Sinomenine effectively inhibits interleukin-1beta-induced apoptosis in nucleus pulposus cells

doi:10.12307/2023.873

Abstract

Abstract: BACKGROUND: Intervertebral disc degeneration is the basis of spinal degenerative diseases; however, there is no effective treatment.
OBJECTIVE: To investigate whether sinomenine can inhibit interleukin-1β-induced apoptosis in nucleus pulposus cells and its molecular mechanism.
METHODS: Rat nucleus pulposus cells were cultured in vitro by trypsin combined with type II collagenase digestion, and the cell growth curve was plotted. An appropriate sinomenine concentration was determined using the cell counting kit-8 kit. Nucleus pulposus cells were divided into control group, sinomenine group, interleukin-1β group, sinomenine+interleukin-1β group, zinc protoporphyrin group, zinc protoporphyrin+sinomenine group, zinc protoporphyrin+interleukin-1β group, and sinomenine+zinc protoporphyrin+interleukin-1β group. Proliferative activity, reactive oxygen species content, apoptosis rate, and heme oxygenase-1 expression in nucleus pulposus cells were detected.
RESULTS AND CONCLUSION: The rat nucleus pulposus cells cultured in vitro were polygonal, triangular, and short wedge-shaped, and the cell growth showed an “S” curve. The cells grew slowly in the first 3 days of culture, rapidly in 4-6 days, and slowly again in 7-8 days. The cells then entered the “platform stage” where the number of cells no longer increased. The proliferative activity of myeloid cells showed no significant changes when the concentration of sinomenine was ≤ 80 μmol/L (P > 0.05). Interleukin-1β significantly reduced the proliferative activity of nucleus pulposus cells, increased the content of reactive oxygen species and led to apoptosis (P < 0.01). Sinomenine intervention not only promoted heme oxygenase-1 expression (P < 0.05) but also inhibited interleukin-1β-induced decrease in proliferative activity and increase in reactive oxygen species content and apoptosis rate in nucleus pulposus cells (P < 0.05). These effects could be reversed by zinc protoporphyrin (P < 0.01).

Key words: sinomenine, interleukin-1β, heme oxygenase-1, nucleus pulposus cell, cell proliferation, apoptosis, reactive oxygen species, intervertebral disc, intervertebral disc degeneration

CLC Number:

Wang Qian, Lu Ziang, Li Lihe, Lyu Chaoliang, Wang Meng, Zhang Cunxin. Sinomenine effectively inhibits interleukin-1beta-induced apoptosis in nucleus pulposus cells[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(2): 224-230.

