Antinociceptive Effect of Single Components Isolated from Agrimonia pilosa Ledeb. Extract

Jing Hui Feng,Jeon Sub Jung,Hee Jung Lee,Set Byeol Kim,Hong Won Suh,Soon Sung Lim

doi:10.3390/scipharm87030018

Abstract

Agrimonia pilosa Ledeb. produces an antinociceptive effect in ICR mice in both chemically induced and thermal pain models. In the present study, we examined the antinociceptive effects of single components isolated from Agrimonia pilosa Ledeb. (AP) extract in ICR mice. Three active compounds isolated from AP, including rutin, luteolin-7-O-glucuronide, and apigenin-7-O-glucuronide, were isolated and identified by comparing EI-MS, 1H-, 13C-NMR, and UV. We studied the antinociceptive effects of three single components administered orally at doses of 10 and 20 mg/kg in monosodium urate (MSU)-treated pain model as measured by von Frey test. Among these compounds, apigenin-7-O-glucuronide was more effective in the production of antinociceptive effects. We further characterized the antinociceptive effects and possible mechanisms of apigenin-7-O-glucuronide in writhing and formalin tests. Oral administration of Apigenin-7-O-glucuronide caused a reduction in the number of writhing and effectively reduced the pain behavior observed during the second phase of the formalin test in a dose-dependent manner. In addition, the pretreatment of yohimbine instead of naloxone or methysergide attenuated apigenin-7-O-glucuronide-induced antinociception in the writhing test. Moreover, apigenin-7-O-glucuronide caused reduction in the expression of p-P38, p-CREB, and p-mTOR induced by formalin injection. Our results indicate that apigenin-7-O-glucuronide shows an antinociceptive effect in various pain models. In addition, spinal α2-adrenergic receptors appear to be involved in the production of antinociception induced by apigenin-7-O-glucuronide. Furthermore, the antinociceptive effect of apigenin-7-O-glucuronide appears to be mediated by reduction in the expression of p-P38, p-CREB and p-mTOR levels in the spinal cord.

Highlights

Agrimonia pilosa Ledeb. (AP) is a flowering plant in the Rosacea family; it has been used traditionally for the treatment of abdominal pain, sore throat, headaches, bloody discharge, parasitic infections, and eczema in Korea and other Asian countries [1]
We have previously reported that AP extract produces a significant antinociceptive effect in chemically induced pain models, such as writhing and formalin tests as well as thermal pain models such as tail-flick and hot-plate tests, indicating the AP extract alleviate chemical and thermal nociception [11]
We have shown AP extract is effective in relieving the pain in writhing and formalin tests, it has not been well characterized which components are responsible for the production of antinociception

Summary

Introduction

Agrimonia pilosa Ledeb. (AP) is a flowering plant in the Rosacea family; it has been used traditionally for the treatment of abdominal pain, sore throat, headaches, bloody discharge, parasitic infections, and eczema in Korea and other Asian countries [1]. We have previously reported that AP extract produces a significant antinociceptive effect in chemically induced pain models, such as writhing and formalin tests as well as thermal pain models such as tail-flick and hot-plate tests, indicating the AP extract alleviate chemical and thermal nociception [11]. We found that the antinociceptive effect induced by AP extract appears to be mediated. We have shown AP extract is effective in relieving the pain in writhing and formalin tests, it has not been well characterized which components are responsible for the production of antinociception. The present study was designed to examine the possible effects of several single components isolated from AP extract in various pain models

Results

Discussion

Conclusion