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Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages.
Int J Immunopathol Pharmacol 2011 Apr-Jun; 24(2):345-56IJ

Abstract

Eugenol and isoeugenol, two components of clover oil, have been reported to possess several biomedical properties, such as anti-inflammatory, antimicrobial and antioxidant effects. This study aims to examine the anti-inflammatory effects of eugenol, isoeugenol and four of their derivatives on expression of inducible nitric oxide synthase (iNOS) activated by lipopolysaccharide (LPS) in mouse macrophages (RAW 264.7), and to investigate molecular mechanisms underlying these effects. We found that two derivatives, eugenolol and glyceryl-isoeugenol, had potent inhibitory effects on LPS-induced upregulation of nitrite levels, iNOS protein and iNOS mRNA. In addition, they both suppressed the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced by LPS. Moreover, they both attenuated the DNA binding of NF-kB and AP-1, phosphorylation of inhibitory kB-alpha (IkB-alpha), and nuclear translocation of p65 protein induced by LPS. Finally, we demonstrated that glyceryl-isoeugenol suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK, whereas eugenolol suppressed the phosphorylation of ERK1/2 and p38 MAPK. Taken together, these results suggest that that eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kB and AP-1 through inhibition of MAPKs and Akt/IkB-alpha signaling pathways. Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases.

Authors+Show Affiliations

Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, and Department of Paediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21658309

Citation

Yeh, J L., et al. "Eugenolol and Glyceryl-isoeugenol Suppress LPS-induced iNOS Expression By Down-regulating NF-kappaB and AP-1 Through Inhibition of MAPKS and AKT/IkappaBalpha Signaling Pathways in Macrophages." International Journal of Immunopathology and Pharmacology, vol. 24, no. 2, 2011, pp. 345-56.
Yeh JL, Hsu JH, Hong YS, et al. Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages. Int J Immunopathol Pharmacol. 2011;24(2):345-56.
Yeh, J. L., Hsu, J. H., Hong, Y. S., Wu, J. R., Liang, J. C., Wu, B. N., ... Liou, S. F. (2011). Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages. International Journal of Immunopathology and Pharmacology, 24(2), pp. 345-56.
Yeh JL, et al. Eugenolol and Glyceryl-isoeugenol Suppress LPS-induced iNOS Expression By Down-regulating NF-kappaB and AP-1 Through Inhibition of MAPKS and AKT/IkappaBalpha Signaling Pathways in Macrophages. Int J Immunopathol Pharmacol. 2011;24(2):345-56. PubMed PMID: 21658309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages. AU - Yeh,J L, AU - Hsu,J H, AU - Hong,Y S, AU - Wu,J R, AU - Liang,J C, AU - Wu,B N, AU - Chen,I J, AU - Liou,S F, PY - 2011/6/11/entrez PY - 2011/6/11/pubmed PY - 2011/8/19/medline SP - 345 EP - 56 JF - International journal of immunopathology and pharmacology JO - Int J Immunopathol Pharmacol VL - 24 IS - 2 N2 - Eugenol and isoeugenol, two components of clover oil, have been reported to possess several biomedical properties, such as anti-inflammatory, antimicrobial and antioxidant effects. This study aims to examine the anti-inflammatory effects of eugenol, isoeugenol and four of their derivatives on expression of inducible nitric oxide synthase (iNOS) activated by lipopolysaccharide (LPS) in mouse macrophages (RAW 264.7), and to investigate molecular mechanisms underlying these effects. We found that two derivatives, eugenolol and glyceryl-isoeugenol, had potent inhibitory effects on LPS-induced upregulation of nitrite levels, iNOS protein and iNOS mRNA. In addition, they both suppressed the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced by LPS. Moreover, they both attenuated the DNA binding of NF-kB and AP-1, phosphorylation of inhibitory kB-alpha (IkB-alpha), and nuclear translocation of p65 protein induced by LPS. Finally, we demonstrated that glyceryl-isoeugenol suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK, whereas eugenolol suppressed the phosphorylation of ERK1/2 and p38 MAPK. Taken together, these results suggest that that eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kB and AP-1 through inhibition of MAPKs and Akt/IkB-alpha signaling pathways. Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases. SN - 0394-6320 UR - https://www.unboundmedicine.com/medline/citation/21658309/Eugenolol_and_glyceryl_isoeugenol_suppress_LPS_induced_iNOS_expression_by_down_regulating_NF_kappaB_AND_AP_1_through_inhibition_of_MAPKS_and_AKT/IkappaBalpha_signaling_pathways_in_macrophages_ L2 - http://journals.sagepub.com/doi/full/10.1177/039463201102400208?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -