Luteolin Isolated from the Flowers of Lonicera Japonica Suppresses Inflammatory Mediator Release by Blocking NF-kappaB and MAPKs Activation Pathways in HMC-1 Cells

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2010 Jan 30

PMID 20110898

Citations 49

Authors

Ok-Hwa Kang

Jang-Gi Choi

John-Hwa Lee

Dong-Yeul Kwon

Affiliations

Soon will be listed here.

Abstract

Luteolin (3',4',5,7-tetrahydroxylflavone) is a plant flavonoid and pharmacologically active agent that has been isolated from several plant species. In the present study, the effect of luteolin from the flowers of Lonicera japonica on phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell activation was examined. Luteolin significantly inhibited the induction of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by PMA plus A23187. Moreover, luteolin attenuated cyclooxygenase (COX)-2 expression and intracellular Ca2+ levels. In activated HMC-1 cells, the phosphorylation of extra-signal response kinase (ERK 1/2) and c-jun N-terminal Kinase (JNK 1/2), but not p38 mitogen-activated protein kinase (p38 MAPK) were decreased by treatment of the cells with luteolin. Luteolin inhibited PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB degradation, and luciferase activity. Furthermore, luteolin suppressed the expression of TNF-alpha, IL-8, IL-6, GM-CSF, and COX-2 through a decrease in the intracellular Ca2+ levels, and also showed a suppression of the ERK 1/2, JNK 1/2, and NF-kappaB activation. These results indicated that luteolin from the flowers of Lonicera japonica exerted a regulatory effect on mast cell-mediated inflammatory diseases, such as RA, allergy disease and IBD.

Citing Articles

The therapeutic potential of Honeysuckle in cardiovascular disease: an anti-inflammatory intervention strategy.

Zhao Y, Zhang J, Lu F, Xu W, Ma Q, Hu J Am J Transl Res. 2025; 16(12):7262-7277.

PMID: 39822489 PMC: 11733370. DOI: 10.62347/NJMJ7853.

Boosting immunity: synergistic antiviral effects of luteolin, vitamin C, magnesium and zinc against SARS-CoV-2 3CLpro.

Ferreira J, Fadl S, Cardoso T, Andrade B, Melo T, Silva E Biosci Rep. 2024; 44(8).

PMID: 39045772 PMC: 11327220. DOI: 10.1042/BSR20240617.

Luteolin for neurodegenerative diseases: a review.

Jayawickreme D, Ekwosi C, Anand A, Andres-Mach M, Wlaz P, Socala K Pharmacol Rep. 2024; 76(4):644-664.

PMID: 38904713 PMC: 11294387. DOI: 10.1007/s43440-024-00610-8.

Lonicera japonica Thunb extract ameliorates lipopolysaccharide-induced acute lung injury associated with luteolin-mediated suppression of NF-κB signaling pathway.

Jia Q, Wen J, Yang Q, Liu S, Zhang J, Wang T J Inflamm (Lond). 2023; 20(1):44.

PMID: 38115057 PMC: 10729360. DOI: 10.1186/s12950-023-00372-9.

Anti-Proliferative Potential of Cynaroside and Orientin-In Silico (DYRK2) and In Vitro (U87 and Caco-2) Studies.

Pirvu L, Pintilie L, Albulescu A, Stefaniu A, Neagu G Int J Mol Sci. 2023; 24(23).

PMID: 38068880 PMC: 10705913. DOI: 10.3390/ijms242316555.

References

Kang O, Chae H, Choi J, Choi H, Park P, Cho S . Effects of the Schisandra fructus water extract on cytokine release from a human mast cell line. J Med Food. 2007; 9(4):480-6. DOI: 10.1089/jmf.2006.9.480. View

Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C . Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther. 2000; 296(1):181-7. View

Kang O, Lee G, Choi H, Park P, Chae H, Jeong S . Ethyl acetate extract from Angelica Dahuricae Radix inhibits lipopolysaccharide-induced production of nitric oxide, prostaglandin E2 and tumor necrosis factor-alphavia mitogen-activated protein kinases and nuclear factor-kappaB in macrophages. Pharmacol Res. 2007; 55(4):263-70. DOI: 10.1016/j.phrs.2006.12.001. View

