Modulation of gene expression by Polyalthia longifolia in postmenopausal women with coronary artery disease: an in vitro study.
Chronic underlying inflammation is involved in the pathophysiology of coronary artery disease (CAD). Polyalthia longifolia var. pendula bark extract (PLE) is known to exhibit anti-inflammatory activity and has high content of phytosteroids. Since phytosteroids mimic estrogen structurally, we postulated that PLE may provide protection in postmenopausal women against CAD. Thus the effect of PLE has been explored on expression of estrogen receptors (ERalpha and ERbeta) and inflammatory inducible nitric oxide synthase (iNOS) genes in vitro in peripheral blood mononuclear cells (PBMCs) obtained from postmenopausal women. A total of 20 postmenopausal women were included in the present study. Group I (N = 10) included women with angiographically proven CAD, and group II (N = 10) is composed of equal number of age-matched healthy postmenopausal females as controls. Significantly low levels of serum 17-beta estradiol were observed in subjects of group I as compared to group II (p < 0.01). A marked increase in L: -citrulline levels (p > 0.05) and significantly augmented levels of reactive nitrogen intermediates (p < 0.05) were observed in group I subjects. PLE significantly attenuated PMA-induced expression of both ERalpha and ERbeta receptors and inflammatory iNOS gene in vitro in a dose- and time-dependent manner and had an additive effect on these genes when compared with tamoxifen. Ours is the first report to demonstrate that PLE contains certain bioactive principles, which possess anti-inflammatory and estrogenic properties, and thereby hold the promise to be screened for their anti-atherogenic potential in experimental animals to favorably alter several other markers of cardiovascular risk.
Mittal
Anupam
A
Department of Experimental Medicine & Biotechnology, Research Block 'B', Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India.
Mahajan
Nitin
N
Vijayvergiya
Rajesh
R
Dhawan
Veena
V
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D002956:Citrulline / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007194:India; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010865:Pilot Projects; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology*; D031044:Polyalthia; D017698:Postmenopause; D026361:Reactive Nitrogen Species / Q000097:blood; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010936:Plant Extracts; D026361:Reactive Nitrogen Species; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D002956:Citrulline; D004958:Estradiol; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II