PROGRAMME SCIENTIFIQUE - Oxygen Club of California

OP15
A nutrigenomic approach to study the effect of herbal polyphenols on inflammatory
transcriptome in coronary artery disease.
Dhawan V, Malik N, Bahl A, Kaul D.
Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.E.mail:veenad2001@yahoo.com
Background: Atherosclerosis has a multifactorial etiology and inflammation plays a pivotal role in the
process of atherogenesis. In traditional Ayurvedic system of medicine, certain herbal preparations have
been identified to have beneficial effects on cardiovascular patho-physiology. However, in the context of
modern medicine it becomes imperative to have scientific validation of the claim made in Ayurvedic
medicine. Terminalia arjuna is an important cardiotonic plant described in the ancient Indian medical
science. Evidence in literature indicates that it has potent hypolipidemic, antioxidative and antiinflammatory
properties, but scientific validation and proof for the same is lacking. Therefore, the present
study was conducted to investigate the effect of this medicinal herb on expression of inflammatory genes
in subjects with coronary artery disease.
Methods : In the present study 40 subjects with angiographically proven coronary artery disease (Group
I) and 40 age and sex-matched healthy controls (Group II) were enrolled at special cardiology clinic in
PGIMER. The polyphenols were extracted from the bark of Terminalia arjuna (TA) and were isolated
using standard methods. The isolated polyphenols were further purified and fractionated by HPLC. The
peak fractions (Fraction I to V) were collected and dialysed against normal saline and subsequently used
for culture experiments. Time and dose-dependent studies were carried out to evaluate the effects of the
bark extract of Terminalia arjuna (TAE) on cell viability, cell proliferation and on LPS-induced
expression of inflammatory genes - IL-18, COX-2, RAGE and MMP-2 in PBMCs of study subjects by
semi-quantitative RT-PCR and Western blot analysis. Further, PBMCs from the study subjects were
cultured in presence of HPLC purified sub-fractions of the bark extract of Terminalia arjuna (0-
150ug/ml; 0 = control).
Results: Trypan blue exclusion and BrdU cell proliferation assay showed that upto 200 µg of bark
extract/ml/10 6 cells had no cytotoxic effects as it did not affect the viability and proliferation of PBMCs
upto 48 hours. Exposure of mononuclear cells to both TAE and HPLC isolated Fractions II and IV
revealed a dose-dependent down regulation of genes coding for IL-18, COX-2, MMP-2 and RAGE both
at the transcriptional and translational level.
Conclusion : Our observations clearly indicate that this medicinal herb attenuates the expression of
inflammatory genes and thereby, possesses anti inflammatory properties and does not demonstrate
cytotoxic properties Our data validates that this medicinal herb has cardioprotective properties by virtue
of its inflammatory potential and provides scientific basis for its use in future clinical trials for the
prevention and management of CAD.