Protective role of 14-deoxy-11,12-didehydroandrographolide, a noncytotoxic analogue of andrographolide, in allergic airway inflammation.

Abstract

Our group recently reported novel anti-inflammatory effects of andrographolide (2), a bioactive molecule isolated from Andrographis paniculata, in a mouse asthma model. However, 2 has been shown to possess cytotoxic activity. 14-Deoxy-11,12-didehydroandrographolide (1) is an analogue of 2 that can be isolated from A. paniculata. We hypothesized that 1 retains the anti-inflammatory effects for asthma but is devoid of cytotoxicity. In contrast to 2, 1 did not elicit any cytotoxic activity in A549 and BEAS-2B human lung epithelial cells and rat basophilic leukemia (RBL)-2H3 cells using a MTS assay. Compound 1 dose-dependently inhibited ovalbumin (OVA)-induced increases in total 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. Compound 1 attenuated OVA-induced airway eosinophilia, mucus production, mast cell degranulation, pro-inflammatory biomarker expression in lung tissues, and airway hyper-responsiveness. This substance also blocked p65 nuclear translocation and DNA-binding activity in the OVA-challenged lung and in TNF-α-stimulated human lung epithelial cells. The present findings reveal for the first time that 1 retains the anti-inflammatory activities of 2 for asthma probably through the inhibition of NF-κB. 14-Deoxy-11,12-didehydroandrographolide (1) may be considered as a safer analogue of 2 for the potential treatment of asthma.

• Authors: Shou-Ping Guan, Li-Ren Kong, Chang Cheng, Jonathan C W Lim, W S Fred Wong
• Journal: Journal of natural products (J Nat Prod) Vol. 74 Issue 6 Pg. 1484-90 (Jun 24 2011) ISSN: 1520-6025 [Electronic] United States
• PMID: 21598983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-deoxy-11,12-didehydroandrographolide
• Anti-Inflammatory Agents
• Diterpenes
• NF-kappa B
• Tumor Necrosis Factor-alpha
• andrographolide
• Ovalbumin

Topics

• Andrographis (chemistry)
• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Asthma (chemically induced, drug therapy)
• Disease Models, Animal
• Diterpenes (chemistry, pharmacology)
• Humans
• Lung (drug effects, metabolism)
• Mice
• NF-kappa B (antagonists & inhibitors)
• Ovalbumin (antagonists & inhibitors)
• Rats
• Tumor Necrosis Factor-alpha (pharmacology)