Ono Yuka, Inoue Makoto, Mizukami Hajime, Ogihara Yukio
Laboratory of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Biol Pharm Bull. 2004 Sep;27(9):1406-13. doi: 10.1248/bpb.27.1406.
Kanzo-bushi-to (KBT) is a traditional Japanese herbal medicine (Kampo medicine), which is used in Japan to treat rheumatoid arthritis. In the present study, we investigated the suppressive effect of KBT on collagen-induced arthritis (CIA) and further studied the underlying mechanism. CIA was induced in male DBA/1J mice by immunization with bovine type II collagen, followed by a booster injection 21 d later. KBT was given at a dose of 430 mg/kg/d from three days before the first immunization to the end of the experiment. KBT suppressed CIA development effectively and further protected focal bone erosion and bone destruction as evidenced by the reduced histological score. Histochemical examination revealed that KBT decreased TRAP-positive cells at the synovium-bone interface and at the sites of focal bone erosion, coincident with the findings that RANKL/OPG mRNA ratio was significantly reduced by KBT treatment. KBT also decreased mRNA levels of M-CSF and iNOS in joints and of iNOS in peritoneal macrophages. In conclusion, KBT prevented osteoclast generation by decreasing RANKL/OPG ratio and M-CSF mRNA levels, resulting in reduction in bone erosion and destruction. In addition, KBT has anti-inflammatory effect such as the suppression of iNOS expression in peritoneal macrophages and joints of CIA mice. These finding suggests that KBT is a potential new therapeutic agent for the treatment of RA.
汉方风湿汤（KBT）是一种传统的日本草药 medicine（汉方 medicine），在日本用于治疗类风湿性关节炎。在本研究中，我们研究了KBT对胶原诱导性关节炎（CIA）的抑制作用，并进一步研究了其潜在机制。通过用牛II型胶原免疫雄性DBA/1J小鼠诱导CIA，21天后进行加强注射。从首次免疫前三天至实验结束，以430mg/kg/d的剂量给予KBT。KBT有效抑制了CIA的发展，并进一步保护了局部骨侵蚀和骨破坏，组织学评分降低证明了这一点。组织化学检查显示，KBT减少了滑膜-骨界面和局部骨侵蚀部位的TRAP阳性细胞，这与KBT治疗使RANKL/OPG mRNA比值显著降低的结果一致。KBT还降低了关节中M-CSF和iNOS的mRNA水平以及腹腔巨噬细胞中iNOS的mRNA水平。总之，KBT通过降低RANKL/OPG比值和M-CSF mRNA水平来防止破骨细胞生成，从而减少骨侵蚀和破坏。此外，KBT具有抗炎作用，如抑制CIA小鼠腹腔巨噬细胞和关节中iNOS的表达。这些发现表明KBT是一种治疗RA的潜在新治疗剂。
