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

• DOI: 10.1016/j.intimp.2015.10.002
• Publication Date: 2015-10-26T05:33:45Z
• 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
• Keywords: Inflammation; Lipopolysaccharides; 0301 basic medicine; Dose-Response Relationship, Drug; Foot; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Plant Roots; 3. Good health; Mice; 03 medical and health sciences; RAW 264.7 Cells; Animals; Cytokines; Edema; Oleanolic Acid; Clematis; Skin

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.