Inhibition of LPS-induced production of inflammatory factors in the macrophages by mono-carbonyl analogues of curcumin

J Cell Mol Med. 2009 Sep;13(9B):3370-9. doi: 10.1111/j.1582-4934.2009.00711.x. Epub 2009 Feb 20.


Curcumin (diferuloylmethane) is an orange-yellow compound from turmeric (Curcuma longa), a spice found in curry powder. Traditionally known for its anti-inflammatory effects, curcumin has established itself in the last two decades to be a potent immunomodulatory agent that can regulate the activation of a variety of immunocytes and the expression of inflammatory factors. Considering that the beta-diketone moiety of curcumin may result in its instability and poor metabolic property, we previously designed a series of mono-carbonyl analogues of curcumin with enhanced stability by deleting this moiety. These compounds demonstrate improved pharmacokinetic profiles both in vitro and in vivo. In this study, we reported a total of 44 mono-carbonyl analogues, which have been evaluated for the inhibitory activities against LPS-induced TNF-alpha and IL-6 release in the macrophages. Based on the screening results of these analogues, five active compounds A01, A03, A13, B18 and C22 were investigated to inhibit TNF-alpha and IL-6 release in a dose-dependent manner, three of which further demonstrated inhibitory effects on LPS-induced TNF-alpha, IL-1beta, IL-6, MCP-1, COX-2, PGES, iNOS and p65 NF-kappaB mRNA production. The results indicated that these mono-carbonyl analogues may possess anti-inflammatory activities similar to curcumin despite the absence of the beta-diketone. These mono-carbonyl analogues may be a favourable alternative for the development of curcumin-based anti-inflammatory drugs both pharmacokinetically and pharmacologically. We further examined the biological properties of A13, the only hydrosoluble analogue when combined with hydrochloric acid. The results showed a dose-dependent inhibition of LPS-induced cytokine production. These data further indicated that compound A13 may be explored as a promising anti-inflammatory molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon / chemistry*
  • Curcuma
  • Curcumin / chemistry*
  • Inflammation
  • Interleukin-6 / metabolism
  • Ketones / metabolism
  • Lipopolysaccharides / metabolism*
  • Macrophages / metabolism
  • Mice
  • Models, Chemical
  • Plant Extracts / pharmacology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-6
  • Ketones
  • Lipopolysaccharides
  • Plant Extracts
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Carbon
  • Curcumin