Novel leads from Heliotropium ovalifolium, 4,7,8-trimethoxy-naphthalene-2-carboxylic acid and 6-hydroxy-5,7-dimethoxy-naphthalene-2-carbaldehyde show specific IL-6 inhibitory activity in THP-1 cells and primary human monocytes

作者：Kulkarni Almelda Asha^*; Suthar Ashish; Goswami Hitesh; Vishwakarma Ram; Chauhan Vijay Singh; Balakrishnan Arun; Sharma Somesh

来源：Phytomedicine, 2008, 15(12): 1079-1086.

DOI：10.1016/j.phymed.2008.04.013

• Il-6
• Heliotropium ovalifolium
• THP-1
• Human monocytes
• Inflammatory disorders

From our screening program, we identified the anti-inflammatory effects of the extracts of Heliotropium ovalifolium in its ability to inhibit specific cytokines. The H. ovalifolium extract was found to be moderately active with an IC(50) equaling 10 mu g/ml for inhibition of interleukin-6 (IL-6) in a human monocytic cell line. Interleukin-6 is a pleiotropic cytokine with implications in the regulation of the immune response, inflammation and hematopoiesis. This prompted LIS to examine and identify the active molecules that are responsible for the bioactivity in THP-1 cells. Bioassay guided fractionation identified two compounds 4,7,8-trimethoxy-naphthalene-2-carboxylic acid and 6-hydroxy-5,7-dimethoxy-nphthalene-2-carbaldehyde with an IC(50) of 2.4 and 2.0 mu M for IL-6 inhibition and an IC(50) of 15.6 and 7.0 mu M for tumor necrosis factor-alpha (TNF-alpha) inhibition in THP-1 cells. The protein expression data were Supported by the inhibitory effect on mRNA gene expression. The compounds isolated from H. ovalifolium were also non-toxic in human peripheral blood monocytes from normal donors and the activity profile was similar to that obtained on THP-1 cells. Thus, we believe that these scaffolds may be of interest to develop leads for treating rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease and other inflammatory disorders. However, more detailed investigations need to be carried out to explain the efficacy of these compounds as drugs.

• 出版日期2008-12