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

  • Int Immunopharmacol. 2015 Dec;29(2):528-537. doi: 10.1016/j.intimp.2015.10.002.
Chul Won Lee  1 ,  Sang Mi Park  2 ,  Rongjie Zhao  3 ,  Chu Lee  4 ,  Wonjoo Chun  5 ,  Yonghae Son  5 ,  Sung Hun Kim  6 ,  Ji Yun Jung  2 ,  Kyung Hwan Jegal  2 ,  Il Je Cho  2 ,  Sae Kwang Ku  2 ,  Young Woo Kim  2 ,  Seong A Ju  7 ,  Sang Chan Kim  8 ,  Won G An  9
Affiliations
  • 1. Institute of Marine BioTechnology, Pusan National University, Busan 609-735, South Korea; MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
  • 2. MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
  • 3. Department of Pharmacology, Mudanjiang Medical University, Mudanjiang 157011, China. Electronic address: [email protected].
  • 4. Aquaculture Industry Division, NFRDI, Gangneung, South Korea.
  • 5. Institute of Marine BioTechnology, Pusan National University, Busan 609-735, South Korea.
  • 6. Dept. of Oriental Cuisine and Culinary Art, Yongsan University, Yangsan 626-870, South Korea.
  • 7. Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan 680-749, South Korea.
  • 8. MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea. Electronic address: [email protected].
  • 9. Institute of Marine BioTechnology, Pusan National University, Busan 609-735, South Korea; Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 626-870, South Korea. Electronic address: [email protected].
PMID: 26481049 DOI: 10.1016/j.intimp.2015.10.002
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.

Keywords
Hederagenin; Histological examination; Inflammatory response; Mouse paw edema; Nuclear factor-kappa B.
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