Effect and mechanism of sinomenine on the signal transduction of the synovial cell nuclear factor-KB in rats with adjuvant arthritis

Yongfei FANG; Yong WANG; Xin ZHOU; Bing ZHONG; Ganping BAI; Chun ZHANG

ABSTRACT

BACKGROUND:

Sinomenine is an alkaloid monomer extracted from a Chinese medicinal herb sinomenium acutum stem. It is used in the therapy of the rheumatoid arthritis and has clear and definite therapeutic effects, but the therapeutic mechanism is unclear.

OBJECTIVE:

To observe the effect of sinomenine at different doses in vitro on the activity of nuclear factor-κB(NF-κβ) and mRNA expressions of the tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) andinterleukin-10 (IL-10) in the synovial cells of the rats with adjuvant arthritis(AA) to explore the probable mechanism of sinomenine in the treatment of rheumatoid arthritis(RA).

DESIGN:

A controlled repeated measuring study based on the cells.

SETTING:

Department of traditional chinese medicine and the institute of burn research of a military medical university.MATERIALS This study was finished at the Laboratory of the Institute of Burn Research of Chinese PLA. The experimental animals were 25 healthy male Wistar rats of clean grade. The AA model rats were made and the synovial cells were collected and grouped as follows normal control group, AA group,AA + sinomenine 30 mg/L group, AA + sinomenine 60 mg/L group, AA + sinomenine 120 mg/L group. The activity of the NF-κB was measured by the electrophoresis mobility shift assay(EMSA) . The mRNA expressions of the TNF-α, IL-1β and IL-10 were measured by reverse transcription-PCR assay.MAIN OUTCOME

MEASURES:

The results of the changes of the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells of the rats with adjuvant arthritis after the treatment with sinomenine at different doses.

RESULTS:

Compared with the normal control group, the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells in the AA group all increased significantly and the outcomes were 17±6, 0.570±0.047, 0.730±0.093, 0. 683 ±0.081 (t= 2.71 -4.07, P < 0.05). After the administration of sinomenine, the activity of NF-κB showed a good correlation with mRNA expressions of the TNF-αandIL-13(r=0.810, P <0.001; r=0.562, P <0.05), but no statistical relevance with mRNA expression of IL-10 was established. Sinomenine showed a dose-dependent inhibition on the activity of the NF-κB and the mRNA expressions of the TNF-α and IL-1β in a certain range of concentrations(30-120 mg/L), but no dose-dependent inhibition on mRNA expression of the IL-10 was observed.

CONCLUSION:

Through the inhibition of the activity of the NF-κB,sinomenine decreased the mRNA expressions of the TNF-α and the IL-1β in the synovial membrane cells.