Anti-Inflammatory Activity of Cirsium nipponicum Extracts via Inhibition of JNK and NF-κB Signaling and Activation of ROS/PI3K/Nrf2/HO-1 Pathways in RAW264.7 Cells

Sang Hun Lee; Jeong Won Choi; Hyeok Jin Choi; So Jung Park; Jin Hyuk Hwang; Yeong-Su Kim; Kwangmo Hwang; Jin Boo Jeong

doi:10.7732/kjpr.2025.38.1.001

All Issue

2025 Vol.38, Issue 1 Next Page

Research Article

Anti-Inflammatory Activity of Cirsium nipponicum Extracts via Inhibition of JNK and NF-κB Signaling and Activation of ROS/PI3K/Nrf2/HO-1 Pathways in RAW264.7 Cells RAW264.7 세포에서 물엉겅퀴(Cirsium nipponicum) 추출물의 JNK와 NF-κB 신호전달 억제와 ROS/PI3K/Nrf2/HO-1 신호전달 활성화를 통한 항염증 활성

1 February 2025. pp. 1-9

PDF XML

Abstract

Chronic inflammation serves as both a catalyst and an exacerbating factor for numerous diseases, posing significant health risks. This study investigates the anti-inflammatory properties of CNL, aiming to elucidate their mechanistic roles in inflammation modulation in LPS-stimulated RAW264.7 cells. CNL inhibited excessive NO production and iNOS expression induced by LPS in RAW264.7 cells. While CNL failed to inhibit LPS-induced phosphorylation of ERK1/2 and p38 in RAW264.7 cells, CNL significantly reduced the phosphorylation of JNK and p65. CNL elevated the protein levels of HO-1 and nuclear Nrf2 in RAW264.7 cells. Moreover, the inhibition of HO-1 by ZnPP attenuated the NO-suppressive activity induced by CNL. In addition, CNL induced PI3K activation, and inhibition of PI3K by LY294002 reduced the elevation of HO-1 and nuclear Nrf2 protein levels mediated by CNL. The inhibition of ROS by NAC reduced the PI3K activation and the elevation of HO-1 and nuclear Nrf2 protein levels induced by CNL. Taken together, these findings suggest that CNL inhibit NO production by suppressing iNOS expression through the inhibition of JNK and NF-κB signaling pathways and by activating the ROS/PI3K/Nrf2/HO-1 signaling cascade.

Keywords

Anti-inflammation

Cirsium nipponicum

Macrophages

References

Baek, S.H., T. Park, M.G. Kang, and D. Park. 2020. Anti-inflammatory activity and ROS regulation effect of sinapaldehyde in LPS-stimulated RAW264.7 macrophages. Molecules 25(18):4089.

10.3390/molecules2518408932906766PMC7570554

Cao, Y., J. Chen, G. Ren, Y. Zhang, X. Tan, and L. Yang. 2019. Punicalagin prevents inflammation in LPS-induced RAW264.7 macrophages by inhibiting FoxO3a/autophagy signaling pathway. Nutrients 11(11):2794.

10.3390/nu1111279431731808PMC6893462

Han, Y., X. Li, X. Zhang, Y. Gao, R. Qi, R. Cai, and Y. Qi. 2020. Isodeoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber Linn., inhibits pro-inflammatory mediators' production through both NF-κB and AP-1 pathways in LPS-activated macrophages. Int. Immunopharmacol. 84:106528.

10.1016/j.intimp.2020.10652832335480

Jin, C.H., H.J. Lee, Y.D. Park, D.S. Choi, D.S. Kim, S.Y. Kang, K.I. Seo, and I.Y. Jeong. 2010. Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages through the heme oxygenase-1 induction and inhibition of the interferon-β-STAT-1 pathway. J. Agric. Food Chem. 58:860-867.

10.1021/jf903333320030328

Jin, C.H., Y.K. So, S.N. Han, and J.B. Kim. 2016. Isoegomaketone upregulates heme oxygenase-1 in RAW264.7 cells via ROS/p38 MAPK/Nrf2 pathway. Biomol. Ther. 24:510-516.

10.4062/biomolther.2015.19427582555PMC5012876

Johnson, J.A., D.A. Johnson, A.D. Kraft, M.J. Calkins, R.J. Jakel, M.R. Vargas, and P.C. Chen. 2008. The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann. N. Y. Acad. S. 1147:61-69.

10.1196/annals.1427.03619076431PMC2605641

Kim, B., Y. Lee, B. Koh, S.Y. Jhang, C.H. Lee, S. Kim, W.J. Chi, S. Cho, H. Kim, and J. Yu. 2023a. Distinctive origin and evolution of endemic thistle of Korean volcanic island: Structural organization and phylogenetic relationships with complete chloroplast genome. PLoS One 18: e0277471.

