Open AccessInhibition of LPS‐induced production of inflammatory factors in the macrophages by mono‐carbonyl analogues of curcumin
Author(s) -
Liang Guang,
Zhou Huiping,
Wang Yi,
Gurley Emily C.,
Feng Biao,
Chen Li,
Xiao Jian,
Yang Shulin,
Li Xiaokun
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00711.x
Subject(s) - curcumin , chemistry , moiety , curcuma , in vitro , in vivo , pharmacology , anti inflammatory , biochemistry , tumor necrosis factor alpha , stereochemistry , biology , immunology , medicine , traditional medicine , microbiology and biotechnology
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 β‐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‐α 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‐α and IL‐6 release in a dose‐dependent manner, three of which further demonstrated inhibitory effects on LPS‐induced TNF‐α, IL‐1β, IL‐6, MCP‐1, COX‐2, PGES, iNOS and p65 NF‐κB mRNA production. The results indicated that these mono‐carbonyl analogues may possess anti‐inflammatory activities similar to curcumin despite the absence of the β‐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.