Deciphering the mechanism of cimifugin in mitigating LPS-induced neuroinflammation in BV-2 cells
Main Article Content
Keywords
BV-2 Cells, Cimifugin, oxidative stress, sepsis, SIRT1/Nrf2 pathway
Abstract
Purpose: Sepsis often triggers a systemic inflammatory response leading to multi-organ dysfunction, with complex and not fully understood pathogenesis. This study investigates the therapeutic effects of cimifugin on BV-2 cells under sepsis-induced stress conditions.
Methods: We utilized a BV-2 microglial cell model treated with lipopolysaccharide (LPS) to mimic sepsis. Assessments included cellular vitality, inflammatory cytokine quantification (6 interleukin [6IL]-1β, interleukin 6 [IL-6], and tumor necrosis factor-α [TNF-α]) via enzyme-linked-immunosorbent serologic assay, and analysis of mRNA expression using real-time polymerase chain reaction. Oxidative stress and mitochondrial function were also evaluated to understand the cellular effects of cimifugin.
Results: Cimifugin significantly attenuated LPS-induced inflammatory responses, oxidative stress, and mitochondrial dysfunction. It enhanced cell viability and modulated the secretion and gene expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, cimifugin activated the deacetylase sirtuin 1–nuclear factor erythroid 2-related factor 2 pathway, contributing to its protective effects against mitochondrial damage.
Conclusion: Cimifugin demonstrates the potential of being an effective treatment for sepsis--induced neuroinflammation, warranting further investigation.
References
2. World Health Organization (WHO). WHO calls for global action on sepsis – Cause of 1 in 5 deaths worldwide [Internet]. [cited 2020 Sep 8]. Available from: https://www.who.int/news/item/08-09-2020-who-calls-for-global-action-on-sepsis---cause-of-1-in-5-deaths-worldwide
3. Wu Q, Wang Y, Li Q. Matairesinol exerts anti-inflammatory and antioxidant effects in sepsis-mediated brain injury by repressing the MAPK and NF-κB pathways through up--regulating AMPK. Aging (Albany NY). 2021;13(20):23780–95. 10.18632/aging.203649
4. Shi Y, Yin HQ. Dimethyl itaconate inhibits LPS-induced inflammatory release and apoptosis in alveolar type II epithelial and bronchial epithelial cells by activating pulmonary surfactant proteins A and D. Allergol Immunopathol (Madr). 2022;50(6):176–86. 10.15586/aei.v50i6.586
5. Zhao P, Li X, Yang Q, Lu Y, Wang G, Yang H, et al. Malvidin alleviates mitochondrial dysfunction and ROS accumulation through activating AMPK-α/UCP2 axis, thereby resisting inflammation and apoptosis in SAE mice. Front Pharmacol. 2022;13:1038802. 10.3389/fphar.2022.1038802
6. Rehman F, Goyal A, Gauba K, Jain K, Kapur A. Safety and efficacy of IV dexmedetomidine as an adjunct to propofol to sedate anxious and uncooperative pediatric dental patients: A randomized controlled trial. J Clin Pediatr Dent (JOCPD). 2022;45(6):428–32. 10.17796/1053-4625-45.6.10
7. Miller DM, Singh IN, Wang JA, Hall ED. Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice. Exp Neurol. 2015;264:103–10. 10.1016/j.expneurol.2014.11.008
8. Chen H, Dong B, Shi Y, Yu Y, Xie K. Hydrogen alleviates neuronal injury and neuroinflammation induced by microglial activation via the nuclear factor erythroid 2-related factor 2 pathway in sepsis-associated encephalopathy. Neuroscience. 2021;466:87–100. 10.1016/j.neuroscience.2021.05.003
9. Chen X, Huang J. Mangiferin inhibits hypoxia/reoxygenation-induced alveolar epithelial cell injury via the SIRT1/AMPK signaling pathway. Exp Ther Med. 2021;22(5):1220. 10.3892/etm.2021.10654
10. Han B, Dai Y, Wu H, Zhang Y, Wan L, Zhao J, et al. Cimifugin inhibits inflammatory responses of RAW264.7 cells induced by lipopolysaccharide. Med Sci Monit. 2019;25:409–17. 10.12659/MSM.912042
11. Liu A, Zhao W, Zhang B, Tu Y, Wang Q, Li J. Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway. Biosci Rep. 2020;40(6):BSR20200471. 10.1042/BSR20200471
12. Jia Z, Tie C, Wang C, Wu C, Zhang J. Perturbed lipidomic profiles in rats with chronic cerebral ischemia are regulated by Xiao-Xu-Ming decoction. Front Pharmacol. 2019;10:264. 10.3389/fphar.2019.00264
13. AP IJ, Guo D. Drug-target association kinetics in drug discovery. Trends Biochem Sci. 2019;44(10):861–71. 10.1016/j.tibs.2019.04.004
14. Wilson JG, Simpson LJ, Ferreira AM, Rustagi A, Roque J, Asuni A, et al. Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight. 2020;5(17):e140289. 10.1172/jci.insight.140289
15. Zhuang X, Yu Y, Jiang Y, Zhao S, Wang Y, Su L, et al. Molecular hydrogen attenuates sepsis-induced neuroinflammation through regulation of microglia polarization through an mTOR-autophagy-dependent pathway. Int Immunopharmacol. 2020;81:106287. 10.1016/j.intimp.2020.106287
16. Izadparast F, Riahi-Zajani B, Yarmohammadi F, Hayes AW, Karimi G. Protective effect of berberine against LPS-induced injury in the intestine: A review. Cell Cycle. 2022;21(22):2365–78. 10.1080/15384101.2022.2100682
17. Jiao H, Jiang D, Hu X, Du W, Ji L, Yang Y, et al. Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell. 2021;184(11):2896–910.e13. 10.1016/j.cell.2021.04.027
18. Sang A, Wang Y, Wang S, Wang Q, Wang X, Li X, et al. Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways. Cell Signal. 2022;96:110363. 10.1016/j.cellsig.2022.110363
19. Barrera J, Figueiredo AJ, Clemente FM, Field A, Valenzuela L, Sarmento H. Injury prevention programmes in male soccer players: An umbrella review of systematic reviews. J Men Health. 2022;18(10):1–17. 10.31083/j.jomh1810200
20. Chen H, Chen X, Yuan X, Zhang Y, Wang G. Estrogen receptor 1 and Aurora kinase A as potential diagnostic biomarkers for cervical cancer. Eur J Gynaecol Oncol. 2022;43(5):32–41. 10.22514/ejgo.2022.025
21. Qiongyue Z, Xin Y, Meng P, Sulin M, Yanlin W, Xinyi L, et al. Post-treatment with irisin attenuates acute kidney injury in sepsis mice through anti-ferroptosis via the SIRT1/Nrf2 Pathway. Front Pharmacol. 2022;13:857067. 10.3389/fphar.2022.857067