Anti-inflammatory effects of BT-201, an n-butanol extract of Panax notoginseng, observed in vitro and in a collagen-induced arthritis model.
OBJECTIVE
Although there has been some success with protein-based anti-tumor necrosis factor alpha (TNF-alpha) therapeutics, the problems associated with protein-based drugs demand alternative approaches. We screened various herbal extracts for their ability to inhibit TNF-alpha secretions and found that BT-201, an n-butanol extract of Panax notoginseng (Burk.) F. H. Chen (P. notoginseng) has such an ability.


METHODS
The purpose of this study has been to evaluate the anti-inflammatory and anti-rheumatic effects of BT-201. The anti-inflammatory effects were evaluated by measuring the effects of BT-201 on the production of TNF-alpha, interleukin (IL)-1beta, inducible nitric oxide (iNO), and matrix metalloproteinase-13 (MMP-13), in vitro. The anti-rheumatic effects were evaluated by treating mice with collagen-induced arthritis (CIA) using a daily oral administration of BT-201 at 15 mg/kg/day. In addition, the effects on NF-kappaB and mitogen-activated protein kinase (MAPK) pathways were evaluated by Western blotting using phospho-specific antibodies.


RESULTS
BT-201 significantly inhibited all the inflammatory parameters evaluated in vitro and delayed the onset and progression of CIA. BT-201 inhibited the activation of NF-kappaB, ERK, p38, and JNK pathways.


CONCLUSIONS
Our results demonstrated that BT-201 can modulate various aspects of inflammation in vitro and that it has disease-modifying, anti-rheumatic effects in vivo, suggesting that it can be a potential alternative to the current anti-TNF-alpha therapeutics for rheumatoid arthritis and other inflammatory disease.
Chang
Sun-Hwa
SH
Department of Pharmacology and Mechanism, Oscotec Inc., 2-17, Omok-ri, Seonggeo-eup, Cheonan, Choongnam, Republic of Korea. sunhwa@oscotec.com
Choi
Youngnim
Y
Park
Jung-Ae
JA
Jung
Dong-Sik
DS
Shin
Jieun
J
Yang
Ji-Hyun
JH
Ko
Seon-Yle
SY
Kim
Se-Won
SW
Kim
Jung-Keun
JK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy; D002478:Cells, Cultured; D003094:Collagen / Q000633:toxicity; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D009569:Nitric Oxide / Q000378:metabolism*; D053723:Panax notoginseng / Q000737:chemistry; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; C519374:Panax notoginseng extract; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003094:Collagen; D053509:Matrix Metalloproteinase 13