运动性肾缺血再灌注损伤大鼠肾组织中炎症因子蛋白及基因表达的影响[J]. 天然产物研究与开发, 2018, 30(10): 1687-1694.
[7]	Wang J, Cao JM, Huang AL, et al. Effect of haematococcus pluvialis on exercise-related renal ischemia-reperfusion injury and ECM expression[J]. Int J Clin Exp Med, 2016, 9(4): 7127-7136.
[8]	李丽, 常波. 过度训练动物模型制备的研究进展[J]. 沈阳体育学院学报, 2011, 30(5): 77-82.
[9]	Jiménez-Dalmaroni MJ, Gerswhin ME, Adamopoulos IE. The critical role of toll-like receptors-from microbial recognition to autoimmunity: a comprehensive review[J]. Autoimmun Rev, 2016, 15(1): 1-8.
[10]	蒋伟, 张弦, 周爱玲. TLR4/P38/JNK信号通路在海马神经元凋亡中的作用[J]. 中国应用生理学杂志, 2016, 32(6): 571-576.
[11]	郑妩媚, 初海平, 王燕, 等. 力竭运动后不同时相大鼠心肌p-p38MAPK、NF-κB、COX-2表达的动态变化[J].中国应用生理学杂志, 2016, 32(1): 88-91.
[12]	Sun LF, An DQ, Niyazi GL, et al. Effects of Tianxiangdan Granule treatment on atherosclerosis via NF-κB and p38 MAPK signaling pathways[J]. Mol Med Rep, 2018, 17(1): 1642-1650.
[13]	Zhang Y, Liu Z, Wu J, et al. New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity[J]. Eur J Med Chem, 2018, 148: 291-305.
[14]	Guimares MR, Leite FR, Spolidorio LC, et al. Curcumin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. Evidence for novel mechanisms involving SOCS-1, -3 and p38 MAPK[J]. Arch Oral Biol, 2013, 58(10): 1309-1317.
[15]	Song WB, Wang YY,Meng FS, et al. Curcumin protects intestinal mucosal barrier function of rat enteritis via activation of MKP-1 and attenuation of p38 and NF-κB activation[J]. PLoS One, 2010, 5(9): e12969.
[16]	Yu S, Wang X, He X, et al. Curcumin exerts anti-inflammatory and antioxidative properties in 1-methyl-4-phenylpyridinium ion (MPP+)-stimulated mesencephalic astrocytes by interference with TLR4 and downstream signaling pathway[J]. Cell Stress Chaperones, 2016, 21(4): 697-705.
[17]	Ni H, Jin W, Zhu T, et al. Curcumin modulates TLR4/NF-κB inflammatory signaling pathway following traumatic spinal cord injury in rats[J]. J Spinal Cord Med, 2015, 38(2): 199-206.
[18]	Zhou Y, Zhang T, Wang X, et al. Curcumin modulates macrophage polarization through the inhibition of the toll-like receptor 4 expression and its signaling pathways[J]. Cell Physiol Biochem, 2015, 36(2): 631-641.
[19]	Banchereau J, Pascual V, O' Garra A. From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines[J]. Nat Immunol, 2012, 13(10): 925-931.
[20]	Wang J, Kang YX, Pan W, et al. Enhancement of anti-inflammatory activity of curcumin using phosphatidylserine-containing nanoparticles in cultured macrophages[J]. Int J Mol Sci, 2016, 17(6): 969.
[21]	Larmonier CB, Uno JK, Lee KM, et al. Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection[J]. Am J Physiol Gastrointest Liver Physiol, 2008, 295(5): G1079-G1091.