Effects of andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide in obstructive respiratory disease mouse models

Abstract

Andrographolide and DDAG are biologically active compounds. Unlike andrographolide, DDAG are not cytotoxic to A549, BEAS-2B and RBL-2H3 cells. DDAG dose-dependently inhibited OVA-induced increases in total cell counts and eosinophil counts, IL-4, IL-5, and IL-13 levels in lavage fluid and serum OVA-specific IgE level in a mouse asthma model. Additionally, DDAG attenuated mucus production, mast cell degranulation, pro-inflammatory biomarker expression in lung tissues and AHR in mice. DDAG also blocked p65 nuclear translocation and DNA-binding activity in the OVA-challenged lung and in TNF-a -stimulated cells. Andrographolide suppressed cigarette smoke-induced increases in BAL fluid cell counts, levels of IL-1?, MCP-1, IP-10 and KC and levels of oxidative biomarkers but promoted GPx and GR activities. In BEAS-2B cells, andrographolide markedly increased nuclear Nrf2 accumulation, promoted binding to ARE and total cellular glutathione level in response to CSE. Andrographolide up-regulated GCLC, GCLM, GPx, GR and HO-1 in BEAS-2B cells in response to CSE.