Anti-Inflammatory and Anti-Oxidant Effects of Epilobium amurense subsp. cephalostigma via Activation of Nrf2/HO-1 and Inhibition of NF-κB/p38 MAPK Signaling in LPS-Stimulated Macrophages
Source abstract
Abstract
The genus Epilobium consists of approximately 200 species that are distributed worldwide. Some of these herbs have been used for the treatment of diarrhea, infection, irritation, and other disorders associated with inflammation. Unlike that of other Epilobium species, there is little scientific understanding of the pharmacological effect of Epilobium amurense subsp. cephalostigma (Hausskn.) C. J. Chen, Hoch & P. H. Raven. In this study, we demonstrated the anti-inflammatory and antioxidative properties of an E. amurense 95% ethanol extract (EACEE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and observed the underlying mechanism of this effect. We measured the productions of nitric oxide (NO) and reactive oxygen species, and examined the actions of EACEE on transcription factors in the macrophages. EACEE reduced NO production and inducible nitric oxide synthase protein levels via the inhibition of the nuclear factor (NF)-κB pathway. Additionally, EACEE suppressed redundant reactive oxygen species production and regulated nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling. Furthermore, EACEE significantly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). Overall, these results indicate that EACEE exerts anti-inflammatory and antioxidant effects via the activation of Nrf2/HO-1 and inhibition of NF-κB/p38 MAPK signaling.
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Research context
OpenAlex topics: Genomics, phytochemicals, and oxidative stress · Medicinal Plants and Bioactive Compounds · Phytochemistry and Biological Activities
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju-si 26339, Korea
AmcoBio Inc., Nambusunhwan-ro, Gwanak-gu, Seoul 08758, Korea
College of Pharmacy, Yanbian University, Yanji 133002, China
International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
Funding
National Research Foundation of Korea
References (38)
Show source-provided references
1. Phytochemistry, pharmacology and traditional uses of different Epilobium species (Onagraceae): A review10.1016/j.jep.2014.08.036 ↗
2. Kungnip Sumogwŏn (Korea) (2015). Hanbando Chasaeng Singmul Yŏngŏirum Mongnokchip [English Names for Korean Native Plants], Kungnip Sumogwŏn. Available online: https://www.nlb.gov.sg/biblio/203966604.
3. Inflammatory mechanisms: The molecular basis of inflammation and disease10.1301/nr.2007.dec.S140-S146 ↗
4. Inflammatory responses and inflammation-associated diseases in organs10.18632/oncotarget.23208 ↗
5. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling10.1016/j.cellsig.2012.01.008 ↗
6. Reactive oxygen species (ROS)-responsive biomaterials mediate tissue microenvironments and tissue regeneration10.1039/C9TB00847K ↗
7. Role of Nrf2 in Oxidative Stress and Toxicity10.1146/annurev-pharmtox-011112-140320 ↗
8. Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis10.1056/NEJMoa1114287 ↗
9. The cytoprotective role of the Keap1–Nrf2 pathway10.1007/s00204-011-0674-5 ↗
10. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution10.1111/j.1365-2443.2010.01473.x ↗
11. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy10.1016/j.canlet.2008.02.044 ↗
12. The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology10.1152/physrev.00044.2005 ↗
13. Reactive oxygen and nitrogen species regulate inducible nitric oxide synthase function shifting the balance of nitric oxide and superoxide production10.1016/j.abb.2009.11.019 ↗
14. NF-kappaB: A key role in inflammatory diseases10.1172/JCI11830 ↗
15. Reactive oxygen species, inflammation, and lung diseases10.2174/138161212802083716 ↗
16. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential10.1016/j.bcp.2010.07.014 ↗
17. Son, Y., Cheong, Y.-K., Kim, N.-H., Chung, H.-T., Kang, D.G., and Pae, H.-O. (2011). Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?. J. Signal Transduct., 2011.10.1155/2011/792639 ↗
18. The Control of Adaptive Immune Responses by the Innate Immune System10.1016/B978-0-12-387664-5.00003-0 ↗
19. Wang, M., Zhan, Z., Xiong, Y., Zhang, Y., and Li, X. (2019). Cytotoxic and anti-inflammatory constituents from Momordica cochinchinensis seeds. Fitoterapia, 139.10.1016/j.fitote.2019.104360 ↗
20. Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-κB, MAPKs and PI3K/Akt pathways and activating Nrf2/HO-1 signaling
21. Endotoxin signal transduction in macrophages10.1002/jlb.60.1.8 ↗
22. NO, ROS, and cell death associated with caspase-like activity increase in stress-induced microspore embryogenesis of barley
23. Oxidative Stress Increases Hepatocyte iNOS Gene Transcription and Promoter Activity10.1006/bbrc.1997.6562 ↗
24. Kunnumakkara, A.B., Sailo, B.L., Banik, K., Harsha, C., Prasad, S., Gupta, S.C., Bharti, A.C., and Aggarwal, B.B. (2018). Chronic diseases, inflammation, and spices: How are they linked?. J. Transl. Med., 16.10.1186/s12967-018-1381-2 ↗
25. Sharif, O., Bolshakov, V.N., Raines, S., Newham, P., and Perkins, N.D. (2007). Transcriptional profiling of the LPS induced NF-κB response in macrophages. BMC Immunol., 8.10.1186/1471-2172-8-1 ↗
26. Dissecting molecular cross-talk between Nrf2 and NF-kappaB response pathways10.1042/BST20150014 ↗
27. Inflammation meets cancer, with NF-kappaB as the matchmaker10.1038/ni.2060 ↗
28. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway10.1016/j.cellsig.2011.01.014 ↗
29. Directly interact with Keap1 and LPS is involved in the anti-inflammatory mechanisms of (-)-epicatechin-3-gallate in LPS-induced macrophages and endotoxemia10.1016/j.freeradbiomed.2016.02.010 ↗
30. The transcription factor Nrf2 is a therapeutic target against brain inflammation10.4049/jimmunol.181.1.680 ↗
31. Differential Modulation of Lipopolysaccharide-Induced Inflammatory Cytokine Production by and Antioxidant Activity of Fomentariol in RAW264.7 Cells10.5941/MYCO.2015.43.4.450 ↗
32. Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages10.1016/j.bbrc.2009.10.053 ↗
33. Inhibition of LPS-stimulated ROS production by fluorinated and hydroxylated chalcones in RAW 264.7 macrophages with structure-activity relationship study10.1016/j.bmcl.2017.01.061 ↗
34. Ngkelo, A., Meja, K., Yeadon, M., Adcock, I., and Kirkham, P.A. (2012). LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Gialpha dependent PI-3kinase signalling. J. Inflamm., 9.10.1186/1476-9255-9-1 ↗
35. Endogenous Hydrogen Sulfide Ameliorates NOX4 Induced Oxidative Stress in LPS-Stimulated Macrophages and Mice10.1159/000489980 ↗
36. MAPK signalling pathways as molecular targets for anti-inflammatory therapy—from molecular mechanisms to therapeutic benefits10.1016/j.bbapap.2005.08.017 ↗
37. Lee, I.T., Shih, R.H., Lin, C.C., Chen, J.T., and Yang, C.M. (2012). Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells. Cell Commun. Signal., 10.10.1186/1478-811X-10-33 ↗
38. Mechanism of Action of Sulforaphane: Inhibition of p38 Mitogen-Activated Protein Kinase Isoforms Contributing to the Induction of Antioxidant Response Element–Mediated Heme Oxygenase-1 in Human Hepatoma HepG2 Cells10.1158/0008-5472.CAN-05-3513 ↗