Sakaguchi S, Furusawa S, Yokota K, Sasaki K, Takayanagi M, Takayanagi Y
First Department of Hygienic Chemistry, Tohoku College of Pharmacy, Sendai, Japan.
Biol Pharm Bull. 1996 Nov;19(11):1474-8. doi: 10.1248/bpb.19.1474.
The effects of a traditional Chinese medicine Sho-saiko-to (Kampo prescription) were investigated on the various metabolic disorders and antitumor activity of recombinant human tumor necrosis factor (rhTNF) administered to mice. The glycogen level in liver of rhTNF (5 x 10(4) units/mouse, i.v.)-injected mice was markedly lower at 4 h post-intoxication than that in the control, whereas the administration of rhTNF to Sho-saiko-to (500 mg/kg/d, p.o.)-pretreated mice resulted in a greater level of glycogen than that in rhTNF alone-treated mice. In mice pretreated with Sho-saiko-to, the level of fibrinogen 4 h after rhTNF injection markedly increased as compared to that in mice treated with rhTNF alone. We also estimated the NO2 in murine macrophage cell line J774A.1 using mice serum after administration of Sho-saiko-to. Our results clearly demonstrated that J774A.1 cells stimulated with endotoxin (1 micrograms/ml) and rhTNF (1 x 10(4) units/ml) can effectively produce nitric oxide (NO), and ascertained the suppressive effect of Sho-saiko-to (500 mg/kg/d, p.o)-pretreated serum on NO generation by endotoxin/TNF-activated J774A.1 cells. When the cells were incubated with endotoxin/TNF and Sho-saiko-to pretreated serum (10-100 microliters), the NO level was significantly lower than that in control serum incubated with endotoxin/TNF alone. The effect of Sho-saiko-to (1 and 10 micrograms/ml) on in vitro cytotoxicity by rhTNF in Meth-A Sarcoma cells was observed to be in a dose dependent fashion. In addition, there was a remarkable enhancement of antitumor activity of rhTNF by Sho-saiko-to pretreatment in mice. These findings suggest that the Kampo prescription Sho-saiko-to may protect mice from severe shock syndrome by rhTNF, and that it may enhance rhTNF-induced activity.
研究了中药小柴胡汤（汉方制剂）对给小鼠注射重组人肿瘤坏死因子（rhTNF）所致的各种代谢紊乱和抗肿瘤活性的影响。rhTNF（5×10⁴单位/小鼠，静脉注射）注射小鼠在中毒后4小时肝脏中的糖原水平明显低于对照组，而给小柴胡汤（500毫克/千克/天，口服）预处理的小鼠注射rhTNF后，糖原水平高于单独注射rhTNF的小鼠。在用小柴胡汤预处理的小鼠中，rhTNF注射后4小时纤维蛋白原水平与单独注射rhTNF的小鼠相比明显升高。我们还在给予小柴胡汤后，用小鼠血清评估了鼠巨噬细胞系J774A.1中的NO₂。我们的结果清楚地表明，用内毒素（1微克/毫升）和rhTNF（1×10⁴单位/毫升）刺激的J774A.1细胞可有效产生一氧化氮（NO），并确定了小柴胡汤（500毫克/千克/天，口服）预处理血清对由内毒素/TNF激活的J774A.1细胞产生NO的抑制作用。当细胞与内毒素/TNF和小柴胡汤预处理血清（10 - 100微升）一起孵育时，NO水平明显低于仅与内毒素/TNF孵育的对照血清。观察到小柴胡汤（1和10微克/毫升）对rhTNF在Meth - A肉瘤细胞中的体外细胞毒性作用呈剂量依赖性。此外，小柴胡汤预处理可显著增强rhTNF在小鼠中的抗肿瘤活性。这些发现表明，汉方制剂小柴胡汤可能保护小鼠免受rhTNF引起的严重休克综合征，并且可能增强rhTNF诱导的活性。
