Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice.
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.
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.
Chul Won
CW
Lee
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
Sang Mi
SM
Park
Department of Pharmacology, Mudanjiang Medical University, Mudanjiang 157011, China. Electronic address: zhao_rongjie@yahoo.com.
Rongjie
R
Zhao
Aquaculture Industry Division, NFRDI, Gangneung, South Korea.
Chu
C
Lee
Institute of Marine BioTechnology, Pusan National University, Busan 609-735, South Korea.
Wonjoo
W
Chun
Institute of Marine BioTechnology, Pusan National University, Busan 609-735, South Korea.
Yonghae
Y
Son
Dept. of Oriental Cuisine and Culinary Art, Yongsan University, Yangsan 626-870, South Korea.
Sung Hun
SH
Kim
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
Ji Yun
JY
Jung
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
Kyung Hwan
KH
Jegal
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
Il Je
IJ
Cho
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
Sae Kwang
SK
Ku
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea.
Young Woo
YW
Kim
Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan 680-749, South Korea.
Seong A
SA
Ju
MRC-GHF, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, South Korea. Electronic address: sckim@dhu.ac.kr.
Sang Chan
SC
Kim
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: wgan@pusan.ac.kr.
Won G
WG
An
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D039324:Clematis / Q000737:chemistry*; D016207:Cytokines / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005528:Foot / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D000067996:RAW 264.7 Cells; D012867:Skin / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; D009828:Oleanolic Acid; D002351:Carrageenan; C025763:hederagenin
Hederagenin; Histological examination; Inflammatory response; Mouse paw edema; Nuclear factor-kappa B