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eCAM Advance Access published online on June 8, 2006

eCAM, doi:10.1093/ecam/nel025
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© The Author (2006). Published by Oxford University Press. All rights reserved.

Original Article

Keishibukuryogan (Gui-Zhi-Fu-Ling-Wan), a Kampo Formula, Decreases Disease Activity and Soluble Vascular Adhesion Molecule-1 in Patients with Rheumatoid Arthritis

Kazuya Nozaki 1, Hiroaki Hikiami 1 *, Hirozo Goto 2, Takako Nakagawa 2, Naotoshi Shibahara 3, and Yutaka Shimada 4

1 Department of Japanese Oriental Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
2 Department of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan
3 Department of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan; 21st Century COE Program, University of Toyama, Toyama, Japan
4 Department of Japanese Oriental Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan; 21st Century COE Program, University of Toyama, Toyama, Japan

* To whom correspondence should be addressed.
Hiroaki Hikiami, E-mail: ami3{at}med.u-toyama.ac.jp


   Abstract

An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS28). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1{beta}, IL-6 and TNF-{alpha}) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS28 decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients.

Keywords: antioxidant; lipid peroxide; vascular cell adhesion molecule-1.
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