title: 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.
abstract: 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 microg/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 us 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-naphthalene-2-carbaldehyde with an IC(50) of 2.4 and 2.0 microM for IL-6 inhibition and an IC(50) of 15.6 and 7.0 microM 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.
authors.affiliation: Screening and Biotechnology, Department of Pharmacology, Piramal Life Sciences Limited, 1 Nirlon Complex, Mumbai 400063, India. asha.almeida@piramal.com
authors.forename: Asha
authors.initials: A
authors.lastname: Kulkarni-Almeida
authors.forename: Ashish
authors.initials: A
authors.lastname: Suthar
authors.forename: Hitesh
authors.initials: H
authors.lastname: Goswami
authors.forename: Ram
authors.initials: R
authors.lastname: Vishwakarma
authors.forename: Vijay Singh
authors.initials: VS
authors.lastname: Chauhan
authors.forename: Arun
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Somesh
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000328:Adult; D002460:Cell Line; D028162:Heliotropium / Q000737:chemistry*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
chemical_list: D008070:Lipopolysaccharides; D009281:Naphthalenes; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C534689:4,7,8-trimethoxy-naphthalene-2-carboxylic acid; C534690:6-hydroxy-5,7-dimethoxy-naphthalene-2-carbaldehyde