The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models

Journal of Pharmacy and Pharmacology - Tập 60 Số 10 - Trang 1347-1354 - 2010
Suk-Yun Kang1, Seo‐Yeon Yoon1, Dae‐Hyun Roh1, Mi‐Jeong Jeon2, Hyoung‐Sig Seo1, Dong-Kyu Uh1, Young‐Bae Kwon3, Hyun‐Woo Kim4, Ho Jae Han5, Hye‐Jung Lee6, Jang‐Hern Lee1
1Department of Veterinary Physiology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea
2R&D Center, Daewoong Pharmaceutical Company, Yongin, South Korea
3Department of Pharmacology, Institute for Medical Science, Chonbuk National University Medical School, Jeonju, South Korea
4Department of Physiology, College of Medicine and Research Institute for Medical Sciences, Chungnam National University, Daejeon, South Korea
5Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwang-ju, South Korea
6[Acupuncture & Meridian Science Research Center, Kyung Hee University, Seoul, South Korea]

Tóm tắt

Abstract 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 (PGE2) 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 PGE2 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.

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