Effect of curcumin (Curcuma longa extract) on LPS-induced acute lung injury is mediated by the activation of AMPK
Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5′ adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury.
Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice.
Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium2+/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment.
These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.
KeywordsAMPK CaMKK Curcumin LPS Macrophage
This study was supported by a grant (CRI13021-1) from the Chonnam National University Hospital Research Institute of Clinical Medicine.
Compliance with ethical standards
Conflict of interest
There is no conflict of interest.
- 10.Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009;14:141–53.Google Scholar
- 16.Bae HB, Li M, Son JK, Seo CS, Chung SH, Kim SJ, Jeong CW, Lee HG, Kim W, Park HC, Kwak SH. Sauchinone, a lignan from Saururus chinensis, reduces tumor necrosis factor-alpha production through the inhibition of c-raf/MEK1/2/ERK 1/2 pathway activation. Int Immunopharmacol. 2010;10:1022–8.Google Scholar
- 17.Han HJ, Li M, Son JK, Seo CS, Song SW, Kwak SH, Bae HB. Sauchinone, a lignan from Saururus chinensis, attenuates neutrophil pro-inflammatory activity and acute lung injury. Int Immunopharmacol. 2013;17:471–7.Google Scholar
- 31.Misra J, Chanda D, Kim DK, Li T, Koo SH, Back SH, Chiang JY, Choi HS. Curcumin differentially regulates endoplasmic reticulum stress through transcriptional corepressor SMILE (small heterodimer partner-interacting leucine zipper protein)-mediated inhibition of CREBH (cAMP responsive element-binding protein H). J Biol Chem. 2011;286:41972–84.PubMedCentralCrossRefPubMedGoogle Scholar
- 38.Greenberger MJ, Strieter RM, Kunkel SL, Danforth JM, Laichalk LL, McGillicuddy DC, Standiford TJ. Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis. 1996;173:159–65.Google Scholar