Figures/Tables 5

References

[1] CHEN BL, GUO JB, ZHANG HW, et al. Surgical versus non-operative treatment for lumbar disc herniation: a systematic review and meta-analysis. Clin Rehabil. 2018;32(2):146-160.
[2] JUNGEN MJ, Ter MEULEN BC, van OSCH T, et al. Inflammatory biomarkers in patients with sciatica: a systematic review. BMC Musculoskelet Disord. 2019;20(1):156.
[3] DENES K, ARANYI Z, CSILLIK A, et al. Serum biomarkers in acute low back pain and sciatica. Orv Hetil. 2020;161(13):483-490.
[4] ZHAO L, MANCHIKANTI L, KAYE AD, et al. Treatment of Discogenic Low Back Pain: Current Treatment Strategies and Future Options-a Literature Review. Curr Pain Headache Rep. 2019;23(11):86.
[5] LIU HY, KANG HL, SONG C, et al. Urolithin A Inhibits the Catabolic Effect of TNFalpha on Nucleus Pulposus Cell and Alleviates Intervertebral Disc Degeneration in vivo. Front Pharmacol. 2018;9:1043.
[6] LI P, HOU G, ZHANG RJ, et al. High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway. Arthritis Res Ther. 2017;19(1):209.
[7] HIDER SL, KONSTANTINOU K, HAY EM, et al. Inflammatory
biomarkers do not distinguish between patients with sciatica and referred leg pain within a primary care population: results from a nested study within the ATLAS cohort. BMC Musculoskelet Disord. 2019;20(1):202.
[8] WANG YJ, CHE MX, XIN JG, et al. The role of IL-1beta and TNF-alpha in intervertebral disc degeneration. Biomed Pharmacother. 2020;131: 110660.
[9] ZHAO KC, AN R, XIANG Q, et al. Acid-sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration. Cell Prolif. 2021; 4(1):e12941.
[10] XU QL, XING HY, WU JQ, et al. miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells. Front Cell Dev Biol. 2020;8:871.
[11] LI ZW, WANG JM, MA YM. Montelukast attenuates interleukin IL-1beta-induced oxidative stress and apoptosis in chondrocytes by inhibiting CYSLTR1 (Cysteinyl Leukotriene Receptor 1) and activating KLF2 (Kruppel Like Factor 2). Bioengineered. 2021;12(1):8476-8484.
[12] ZHU WR, TANG H, LI JC, et al. Ellagic acid attenuates interleukin-1beta-induced oxidative stress and exerts protective effects on chondrocytes through the Kelch-like ECH-associated protein 1 (Keap1)/ Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Bioengineered. 2022;13(4):9233-9247.
[13] JIANG W, FAN WM, GAO TL, et al. Analgesic Mechanism of Sinomenine against Chronic Pain. Pain Res Manag. 2020;2020:1876862.
[14] IINO T, SAKO T. Inhibition and resumption of processing of the staphylokinase in some Escherichia coli prlA suppressor mutants. J Biol Chem. 1988;263(35):19077-19082.
[15] FAN H, SHU Q, GUAN XL, et al. Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System. Cell Mol Neurobiol. 2017;37(8):1387-1398.
[16] LIU WW, ZHANG YJ, ZHU WN, et al. Sinomenine Inhibits the Progression of Rheumatoid Arthritis by Regulating the Secretion of Inflammatory Cytokines and Monocyte/Macrophage Subsets. Front Immunol. 2018; 9:2228.
[17] ZENG MY, TONG QY. Anti-inflammation Effects of Sinomenine on Macrophages through Suppressing Activated TLR4/NF-kappaB Signaling Pathway. Curr Med Sci. 2020;40(1):130-137.
[18] FAN H, SHU Q, GUAN XL, et al. Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System. Cell Mol Neurobiol. 2017;37(8):1387-1398.
[19] PENG Y, OU H, YANG MS, et al. Inhibition of lipopolysaccharide-induced inflammation in RAW264.7 macrophages by sinomenine through regulating heme oxygenase-1 expression and autophagy. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018;43(9):964-970.
[20] KIM YK, KANG DM, LEE I, et al. Differences in the Incidence of Symptomatic Cervical and Lumbar Disc Herniation According to Age, Sex and National Health Insurance Eligibility: A Pilot Study on the Disease’s Association with Work. Int J Environ Res Public Health. 2018;15(10):2094.
[21] BAI XL, DING WY, YANG SD, et al. Higenamine inhibits IL-1beta-induced inflammation in human nucleus pulposus cells. Biosci Rep. 2019;39(6): BSR20190857.
[22] ZHOU YF, CHEN ZQ, YANG X, et al. Morin attenuates pyroptosis of nucleus pulposus cells and ameliorates intervertebral disc degeneration via inhibition of the TXNIP/NLRP3/Caspase-1/IL-1beta signaling pathway. Biochem Biophys Res Commun. 2021;559:106-112.
[23] MA ZX, TANG P, DONG W, et al. SIRT1 alleviates IL-1beta induced nucleus pulposus cells pyroptosis via mitophagy in intervertebral disc degeneration. Int Immunopharmacol. 2022;107:108671.
[24] FORRESTER SJ, KIKUCHI DS, HERNANDES MS, et al. Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ Res. 2018;122(6): 877-902.
[25] DAI YQ, ZHANG J, XIANG J, et al. Calcitriol inhibits ROS-NLRP3-IL-1beta signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells. Redox Biol. 2019;21:101093.
[26] WU XX, ZHANG HQ, QI W, et al. Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis. Cell Death Dis. 2018;9(2):171.
[27] KANG L, HU J, WENG YX, et al. Sirtuin 6 prevents matrix degradation through inhibition of the NF-kappaB pathway in intervertebral disc degeneration. Exp Cell Res. 2017;352(2):322-332.
[28] LI Z, WANG X, PAN H, et al. Resistin promotes CCL4 expression through toll-like receptor-4 and activation of the p38-MAPK and NF-kappaB signaling pathways: implications for intervertebral disc degeneration. Osteoarthritis Cartilage. 2017;25(2):341-350.
[29] LUO X, HUAN L, LIN F, et al. Ulinastatin Ameliorates IL-1beta-Induced Cell Dysfunction in Human Nucleus Pulposus Cells via Nrf2/NF-kappaB Pathway. Oxid Med Cell Longev. 2021;2021:5558687.
[30] ZHANG CX, WANG T, MA JF, et al. Protective effect of CDDO-ethyl amide against high-glucose-induced oxidative injury via the Nrf2/HO-1 pathway. Spine J. 2017;17(7):1017-1025.
[31] EARLY JO, MENON D, WYSE CA, et al. Circadian clock protein BMAL1 regulates IL-1beta in macrophages via NRF2. Proc Natl Acad Sci U S A. 2018,115(36):E8460-E8468.
[32] YUAN ML, ZHAO B, JIA HP, et al. Sinomenine ameliorates cardiac hypertrophy by activating Nrf2/ARE signaling pathway. Bioengineered. 2021;12(2):12778-12788.
[33] GAO ZX, LIN YC, ZHANG P, et al. Sinomenine ameliorates intervertebral disc degeneration via inhibition of apoptosis and autophagy in vitro and in vivo. Am J Transl Res. 2019;11(9):5956-5966.
[34] HOU XF, SHEN YC, SUN ML, et al. Effect of regulating macrophage polarization phenotype on intervertebral disc degeneration. Immun Inflamm Dis. 2022;10(11):e714.