PMID- 20558233 OWN - NLM STAT- MEDLINE DCOM- 20101220 LR - 20220317 IS - 1638-6183 (Electronic) IS - 0300-9084 (Linking) VI - 92 IP - 9 DP - 2010 Sep TI - beta-sitosterol among other secondary metabolites of Piper galeatum shows inhibition of TNFalpha-induced cell adhesion molecule expression on human endothelial cells. PG - 1213-21 LID - 10.1016/j.biochi.2010.06.005 [doi] AB - A phytochemical investigation of the stems of Piper galeatum yielded one novel amide, 1-(3'-hydroxy-5'-methoxycinnamoyl)-piperidine (5) along with four known compounds, i.e. beta-sitosterol (1), cyclostachine-A (2), piperine (3) and piperolein-B (4). The structures of all the five compounds, isolated for the first time from this plant were unambiguously established on the basis of their detailed spectral analysis. The structure of cyclostachine-A (2) was confirmed by X-ray crystallographic studies and structures of known compounds were confirmed by comparison of their physical and/or chemical data with those reported in the literature, which were in complete agreement. Additionally, the crude extracts as well as the isolated pure compounds were screened for their activity to inhibit TNFalpha (tumour necrosis factor-alpha)- induced expression of cell adhesion molecule ICAM-1 (intercellular adhesion molecule-1) on the surface of human umbilical vein endothelial cells (HUVECs). Among all, beta-sitosterol (1) was found to be the most active compound, which was taken for further studies. beta-sitosterol also significantly inhibited the TNFalpha-induced expression of VCAM-1 and E-selectin, which also play key role in various inflammatory diseases. The functional correlation of cell adhesion molecules inhibition was assessed by cell adhesion assay using human neutrophils. We found that beta-sitosterol significantly blocks the adhesion of neutrophils to endothelial monolayer. To elucidate the molecular mechanism of inhibition of cell adhesion molecules, we investigated the status of nuclear transcription factor-kappaB (NF-kappaB) and were able to establish that beta-sitosterol significantly blocked the TNFalpha-induced activation of NF-kappaB. CI - Copyright (c) 2010 Elsevier Masson SAS. All rights reserved. FAU - Gupta, Pankaj AU - Gupta P AD - Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi-110 007, India. FAU - Balwani, Sakshi AU - Balwani S FAU - Kumar, Sarvesh AU - Kumar S FAU - Aggarwal, Neha AU - Aggarwal N FAU - Rossi, Miriam AU - Rossi M FAU - Paumier, Sarah AU - Paumier S FAU - Caruso, Francesco AU - Caruso F FAU - Bovicelli, Paolo AU - Bovicelli P FAU - Saso, Luciano AU - Saso L FAU - DePass, Anthony L AU - DePass AL FAU - Prasad, Ashok K AU - Prasad AK FAU - Parmar, Virinder S AU - Parmar VS FAU - Ghosh, Balaram AU - Ghosh B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100615 PL - France TA - Biochimie JT - Biochimie JID - 1264604 RN - 0 (Cell Adhesion Molecules) RN - 0 (E-Selectin) RN - 0 (Plant Extracts) RN - 0 (Sitosterols) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Cell Adhesion/drug effects MH - Cell Adhesion Molecules/*metabolism MH - Cells, Cultured MH - E-Selectin/metabolism MH - Endothelial Cells/*drug effects/*metabolism MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Neutrophils/cytology/drug effects MH - Piper/*chemistry MH - Plant Extracts/*pharmacology MH - Sitosterols/*pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Vascular Cell Adhesion Molecule-1/metabolism EDAT- 2010/06/19 06:00 MHDA- 2010/12/21 06:00 CRDT- 2010/06/19 06:00 PHST- 2010/02/26 00:00 [received] PHST- 2010/06/04 00:00 [accepted] PHST- 2010/06/19 06:00 [entrez] PHST- 2010/06/19 06:00 [pubmed] PHST- 2010/12/21 06:00 [medline] AID - S0300-9084(10)00219-1 [pii] AID - 10.1016/j.biochi.2010.06.005 [doi] PST - ppublish SO - Biochimie. 2010 Sep;92(9):1213-21. doi: 10.1016/j.biochi.2010.06.005. Epub 2010 Jun 15.