beta-sitosterol among other secondary metabolites of Piper galeatum shows inhibition of TNFalpha-induced cell adhesion molecule expression on human endothelial cells.
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.
Gupta
Pankaj
P
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi-110 007, India.
Balwani
Sakshi
S
Kumar
Sarvesh
S
Aggarwal
Neha
N
Rossi
Miriam
M
Paumier
Sarah
S
Caruso
Francesco
F
Bovicelli
Paolo
P
Saso
Luciano
L
DePass
Anthony L
AL
Prasad
Ashok K
AK
Parmar
Virinder S
VS
Ghosh
Balaram
B
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D012855:Sitosterols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D010936:Plant Extracts; D012855:Sitosterols; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1