Stem-bark of Terminalia arjuna attenuates human monocytic (THP-1) and aortic endothelial cell activation

作者：Kokkiripati Praveen K; Kamsala Ratnam V; Bashyam Leena; Manthapuram Nalini; Bitla Prasanth; Peddada Vidyadhari; Raghavendra Agepati S; Tetali Sarada D^*

来源：Journal of Ethnopharmacology, 2013, 146(2): 456-464.

DOI：10.1016/j.jep.2012.12.050

• Endothelial cells
• LPS
• Monocytes
• Terminalia arjuna stem bark
• TNF-alpha
• VCAM-1

Ethnopharmacological relevance: Terminalia arjuna - stem bark extract is traditionally used as cardiotonic in Ayurvedic medicine. %26lt;br%26gt;Aim of the study: The present study was aimed to evaluate the molecular basis for cardioprotective potential of Terminalia arjuna (TA) stem bark, using cell cultures of human monocytic (THP-1) and human aortic endothelial cells (HAECs). %26lt;br%26gt;Materials and methods: Inhibitory effect of alcoholic (TAAE) and aqueous (TAWE) extracts of TA-stem bark was assessed on human 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LpL) and lipid peroxidation in rat (wistar) liver and heart homogenates. The patterns of H2O2 induced reactive oxygen species (ROS) generation were observed by confocal microscopy. The activities of antioxidant enzymes and reducing power of the cells were measured in a microplate reader. Gene transcripts of proinflammatory markers in THP-1 and HAECs were assayed by real time PCR and levels of inflammatory protein markers by ELISA or flow cytometry. Phytochemical analyses of TAAE and TAWE were done using liquid chromatography, coupled to mass spectrometry (LC-MS). %26lt;br%26gt;Results: TAAE and TAWE inhibited the lipid peroxidation and HMG-CoA reductase but had no effect on LpL. Both the extracts attenuated H2O2 mediated ROS generation in THP-1 cells by promoting catalase (CAT), glutathione peroxidase (GPx) activities, and by sustaining cellular reducing power. TAAE was highly effective in attenuating proinflammatory gene transcripts in THP-1 cells and HAECs, whereas the response to TAWE depended on the type of transcript and cell type. Both extracts decreased the levels of typical inflammatory marker proteins, viz. LPS induced tumor necrosis factor (TNF)-alpha secreted by THP-1 cells and TNF-alpha induced cell surface adhesion molecules on HAECs, namely vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Phytochemical analyses indicated the richness in phenolic compounds and terpenes of TAAE and TAWE, while revealing variability in their metabolite profile. %26lt;br%26gt;Conclusion: Our study scientifically validates the antioxidative and antiinflammatory properties of Terminalia arjuna stem bark. The marked effects on cultured human monocytic and aortic endothelial cells (HAEC) provide the biochemical and molecular basis for therapeutic potential of TA-stem bark against cardiovascular diseases (CVD).

• 出版日期2013-3-27