Inhibitory effects of kaurenoic acid from Aralia continentalis on LPS-induced inflammatory response in RAW264.7 macrophages.

Abstract

This study investigates the anti-inflammatory effects of a diterpenoid, kaurenoic acid, isolated from the root of Aralia continentalis (Araliaceae). To determine its anti-inflammatory effects, LPS-induced RAW264.7 macrophages were treated with different concentrations of kaurenoic acid and carrageenan-induced paw edema mice model was used in vivo. Kaurenoic acid (ent-kaur-16-en-19-oic acid) dose-dependently inhibited nitric oxide (NO) production, prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression at micromolar concentrations in LPS-induced RAW264.7 macrophages with IC(50) (the half maximal inhibitory concentration) values of 51.73 (±2.42) μM and 106.09 (±0.27) μM in NO production and PGE(2) release, respectively. Kaurenoic acid also dose-dependently inhibited LPS-induced activation of NF-κB as assayed by electrophorectic mobility shift assay (EMSA) and it almost abolished NF-κB DNA binding affinity at 100μM. Furthermore, the in vivo anti-inflammatory effect of kaurenoic acid was examined in a carrageenan-induced paw edema model. Eight ICR mice in each group were injected with carrageenan and observed hourly, compared with the control group. Kaurenoic acid dose-dependently reduced paw swelling up to 34.4% at 5h after induction, demonstrating inhibition in an acute inflammation model. Taken together, our data suggest that kaurenoic acid, a major diterpenoid from the root of A. continentalis shows anti-inflammatory activity and the inhibition of iNOS and COX-2 expression might be one of the mechanisms responsible for its anti-inflammatory properties.

• Authors: Ran Joo Choi, Eun Myoung Shin, Hyun Ah Jung, Jae Sue Choi, Yeong Shik Kim
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 18 Issue 8-9 Pg. 677-82 (Jun 15 2011) ISSN: 1618-095X [Electronic] Germany
• PMID: 21211951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier GmbH. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Diterpenes
• Lipopolysaccharides
• NF-kappa B
• Plant Extracts
• Nitric Oxide
• kaurenoic acid
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Cyclooxygenase 2
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (isolation & purification, pharmacology)
• Aralia (chemistry)
• Cyclooxygenase 2 (biosynthesis)
• Dinoprostone (antagonists & inhibitors, biosynthesis)
• Diterpenes (isolation & purification, pharmacology)
• Inflammation (chemically induced, drug therapy, metabolism)
• Lipopolysaccharides (antagonists & inhibitors)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• Nitric Oxide (antagonists & inhibitors, biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors, biosynthesis)
• Phytotherapy
• Plant Extracts (isolation & purification, pharmacology)
• Plant Roots (chemistry)