Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and in rat arthritis models.
BACKGROUND
The objective of this study was to determine the anti-inflammatory, nociceptive, and antiarthritic effects of piperine, the active phenolic component in black pepper extract.


METHODS
The in vitro anti-inflammatory activity of piperine was tested on interleukin 1beta (IL1beta)-stimulated fibroblast-like synoviocytes derived form patients with rheumatoid arthritis. The levels of IL6, matrix metalloproteinase (MMPs), cyclo-oxygenase 2 (COX-2), and prostaglandin E2 (PGE2) were investigated by ELISA and RT-PCR analysis. The analgesic and antiarthritic activities of piperine were investigated on rat models of carrageenan-induced acute paw pain and arthritis. The former were evaluated with a paw pressure test, and the latter by measuring the squeaking score, paw volume, and weight distribution ratio. Piperine was administrated orally to rats at 20 and 100 mg/kg/day for 8 days.


RESULTS
Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE2 in a dose dependant manner at concentrations of 10 to 100 microg/ml. In particular, the production of PGE2 was significantly inhibited even at 10 microg/ml of piperine. Piperine inhibited the migration of activator protein 1 (AP-1), but not nuclear factor (NF)kappaB, into the nucleus in IL1beta-treated synoviocytes. In rats, piperine significantly reduced nociceptive and arthritic symptoms at days 8 and 4, respectively. Histological staining showed that piperine significantly reduced the inflammatory area in the ankle joints.


CONCLUSIONS
These results suggest that piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Thus, piperine should be further studied with regard to use either as a pharmaceutical or as a dietary supplement for the treatment of arthritis.
Bang
Jun Soo
JS
East-West Bone & Joint Research Institute, East-West Neo Medical Center, Kyung Hee University, Gangdong-gu, Seoul, Republic of Korea.
Oh
Da Hee
DH
Choi
Hyun Mi
HM
Sur
Bong-Jun
BJ
Lim
Sung-Jig
SJ
Kim
Jung Yeon
JY
Yang
Hyung-In
HI
Yoo
Myung Chul
MC
Hahm
Dae-Hyun
DH
Kim
Kyoung Soo
KS