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.

Low-frequency electroacupuncture suppresses carrageenan-induced paw inflammation in mice via sympathetic post-ganglionic neurons, while high-frequency EA suppression is mediated by the sympathoadrenal medullary axis.

Although the frequency-dependent antinociceptive mechanisms of electroacupuncture (EA) have been well demonstrated, the anti-inflammatory mechanisms that underlie the suppressive effects induced by different frequencies of EA stimulation on peripheral inflammation are largely unknown. We have previously reported that EA stimulation can activate the sympathetic nervous system (SNS) and that this activation is responsible for the EA-induced suppression of zymosan-induced leukocyte migration. The present study was designed to evaluate the differential effect of low (1Hz, LF EA) versus high (120Hz, HF EA) frequency EA stimulation on SNS activation and ultimately on carrageenan-induced inflammation. Immediately after carrageenan injection, we applied either LF EA or HF EA bilaterally to the Zusanli (ST36) acupoints. To evaluate the anti-inflammatory effect of EA (EA-AI), paw volume and myeloperoxidase (MPO) activity, a marker of infiltrated leukocytes, were measured and the paw withdrawal latency to noxious heat stimulation was also assessed. Both LF EA and HF EA significantly suppressed the carrageenan-induced paw edema and MPO activity. Moreover, thermal hyperalgesia was strongly attenuated in both the LF EA and HF EA groups. Adrenalectomy significantly diminished HF EA-AI without affecting LF EA-AI. Pretreatment with the corticosterone receptor antagonist, RU-486 did not affect either LF EA- or HF EA-AI. On the other hand, administration of 6-hydroxydopamine (a neurotoxin for peripheral sympathetic nerve endings) selectively blocked LF EA-AI. Propranolol (a beta-adrenoceptor antagonist) completely abolished both LF EA- and HF EA-AI. The results of this study suggest that the suppressive effects of LF EA on carrageenan-induced paw inflammation are mediated by sympathetic post-ganglionic neurons, while the suppressive effects of HF EA are mediated by the sympatho-adrenal medullary axis.