Araki Ryota, Nishida Shoji, Hiraki Yosuke, Li Feng, Matsumoto Kinzo, Yabe Takeshi
Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University.
Biol Pharm Bull. 2016;39(2):289-94. doi: 10.1248/bpb.b15-00707.
Sickness behavior is a series of behavioral and psychological changes that develop in those stricken with cancers and inflammatory diseases. The etiological mechanism of sickness behavior is not known in detail, and consequently there are no established standard therapies. Kamikihito (KKT), a Kampo (traditional Japanese herbal) medicine composed of 14 herbs, has been used clinically to treat psychiatric dysfunction. Previously, we found that KKT ameliorated sickness behavior in mice inoculated with murine colon 26 adenocarcinoma cells. In this study, we examined the effects of KKT on bacterial endotoxin lipopolysaccharide (LPS)-induced sickness behavior in mice. The administration of LPS caused the emotional aspects of sickness behavior, such as loss of object exploration, social interaction deficit, and depressive-like behavior. LPS also induced mRNA expression for cyclooxygenase (COX)-2, interleukin (IL)-1β and IL-6, and increased the number of c-Fos immunopositive cells in the hypothalamus and amygdala. KKT ameliorated the behavioral changes and reversed the increases in c-Fos immunopositive cells in the two brain regions, but did not influence the mRNA expression. These results suggest that KKT ameliorates sickness behavior via the suppression of neural activation without anti-inflammatory effects, and that KKT has the potential to treat sickness behavior.
疾病行为是癌症和炎症性疾病患者所出现的一系列行为和心理变化。疾病行为的病因机制尚不清楚，因此尚无既定的标准疗法。加味逍遥散（KKT）是一种由14种草药组成的汉方（传统日本草药）药，已在临床上用于治疗精神功能障碍。此前，我们发现KKT可改善接种小鼠结肠26腺癌细胞的小鼠的疾病行为。在本研究中，我们研究了KKT对细菌内毒素脂多糖（LPS）诱导的小鼠疾病行为的影响。LPS的给药导致了疾病行为的情绪方面，如物体探索丧失、社交互动缺陷和抑郁样行为。LPS还诱导了环氧化酶（COX）-2、白细胞介素（IL）-1β和IL-6的mRNA表达，并增加了下丘脑和杏仁核中c-Fos免疫阳性细胞的数量。KKT改善了行为变化，并逆转了两个脑区中c-Fos免疫阳性细胞的增加，但不影响mRNA表达。这些结果表明，KKT通过抑制神经激活改善疾病行为而无抗炎作用，并且KKT具有治疗疾病行为的潜力。
