Immunosuppressive properties of flavonoids isolated from Boerhaavia diffusa Linn.
Plant extracts have been widely evaluated for possible immunomodulatory properties. We have earlier reported that ethanolic extract of Boerhaavia diffusa root, a plant used in Indian traditional medicine, has significant immunomodulatory potential. B. diffusa hexane, chloroform and ethanol extracts, and two pure compounds Bd-I (eupalitin-3-O-beta-D-galactopyranoside) and Bd-II (eupalitin) were evaluated in vitro for their effect on T cell mitogen (phytohemagglutinin; PHA) stimulated proliferation of human peripheral blood mononuclear cell (PBMC), mixed lymphocyte culture, lipopolysaccharide (LPS) stimulated nitric oxide production by RAW 264.7, PHA and LPS induced IL-2 and TNF-alpha production, in human PBMCs, superoxide production in neutrophils, human natural killer (NK) cell cytotoxicity and nuclear translocation of nuclear factor-(kappa)B and AP-1 in PHA stimulated PBMCs. The chloroform and ethanol extracts inhibited PHA stimulated proliferation of peripheral blood mononuclear cells, two-way MLR, NK cell cytotoxicity as well as LPS induced NO production by RAW 264.7; the hexane extract showed no activity. Bd-I purified from the ethanolic extract at equivalent dose, inhibited PHA-stimulated proliferation of peripheral blood mononuclear cells, two-way MLR and NK cell cytotoxicity as well as LPS induced NO production by RAW 264.7 equally or more effectively than the parent ethanolic extract. Bd-I inhibited production of PHA stimulated IL-2 at the protein and mRNA transcript levels and LPS stimulated TNF-alpha production in human PBMCs; it also blocked the activation of DNA binding of nuclear factor-(kappa)B and AP-1, two major transcription factors centrally involved in expression of the IL-2 and IL-2R gene, which are necessary for T cell activation and proliferation. Our results report selective immunosuppressive activity of B. diffusa leaf extracts and that this activity lies in eupalitin-3-O-beta-D-galactopyranoside (Bd-I) isolated and purified from the ethnaolic extract. Thus, Bd-I could be a candidate for development as an immunosuppressive agent.
Pandey
Rahul
R
Department of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow 226 014, India.
Maurya
Rakesh
R
Singh
Geetu
G
Sathiamoorthy
B
B
Naik
Sita
S
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D039281:Nyctaginaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D016897:Respiratory Burst / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
D005419:Flavonoids; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D009569:Nitric Oxide