Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice.

Abstract

Clematis mandshurica Ruprecht root has been used in Asia as a traditional anti-inflammatory, analgesic, and antitumor agent. Its main active component is hederagenin, a naturally occurring triterpene, and in this study, we examined the anti-inflammatory effects of hederagenin in lipopolysaccharide-stimulated RAW 264.7 cells using an enzyme-linked immunosorbent assay, Western blot, and RT-PCR. In addition, its effects on acute inflammation in vivo were observed using a carrageenan-induced mouse hind paw edema assay. Furthermore, the changes on the histopathology and histomorphometry of hind paw skins were examined using carrageenan-treated mice. Treatment with hederagenin (10, 30 and 100μM) resulted in inhibited levels of protein expression of lipopolysaccharide-stimulated iNOS, COX-2, and NF-κB as well as production of NO, PGE2, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide. Consistent with these results, hederagenin also dose-dependently reduced the lipopolysaccharide-induced mRNA levels of iNOS and COX-2, and of the above-mentioned cytokines. Interestingly, results of the carrageenan-induced mouse hind paw edema assay showed an anti-edema effect of hederagenin. Furthermore, hederagenin (30mg/kg) inhibited the carrageenan-induced increases in skin thicknesses, infiltrated inflammatory cells, and mast cell degranulation. These results suggest that hederagenin may possess anti-inflammatory activities.

• Authors: Chul Won Lee, Sang Mi Park, Rongjie Zhao, Chu Lee, Wonjoo Chun, Yonghae Son, Sung Hun Kim, Ji Yun Jung, Kyung Hwan Jegal, Il Je Cho, Sae Kwang Ku, Young Woo Kim, Seong A Ju, Sang Chan Kim, Won G An
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 29 Issue 2 Pg. 528-537 (Dec 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 26481049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Lipopolysaccharides
• Oleanolic Acid
• Carrageenan
• hederagenin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Carrageenan
• Clematis (chemistry)
• Cytokines (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Edema (chemically induced, prevention & control)
• Foot (pathology)
• Inflammation (chemically induced, prevention & control)
• Lipopolysaccharides (pharmacology)
• Mice
• Oleanolic Acid (analogs & derivatives, pharmacology)
• Plant Roots (chemistry)
• RAW 264.7 Cells
• Skin (pathology)