The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models.
Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25-200 mg kg(-1)) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE(2)) production in the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg(-1) in the zymosan experiment, we used this dose of UA in a subsequent study using an adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg(-1), per oral, once a day for 10 days) was started from day 12 after adjuvant injection. UA dramatically inhibited paw swelling, plasma PGE(2) production and radiological changes in the joint caused by CFA injection. Moreover, UA significantly suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as the spinal Fos expression, as determined by immunohistochemistry, which was increased by CFA injection. In addition, overall anti-arthritic potency of UA was comparable with ibuprofen (100 mg kg(-1), oral) while UA did not induce significant gastric lesions as compared with the ibuprofen treatment group. These findings strongly suggest that UA is a useful suppressive compound for rheumatoid arthritis treatment with low risk of gastric problems.
Kang
Suk-Yun
SY
Department of Veterinary Physiology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea.
Yoon
Seo-Yeon
SY
Roh
Dae-Hyun
DH
Jeon
Mi-Jeong
MJ
Seo
Hyoung-Sig
HS
Uh
Dong-Kyu
DK
Kwon
Young-Bae
YB
Kim
Hyun-Woo
HW
Han
Ho-Jae
HJ
Lee
Hye-Jung
HJ
Lee
Jang-Hern
JH
D000208:Acute Disease; D000818:Animals; D018501:Antirheumatic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D002908:Chronic Disease; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D032067:Oldenlandia / Q000737:chemistry; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000737:chemistry / Q000627:therapeutic use*; D015054:Zymosan; D000097245:Ursolic Acid
D018501:Antirheumatic Agents; D015232:Dinoprostone; D010936:Plant Extracts; D014315:Triterpenes; D015054:Zymosan; D000097245:Ursolic Acid