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Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages.
Int Immunopharmacol 2009; 9(9):1049-57II

Abstract

Several sesquiterpene lactones that have been isolated from medicinal plants are known to have many pharmacological activities. In this study, we investigated the anti-inflammatory effects of zedoarondiol, a sesquiterpene lactone isolated from the rhizoma of Curcuma heyneana, in lipopolysaccharide (LPS)-stimulated macrophage cells. Zedoarondiol dose-dependently inhibited LPS-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) productions in RAW 264.7 macrophage and in mouse peritoneal macrophage cells. Consistent with these findings, in RAW 264.7 cells, zedoarondiol suppressed the LPS-stimulated protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the mRNA expressions of iNOS, COX-2, TNF-alpha, IL-6, and IL-1beta in a concentration-dependent manner. Moreover, molecular data revealed that zedoarondiol inhibited LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB), and this effect was accompanied by decreases in the degradation and phosphorylation of inhibitory kappaB (IkappaB)-alpha, and in the subsequent blocking of NF-kappaB translocations to the nucleus. Furthermore, zedoarondiol attenuated the phosphorylations of IkappaB kinase (IKK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) in LPS-stimulated RAW 264.7 cells. Taken together, the findings of the present study indicate that zedoarondiol inhibits iNOS, COX-2, and pro-inflammatory cytokine expressions by suppressing the phosphorylations of IKK and MAPKs, and by subsequently inactivating the NF-kappaB pathway. These relations reveal, in part, the mechanism underlying the anti-inflammatory properties of zedoarondiol.

Authors+Show Affiliations

Department of Pharmaceutical Biochemistry, Kyung-Hee University, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19398040

Citation

Cho, Woong, et al. "Zedoarondiol Isolated From the Rhizoma of Curcuma Heyneana Is Involved in the Inhibition of iNOS, COX-2 and Pro-inflammatory Cytokines Via the Downregulation of NF-kappaB Pathway in LPS-stimulated Murine Macrophages." International Immunopharmacology, vol. 9, no. 9, 2009, pp. 1049-57.
Cho W, Nam JW, Kang HJ, et al. Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages. Int Immunopharmacol. 2009;9(9):1049-57.
Cho, W., Nam, J. W., Kang, H. J., Windono, T., Seo, E. K., & Lee, K. T. (2009). Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages. International Immunopharmacology, 9(9), pp. 1049-57. doi:10.1016/j.intimp.2009.04.012.
Cho W, et al. Zedoarondiol Isolated From the Rhizoma of Curcuma Heyneana Is Involved in the Inhibition of iNOS, COX-2 and Pro-inflammatory Cytokines Via the Downregulation of NF-kappaB Pathway in LPS-stimulated Murine Macrophages. Int Immunopharmacol. 2009;9(9):1049-57. PubMed PMID: 19398040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages. AU - Cho,Woong, AU - Nam,Joo-Won, AU - Kang,Hyun-Jun, AU - Windono,Tri, AU - Seo,Eun-Kyoung, AU - Lee,Kyung-Tae, Y1 - 2009/04/24/ PY - 2009/02/27/received PY - 2009/04/21/revised PY - 2009/04/21/accepted PY - 2009/4/29/entrez PY - 2009/4/29/pubmed PY - 2010/1/15/medline SP - 1049 EP - 57 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 9 IS - 9 N2 - Several sesquiterpene lactones that have been isolated from medicinal plants are known to have many pharmacological activities. In this study, we investigated the anti-inflammatory effects of zedoarondiol, a sesquiterpene lactone isolated from the rhizoma of Curcuma heyneana, in lipopolysaccharide (LPS)-stimulated macrophage cells. Zedoarondiol dose-dependently inhibited LPS-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) productions in RAW 264.7 macrophage and in mouse peritoneal macrophage cells. Consistent with these findings, in RAW 264.7 cells, zedoarondiol suppressed the LPS-stimulated protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the mRNA expressions of iNOS, COX-2, TNF-alpha, IL-6, and IL-1beta in a concentration-dependent manner. Moreover, molecular data revealed that zedoarondiol inhibited LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB), and this effect was accompanied by decreases in the degradation and phosphorylation of inhibitory kappaB (IkappaB)-alpha, and in the subsequent blocking of NF-kappaB translocations to the nucleus. Furthermore, zedoarondiol attenuated the phosphorylations of IkappaB kinase (IKK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) in LPS-stimulated RAW 264.7 cells. Taken together, the findings of the present study indicate that zedoarondiol inhibits iNOS, COX-2, and pro-inflammatory cytokine expressions by suppressing the phosphorylations of IKK and MAPKs, and by subsequently inactivating the NF-kappaB pathway. These relations reveal, in part, the mechanism underlying the anti-inflammatory properties of zedoarondiol. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/19398040/Zedoarondiol_isolated_from_the_rhizoma_of_Curcuma_heyneana_is_involved_in_the_inhibition_of_iNOS_COX_2_and_pro_inflammatory_cytokines_via_the_downregulation_of_NF_kappaB_pathway_in_LPS_stimulated_murine_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(09)00160-X DB - PRIME DP - Unbound Medicine ER -