10.1371/journal.pone.027747136913349PMC10010555

Kim, C.H., Y.K. Lee, M.J. Kim, J.S. Choi, B.S. Hwang, P.Y. Cho, Y.J. Kim, and Y.T. Jeong. 2023b. Evaluation antioxidant and anti-inflammatory activity of ethanolic extracts of Myriophyllum spicatum L. in lipopolysaccharide-stimulated RAW 264.7 cells. Korean J. Plant Res. 36(1):15-25.

Lee, D.S., K.S. Kim, B. Li, H.G. Choi, S. Keo, K.Y. Jun, J.H. Park, and Y.C. Kim. 2012. Anti-inflammatory effect of the Cirsium japonicum var. ussuriense 70% ethanolic extracts in RAW264.7 cells by heme oxygenase-1 expression. Kor. J. Pharmacogn. 43(1):39-45.

Liu, X.M., K.J. Peyton, A.R. Shebib, H. Wang, and W. Durante. 2011. Compound C stimulates heme oxygenase-1 gene expression via the Nrf2-ARE pathway to preserve human endotherial cell survival. Biochem. Pharmacol. 82:371-379.

10.1016/j.bcp.2011.05.01621635873PMC3138903

Meng, X., M. Wang, X. Wang, G. Sun, J. Ye, X. Xu, and X. Sun. 2014. Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia-reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathways. Free Radic. Res. 48:823-838.

10.3109/10715762.2014.91185324720662

Minhas, R., Y. Bansal, and G. Bansal. 2020. Inducible nitric oxide synthase inhibitors: A comprehensive update. Med. Res. Rev. 40:823-855.

10.1002/med.2163631502681

Park, M.Y., S.E. Ha, H.H. Kim, P.D. Bhosale, A. Abusaliya, S.H. Jeong, J.S. Park, J.D. Heo, and G.S. Kim. 2022. Scutellarein inhibits LPS-induced inflammation through NF-κB/MAPKs signaling pathway in RAW264.7 cells. Molecules 27:3782.

10.3390/molecules2712378235744907PMC9227861

Park, P.H., H.S. Kim, X.Y. Jin, F. Jin, J. Hur, G. Ko, and D.H. Sohn DH. 2009. KB-34, a newly synthesized chalcone derivative, inhibits lipopolysaccharide-stimulated nitric oxide production in RAW264.7 macrophages via heme oxygenase-1 induction and blockade of activator protein-1. Eur. J. Pharmacol. 606:215-224.

10.1016/j.ejphar.2008.12.03419174156

Riera-Romo, M., D. Pérez-Martínez, and C.C. Ferrer. 2016. Innate immunity in vertebrates: An overview. Immunology 148:125-139.

10.1111/imm.1259726878338PMC4863567

True, A.L., M. Olive, M. Boehm, H. San, R.J. Westrick, N. Raghavachari, X. Xu, E.G. Lynn, M.N. Sack, P.J. Munson, M.T. Gladwin, and E.G. Nabel. 2007. Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide. Circ. Res. 101:893-901.

10.1161/CIRCRESAHA.107.15899817885218

Tsoyi, K., H.J. Kim, J.S. Shin, D.H. Kim, H.J. Cho, S.S. Lee, S.K Ahn, H.S. Y. Choi, J.H. Lee, H.G. Seo, and K.C. Chang KC. 2008. HO-1 and JAK-2/STAT-1 signals are involved in preferential inhibition of iNOS over COX-2 gene expression by newly synthesized tetrahydroisoquinoline alkaloid, CKD712, in cells activated with lipopolysaccharide. Cell. Signal. 20:1839-1847.

10.1016/j.cellsig.2008.06.01218634870

Xie, C., X. Li, J. Zhu, J. Wu, S. Geng, and C. Zhong. 2019. Magnesium isoglycyrrhizinate suppresses LPS-induced inflammation and oxidative stress through inhibiting NF-κB and MAPK pathways in RAW264.7 cells. Bioorg. Med. Chem. 27:516-524.

10.1016/j.bmc.2018.12.03330617018

Xu, X., H. Li, X. Hou, D. Li, S. He, C. Wan, P. Yin, M. Liu, F. Liu, and J. Xu. 2015. Punicalagin induces Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway and inhibits LPS-induced oxidative stress in RAW264.7 macrophages. Mediat. Inflamm. 2015:380218.

10.1155/2015/38021825969626PMC4417599

Information

Publisher :The Plant Resources Society of Korea
Publisher(Ko) :한국자원식물학회
Journal Title :Korean Journal of Plant Resources
Journal Title(Ko) :한국자원식물학회지
Volume : 38
No :1
Pages :1-9
Received Date : 2024-11-22
Revised Date : 2024-12-05
Accepted Date : 2024-12-06
DOI :https://doi.org/10.7732/kjpr.2025.38.1.001

Korean Journal of Plant Resources ISSN:1226-3591(Print) 2287-8203(Online) 한국자원식물학회지

All Issue