Crossthwaite A, Hasan S, Williams R . Hydrogen peroxide-mediated phosphorylation of ERK1/2, Akt/PKB and JNK in cortical neurones: dependence on Ca(2+) and PI3-kinase. J Neurochem. 2002; 80(1):24-35. DOI: 10.1046/j.0022-3042.2001.00637.x. View

Manning A, Bell F, Rosenbloom C, Chosay J, Simmons C, Northrup J . NF-kappa B is activated during acute inflammation in vivo in association with elevated endothelial cell adhesion molecule gene expression and leukocyte recruitment. J Inflamm. 1995; 45(4):283-96. View

Barnes P, Adcock I . Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci. 1993; 14(12):436-41. DOI: 10.1016/0165-6147(93)90184-l. View

Arend W, Dayer J . Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum. 1995; 38(2):151-60. DOI: 10.1002/art.1780380202. View

Jeong H, Hong S, Lee D, Park J, Kim K, Kim H . Role of Ca(2+) on TNF-alpha and IL-6 secretion from RBL-2H3 mast cells. Cell Signal. 2002; 14(7):633-9. DOI: 10.1016/s0898-6568(02)00005-0. View

Kim M, Lim W, Park R, Shin T, Yoo Y, Hong S . Involvement of mitogen-activated protein kinase and NF-kappaB activation in Ca2+-induced IL-8 production in human mast cells. Cytokine. 2005; 32(5):226-33. DOI: 10.1016/j.cyto.2005.10.001. View

10.

Royer B, Varadaradjalou S, Saas P, Gabiot A, Kantelip B, Feger F . Autocrine regulation of cord blood-derived human mast cell activation by IL-10. J Allergy Clin Immunol. 2001; 108(1):80-6. DOI: 10.1067/mai.2001.115753. View

11.

Newton R, Kuitert L, Bergmann M, Adcock I, Barnes P . Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta. Biochem Biophys Res Commun. 1997; 237(1):28-32. DOI: 10.1006/bbrc.1997.7064. View

12.

Ershler W, Keller E . Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000; 51:245-70. DOI: 10.1146/annurev.med.51.1.245. View

13.

Rasmussen H, GOODMAN D . Relationships between calcium and cyclic nucleotides in cell activation. Physiol Rev. 1977; 57(3):421-509. DOI: 10.1152/physrev.1977.57.3.421. View

14.

Lee F, HAGLER J, Chen Z, Maniatis T . Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell. 1997; 88(2):213-22. DOI: 10.1016/s0092-8674(00)81842-5. View

15.

Kim S, Jeong H, Choi I, Lee K, Park R, Hong S . Cyclooxygenase-2 inhibitor SC-236 [4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide] suppresses nuclear factor-kappaB activation and phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated.... J Pharmacol Exp Ther. 2005; 314(1):27-34. DOI: 10.1124/jpet.104.082792. View

16.

Foreman J . Mast cells and the actions of flavonoids. J Allergy Clin Immunol. 1984; 73(6):769-74. DOI: 10.1016/0091-6749(84)90446-9. View

17.

Pastore S, Fanales-Belasio E, Albanesi C, Chinni L, Giannetti A, Girolomoni G . Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin. J Clin Invest. 1997; 99(12):3009-17. PMC: 508153. DOI: 10.1172/JCI119496. View

18.

Azzolina A, Bongiovanni A, Lampiasi N . Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochim Biophys Acta. 2003; 1643(1-3):75-83. DOI: 10.1016/j.bbamcr.2003.09.003. View

19.

Takizawa H, Ohtoshi T, Kikutani T, Okazaki H, Akiyama N, Sato M . Histamine activates bronchial epithelial cells to release inflammatory cytokines in vitro. Int Arch Allergy Immunol. 1995; 108(3):260-7. DOI: 10.1159/000237162. View

20.

Chen C, Peng W, Tsai K, Hsu S . Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 2007; 81(23-24):1602-14. PMC: 7094354. DOI: 10.1016/j.lfs.2007.09.028. View