PMID- 21843619 OWN - NLM STAT- MEDLINE DCOM- 20120214 LR - 20131121 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 137 IP - 3 DP - 2011 Oct 11 TI - Ethyl gallate isolated from Pistacia integerrima Linn. inhibits cell adhesion molecules by blocking AP-1 transcription factor. PG - 1345-52 LID - 10.1016/j.jep.2011.07.068 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Galls from Pistacia integerrima Linn. (kakadshringhi) have been used as therapeutic agent for various inflammatory diseases in Indian system of traditional medicine. However, the active constituents underlying the medicinal properties of the Pistacia integerrima Linn. have not been thoroughly investigated yet. AIM OF THE STUDY: Deregulated expression of cell adhesion molecules (CAMs) on vascular endothelium aggravates the inflammatory condition in various chronic diseases. In this work, we aimed to identify the active constituent from leaf gall of Pistacia integerrima Linn. using CAMs expression assay in activity guided purification, followed by determining the molecular mechanism of action. MATERIAL AND METHODS: Cell based ELISA for LPS induced CAMs expression in human vein endothelial cells (HUVECs) was used for the activity guided isolation form Pistacia galls followed by structural determination of active constituent using IR, MS and NMR spectroscopy. Mechanism of action of the active constituent was investigated by western blot, RT-PCR and EMSA experiments. RESULTS: In our study, ethyl gallate (EG) was identified as the active constituent of Pistacia integerrima Linn. for mediating its anti-inflammatory activity. It significantly attenuated LPS induced ICAM-1 and VCAM-1 at the protein and mRNA levels. At a functional level, it inhibited the adhesion of neutrophils to LPS activated endothelium. To identify its mechanism of action, we demonstrated that EG inhibited LPS induced cell adhesion molecules expression by blocking AP-1 transcription factor without affecting nuclear transcription factor-kappaB (NF-kappaB). CONCLUSION: Our results suggest that EG could be useful as a lead molecule for developing therapeutic agent for various inflammatory diseases. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Mehla, Kamiya AU - Mehla K AD - Molecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India. FAU - Balwani, Sakshi AU - Balwani S FAU - Kulshreshtha, Ankur AU - Kulshreshtha A FAU - Nandi, Debkumar AU - Nandi D FAU - Jaisankar, Parasuraman AU - Jaisankar P FAU - Ghosh, Balaram AU - Ghosh B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110805 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Plant Extracts) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 235I6UDD3L (ethyl gallate) RN - 632XD903SP (Gallic Acid) SB - IM MH - Anti-Inflammatory Agents/isolation & purification/*pharmacology MH - Blotting, Western MH - Cell Adhesion/*drug effects MH - Cells, Cultured MH - Chemical Fractionation MH - Chromatography, High Pressure Liquid MH - Chromatography, Thin Layer MH - Coculture Techniques MH - Dose-Response Relationship, Drug MH - Electrophoretic Mobility Shift Assay MH - Enzyme-Linked Immunosorbent Assay MH - Gallic Acid/*analogs & derivatives/isolation & purification/pharmacology MH - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism MH - Intercellular Adhesion Molecule-1/genetics/*metabolism MH - Magnetic Resonance Spectroscopy MH - Mass Spectrometry MH - Neutrophils/drug effects/metabolism MH - *Pistacia/chemistry MH - Plant Extracts/isolation & purification/*pharmacology MH - Plant Leaves MH - Plant Tumors MH - Plants, Medicinal MH - RNA, Messenger/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Time Factors MH - Transcription Factor AP-1/*antagonists & inhibitors/metabolism MH - Vascular Cell Adhesion Molecule-1/genetics/*metabolism EDAT- 2011/08/17 06:00 MHDA- 2012/02/15 06:00 CRDT- 2011/08/17 06:00 PHST- 2011/02/08 00:00 [received] PHST- 2011/06/10 00:00 [revised] PHST- 2011/07/30 00:00 [accepted] PHST- 2011/08/17 06:00 [entrez] PHST- 2011/08/17 06:00 [pubmed] PHST- 2012/02/15 06:00 [medline] AID - S0378-8741(11)00562-9 [pii] AID - 10.1016/j.jep.2011.07.068 [doi] PST - ppublish SO - J Ethnopharmacol. 2011 Oct 11;137(3):1345-52. doi: 10.1016/j.jep.2011.07.068. Epub 2011 Aug 5.